WHAT EVERY PROFESSIONAL WORKING IN PALLIATIVE CARE … · 2013. 1. 13. · age, or described in terms of such damage”(2) relates better to Palliative Care, on which dai-ly practice

INTRODUCTION

From all dimensions and symptoms thatmakes difficult to live with cancer, Pain isprobably the most unpleasant and detri-mental symptom for the quality of life.Whether it is in the active or palliative treat-ment phase, or if the patient is a Cancer sur-vivor, no single achievement in the re-struc-tured life of these patients after their diag-nosis is made can be enjoyable if uncon-trolled Pain is present.

The pourpose of this paper is to present a

wide scope of our current view of the general

context, ethiology, mechanisms, and the treat-

ment approaches from the basis to the most

refined and updated interventions in order to

control cancer pain. Its relation to decision-

making in palliative care is remarked when

feasible, and the final target is to serve as a ref-

erence paper for the non-pain specialist in a

daily multidimensional practice towards qual-

ity of life improvement in patients remarkably

associated with severe pain.

Cancer pain is defined as pain that is attrib-

utable to cancer or its therapies(1). The more

general and accepted definition of pain as “an

unpleasant sensory and emotional experience

associated with actual or potential tissue dam-

Resumen

El cuidado paliativo y el manejo del dolorestán profundamente unidos en la práctica dia-ria. La actualización de los conocimientos fun-damentales acerca del estado actual de losconceptos y técnicas para el manejo de lospacientes con Cáncer es de una enorme impor-tancia para todos los profesionales que mane-jan este tipo de pacientes, tanto como fuentede información como de soluciones a sus pro-blemas. El dolor agudo y crónico ocurre congran frecuencia en los pacientes con cáncer,por lo cual la evaluación y el tratamientoinadecuados puede interferir con el tratamien-to antitumoral y deteriorar su calidad de vida.Mientras que el control del dolor es importan-te independiente del estado de la enfermedad,se convierte en una prioridad en pacientes conestados avanzados de la enfermedad y que noson candidatos para terapias potencialmentecurativas bajo el espectro de un cuidado palia-tivo integral.

Palabras clave: dolor, cáncer, evaluación deldolor, tratamiento del dolor en cáncer, cuidadospaliativos.

Abstract

Palliative care and pain management areclosely bounded to everyday practice.

A basic knowledge update about thecurrent status of concepts and techniques forCancer pain management is of enormousimportance for every pactioner caring forCancer patients as a resource for appropiateinformation and solution to their pain pro-blems. Acute and chronic pain occurs in a highfrequency in Cancer patients. Inadequateassessment and treatment of pain and otherdistressing symptoms may interfere with pri-mary antitumor therapy and markedly detractfrom their quality of life . While a strong focuson pain control is important independent ofdisease stage, it is a special priority in patientswith advanced disease who are no longer can-didates for potentially curative therapy underthe scope of an integral perspective to pallia-tive care.

Key word: pain, cancer, pain assessment,pain cancer treatment, palliative care.

WHAT EVERY PROFESSIONAL WORKING IN PALLIATIVE CARESHOULD KNOW ABOUT CANCER PAIN MANAGEMENT

Allen W. Burton* and Pedro F. Bejarano***Section Chief Cancer Pain Management. Department of Anesthesiology. UTMD Anderson Cancer Center.

**Private Practice Associates. Madrid, Spain.

PSICOONCOLOGÍA. Vol. 1, Núms. 2-3, 2004, pp. 57-90

Corresponding Author Address:

Pedro F. BejaranoApartado de Correos 613428080 MadridE-mail: [email protected]

age, or described in terms of such damage”(2)

relates better to Palliative Care, on which dai-ly practice every symptom is deeply influencedby the context, the expectations and all type ofemotional experiences of the cancer patient.Cancer pain is a problem that has attained arising level of recognition among the healthcare community. Optimal managementinvolves careful assessment, optimal analge-sia, intensive follow-up and a proactiveapproach to treatment. Adequate control ofpain can be achieved in the majority of patientswith a rigorous and aggressive application of atreatment algorithm that is ultimately quitestraightforward(3, 4). Control of pain and relatedsymptoms promotes an enhanced quality oflife, improved functioning, better complianceand a means for patients to focus on thosethings that give meaning to life(5). In addition totheir salutary effects on quality of life, mount-ing evidence suggests that good pain controlinfluences survival(6,7).

Approximately 6.35 million new cases ofcancer are diagnosed worldwide annually,half of which originate in developingnations(8). The WHO estimates that by theyear 2021, there will be 15 million new ca-ses of cancer worldwide annually. This willlead to cancer patients living longer withpain due to cancer disease itself and withtherapy, which brings the need for a bettersymptom control in extreme situations bothfor pain and for other symptoms in PalliativeCare. Approximately 1.04 million new diag-nosis of cancer are made annually in theUnited State alone(9). One of every five deathin the United States is a result of cancer,which is approximately 1400 cancer relateddeath daily(10). The incidence of cancerincreases with age and is particularly prob-lematic given our rapidly aging population.It is estimated that up to 50% of patientsundergoing treatment for cancer and up to90% of patients with advanced cancer havepain(11). Most (70%) cancer pain is due totumor involvement of organic structures,notably bone, neural tissue, viscera, or oth-ers. Up to 25% of cancer pain is due to ther-apy, including chemotherapy, radiotherapy,or surgery. Up to 10% of “cancer pain” is

accounted for by common chronic pain syn-dromes, including back pain and headaches,which might have been exacerbated by theongoing growth or treatment of cancer(12).

Overall, cancer cure rates have notchanged markedly over the past 4 decades:the overall 5-year survival rate for patientsdiagnosed with cancer in United States is stillonly about 40 to 50 %(13) and as a result ofinadequate early detection, is less than onethird worldwide(8). The annual mortality rateis about 4.3 million worldwide and about510,000 in the United States(9). Palliativetreatment, which may extend survival, is oftenmore successful than therapies with curativeintent, and as a result, there is an increasingnumber of patients to bearing advanced dis-ease with associated chronic pain. Further-more, the last decades advances in cancertreatment has increased not only the lifeexpectancy but the number of survivors of aonce fully mortal disease, increasing also thenumber of patients residual pain from cancertreatment that needs palliative treatment.

CANCER PAIN STATISTICS

Together with anorexia and fatigue, painis among the most common symptom associ-ated with cancer(14,15). Significant pain is pres-ent in up to 25% of patients in active treat-ment and in up to 90% of patients withadvanced cancer(11, 16 -20). According to sever-al studies including a survey of oncologists inthe Eastern Cooperative Oncology Group(ECOG) and a survey of 1103 consecutiveadmission to a U.S tertiary care cancer hospi-tal, 73% of patients in active treatment admi-tted to pain with 38 % reporting severepain(21). Despite the availability of simple,cost-effective treatment(22), inadequately con-trolled pain remains a significant problem.

Studies following the WHO cancer painladder (e.g. oral analgesics and careful fol-low-up) have achieved favorable outcomesin the 70 to 90 % range(23) suggesting that thekey to achieving more effective global can-cer pain relief involves applying known tech-nology more effectively rather than develop-ment of new medical technologies or drugs.

58 Allen W. Burton and Pedro F. Bejarano

While a variety of such factors have beenidentified, authorities agree that so-called“opiophobia”, a reluctance to use opioids,largely because of exaggerated concerns ofaddiction and regulatory reprisal, exerts apotent influence at all levels and probably isthe single most important impediment to bet-ter symptom control globally. In general, inWestern developed sectors, barriers arelargely educational and attitudinal in nature,while in developed nations a multitude ofresource and access problems are operant.As an example, negative indirect effects onsurvival may stem from the negative influ-ence of pain on performance status. Whenperformance status is low, as is often the casewhen pain is severe, patients may find it dif-ficult to tolerate recommended chemothera-py, indeed they may not be considered can-didates for chemotherapy. Further benefits ofgood pain management often includeimprovements in nutrition, rest and mood, allof which contribute to quality of life and havethe potential to influence the outcome ofantineoplastic therapy.

EVALUATION AND ASSESSMENT

Pain is always subjective and is experi-enced only by the patient. Over the past 20years, the assessment of pain has been thesubject of much research and refinement oftechniques and instruments, from which themost relevant are described below:

Many pain clinics utilize a question-naire to aid in and standardize assessment.The Wisconsin Brief Pain Inventory(BPI)(24,25) and Memorial pain assessmentcard(26) are well accepted and standard toolsfor assessing cancer pain. At The Universi-ty of Texas MD Anderson Cancer Center, aninstitutionally approved MD Andersonquestionnaire (modified BPI) is used for ini-tial and follow-up assessment of patients.

Numerous tools are available for assess-ing cancer related pain including:

1. Wisconsin Brief Pain Inventory: a. 15-minute questionnaire, which can

be self-administered.

b. Includes several questions about thecharacteristics of pain, including its ori-gin and their effects of prior treatments.

c. It incorporates two valuable featuresof the McGill Pain Questionnaire, agraphic representation of the loca-tion of pain and groups of qualitativedescriptors. Severity of pain isassessed by a series of VAS that scorepain at its best, worst and on aver-age. The perceived level of interfer-ence with normal function is quanti-fied with VAS also.Preliminary evidence suggests thatthe BPI is cross-culturally valid(24,25)

and is useful, particularly whenpatients are not fit to complete amore through or comprehensivequestionnaire.

2. Memorial Pain Assessment Card:a. It is a simple efficient, and valid

instrument that provides rapid clini-cal evaluation of the major aspectsof pain experienced by cancerpatients(26).

b. It is easy to understand and use andcan be completed by experiencepatients in 20 seconds.

c. It consists of two-sided 8.5x11 inchcard that is folded so that four sepa-rate measures are created.

d. It features scales, intended for themeasurements of pain intensity, painrelief, mood and a set of descriptiveadjectives.

3. Edmonton Staging System:a. It is performed by health care

providers

b. It was developed to predict the like-lihood of achieving effective relief ofpain in cancer patients(27,28).

c. The system’s originators have provid-ed validation that treatment outcomecan be accurately predicted accord-ing to five clinical features (Neuro-pathic pain, movement-related pain,recent history of tolerance to opioids,

What every professional working in palliative care should know about cancer pain management 59

psychological distress, and a historyof alcoholism or drug abuse).

d. Staging requires only 5-10 minutesand requires no special skills.

e. Its value lies in prospective identifica-tion of potentially problematic patients,further legitimizing clinical research onsymptom control by introducing betterstandardization and improving ourability to assess critically the results ofvarious therapeutic interventions inlarge population of patients.

4. Pediatric Cancer Pain Assessment:This includes Beyer’s The Oucher, Eland’s

color scale-body outline, Hester’s poker chiptool, McGrath’s faces scale, and others(29-32).

5. Numerical Pain Rating Scale (NRS) orVisual Analog Scale (VAS):Pain is assessed on an 11 point numeri-

cal rating scale from 0 (no pain) to 10 (worstpain imaginable). The VAS is a 10 cm linewithout markings from no pain to worst pain;the patient marks their pain score and a meas-urement in cm defines their level of pain.

Objective observations of grimacing,limping, and vital signs (tachycardia) may beuseful in assessing the patient, but these signsare often absent in patients with chronic can-cer pain. Pain evaluation should be integra-ted with a detailed oncological, medical, andpsychological assessment. The initial evalua-tion should include evaluation of person, hisor her feelings and attitudes about the painand disease, family concerns and the patient’spre-morbid psychological history. A compre-hensive but objective approach to assessmentgenerates confidence in the patients and fami-ly that will be valuable throughout treatment.

A comprehensive evaluation of thepatients with cancer pain includes the fol-lowing:

1. The chief complaint is obtained toensure appropriate categorization or triage(e.g. severe pain with a bowel obstructionmay need to be sent to the emergency cen-ter for urgent treatment).

2. Next, the oncologic history isobtained to gain the context of the painproblem. The oncologic history includes:diagnosis and stage of disease, therapy andoutcome-including side effects, and thepatient’s understanding of the diseaseprocess and prognosis.

3. The pain history should include anypremorbid chronic pain and for each newpain site must include: Onset and evolution,site and radiation, pattern (constant, inter-mittent, or unpredictable), intensity (best,worst, average, current) 0-10 scales, quali-ty, exacerbating and relieving factors, paininterference with usual activities, neurolo-gical and motor abnormalities (includingbowel and bladder continence), vasomotorchanges, current and past analgesics (use,efficacy, side effects). Prior analgesic use,efficacy, and side effects should be cata-loged. Prior treatments for pain should benoted (radiotherapy, nerve blocks, physio-therapy, etc.)

4. Review of medical record and radi-ological studies: Many of the treatments forcancer can cause pain themselves(chemotherapy, and radiotherapy inducedneuropathies or postoperative pain syn-dromes; post-thoracotomy pain syndromesand post-mastectomy pain syndrome), andmany specific cancers can cause well esta-blished pain patterns due to known likelysites of methastasis as: a) Breast to longbones, spine, chest wall, brachial plexus,and spinal cord, b) Colon to pelvis, hips,lumbar plexus, sacral plexus and spinalcord, c) Prostate to long bones, pelvis, hips,lung and spinal cord.

5. Psychological History: This shouldinclude marital and residential status,employment history and status, educatio-nal background, functional status, activitiesof daily living, recreational activities, su-pport systems, health and capabilities ofspouse or significant other, past history of(or current) drug or alcohol abuse.

6. Medical History (independent ofoncological history) including coexistingsystemic disease, exercise intolerance,allergies to medications and medication


use, prior illness and surgery, and a tho-rough review of systems Including the fol-lowing systems:

a. General (including anorexia, weightloss, cachexia, fatigue, weakness,insomnia)

b. Neurologic (including sedation,confusion, hallucination, heada-che, motor weakness, altered sensa-tion, incontinence)

c. Respiratory (including dyspnea,cough, pneumonia)

d. Gastrointestinal (including dyspha-gia, nausea, vomiting, constipation,diarrhea)

e. Psychological (Including irritability,anxiety, depression, dementia)

f. Genitourinary (including urgency,hesitancy, or hematuria)

7. Physical Examination : The physicalexamination must be thorough although attimes it is appropriate to perform a focusedexamination. In patients with spinal pain,and known or suspected metastatic disease acomplete neurologic exam is mandatory. Adetailed physical examination can find newevidence of metastatic disease in nearly 64%of patients referred to a Pain Service, resul-ting in anti-tumor therapy for 18% of patients.

8. Determination of need for furtherstudies.

9. Formulate clinical impression (diag-nosis by symptom, ethiology,and mecha-nism ). Multiple diagnosis usually apply andit is optimal to use the most specific knowndiagnosis. For example: 1) T-11 compres-sion fracture (pathologic versus osteoporot-ic) with severe pain, 2) Metastatic breastcarcinoma (with known bony metastasis), 3)Nausea with inanition, 4) Constipation.

10. Formulate recommendations (Plan)and alternatives for each problem. For exam-ple (related to the above problem list): 1) MRIof the T-Spine with consideration of vertebro-plasty if appropriate. 2) Oxycodone-slowrelease 10 mg twice daily, with oral transmu-cosal fentanyl citrate for breakthrough pain.3) Management including further chemother-apy, radiotherapy, or bisphosphonates in

coordination with the patient’s oncologist. 4)Metoclopramide 10 mg po 30 min prior tomeals and as needed for nausea. 5) Additionof senekot-S twice daily for constipation.

11. Call oncologist and/or primary careprovider if applicable

12. Exit interview

– Explain the probable cause of symptomsin terms the patient can understand.

– Discuss prognosis for symptom relief,management options and specific re-commendations. In addition to writingprescriptions, oral and written instruc-tions must be provided. Educationalmaterial regarding medications, painmanagement strategies, procedures,or others should be provided. Poten-tial side effects should be discussed.

– Arrange for follow-up with cliniccontact information.

– A dictated summary should be sent toreferring and consulting physicians tokeep them appraised of the patient’spresent status and treatment offered.

DIMENSIONAL CLASSIFICATION OFCANCER PAIN

Chronicity

1. Acute Pain: It is frequently associa-ted with sympathetic hyperactivity andheightened distress(33). It is often temporallyassociated with the onset or recrudescenceof primary or metastatic disease, and itspresence should motivate the clinician toseek its cause aggressively and need formore potent analgesics.

2. Subacute Pain: The pain that somepatients experience for 4-6 weeks after amajor surgical procedure. This type of painis largely under-treated and deserves specialattention as it may affect patient’s ability toperform activities of daily living after dis-charged from the hospital.

3. Chronic Pain: Treating pain of achronic nature mandates a combination ofpalliation, adjustment and acceptance.With time, a biological and behavioral


adjustment to symptoms occurs, and hope-fully associated symptoms are blunted.Chronic pain with superimposed episodesof acute pain (breakthrough pain) is proba-bly the most common pattern observed inpatients with ongoing cancer pain.

Intensity

The consistent use of measurements ofpain intensity aids in following a patient’sprogress and may serve as a basis for inter-patient comparisons. High pain scores mayalert the clinician to the need for moreaggressive treatment (see figure 1. MDACCtreatment algorithm)

Pathophysiology

This approach is useful when formulat-ing the initial approach to treatment.

1. Somatic nociceptive pain is describedas a constant, well-localized pain often cha-racterized as aching, throbbing, sharp or gnaw-ing. It tends to be opioid responsive andamenable to relief by interruption of proximalpathways by neural blockade when indicated.

2. Visceral nociceptive pain originates

from injury to organs. This pain is transmit-ted via fibers in the sympathetic nervous sys-tem(34). Visceral pain is characteristicallyvague in distribution and quality and is oftendescribed as deep, dull, aching, dragging,squeezing or pressure like sensation. Whenacute, it may be paroxysmal and colicky andcan be associated with nausea, vomiting,diaphoresis, and alterations in blood pres-sure and heart rate. Mechanisms of visceralpain include abnormal distension or con-traction of the smooth muscle walls (hollowviscera), rapid capsular stretch (solid vis-cera), ischemia of visceral muscle, serosal ormucosal irritation by algesic substances andother chemical stimuli, distension and trac-tion or torsion on mesenteric attachmentsand vasculature, and necrosis(35) . The vis-cera are, however, insensitive to simplemanipulation, cutting and burning(34). Vis-ceral involvement often produces referredpain(36, 37) (e.g. phrenic nerve-mediatedshoulder pain of hepatic origin).

3. Neuropathic pain is defined as painemanating from the nervous system due toinjury or irritation to some element of thenervous system. Examples of neuropathicpain syndromes associated with cancer aredepicted in Table 1.


Table 1. Examples of Neuropathic Pain Syndromes

Example of Neuropathic Cancer Pain Syndromes

Due to Tumor Growth orHumoral Activity

Due to Surgical Nerve Trauma

Due to Medical Treatment

• Paraneoplastic Polineuropathies

• Brachial Plexus Plexopathy

• Lumbar Plexus Plexopathy

• Skull Base Syndromes

• Spinal Cord Compresion

• Post Thoracotomy Pain

• Post Mastectomy Pain

• Post Amputation /Phantom Pain

• Post Chemotherapy Neuropathies

• Post Irradiation Brachial Plexopathy


Figure 1. MDACC treatment algorithm

Neuropathic pain is often resistant tostandard analgesic therapies and oftenrequires an approach utilizing opioids, anti-convulsants, oral or topical local anesthetics,corticosteroids, NMDA blockers and others.

Temporal aspects of Pain:

1. Constant Pain: This pain is mostamenable to drug therapy administeredaround the clock, contingent on time ratherthen symptoms. It is best managed by long-acting analgesics or in selected cases, infu-sion of analgesics.

2. Breakthrough Pain and Incident Pain:Breakthrough pain that is related to a specif-ic activity, such as eating, defecation, socia-lizing or walking is referred to as incidentpain. Breakthrough pain is best managed bysupplementing the preventative around-the-clock regimen with analgesics with a rapidonset of action and a short duration. Once apattern of incident pain is established, escapeor rescue, doses of analgesics can be admi-nistered in anticipation of the pain provokingactivity. Breakthrough pain that occurs con-sistently prior to the next scheduled dose ofaround-the clock opioids is called “end ofdose failure” and is related to the decrease inplasma concentrations of the analgesicsbelow minimum effective analgesic concen-trations (MEAC). “End of dose failure” is ide-ally managed by increasing the dose of thebasal analgesic or reducing the intervalsbetween doses. Refractory incident painoften is responsive to stabilization, such asfixation of a pathologic fracture or vertebro-plasty for a vertebral compression fracture.

3. Intermittent Pain: This is very unpre-dictable and can be best managed byadministration of immediate release potentanalgesics of rapid onset and short duration.

Specific Cancer Pain Syndromes

1. Osseous invasion or tumor infiltra-tion of the bone is cited as the most com-mon cause of cancer pain and is most oftenseen in metastatic carcinoma of the

prostate, breast, thyroid, lung, or kidney(39-

41). The presentation of bone metastatic painis variable; usually a constant deep dullache, often greatest at night and with move-ment or weight bearing, complicated byparoxysms of stabbing pain. Approximately25% of patients with bone metastasis expe-rience severe pain. Somatic and sympathet-ic fibers carry pain(42,43). A bone scan (Iso-tope Scanning, Scintigraphy) is preferred fordetecting most bone metastasis(39).

Prostaglandin E2 (PGE2) and othercytokines are elaborated by osseous metas-tasis. These cytokines are felt to contributeto pain by sensitization of peripheralperiosteal nociceptors in addition to caus-ing central sensitization. NSAIDs andsteroids are postulated to reduce pain frombony metastasis via inhibition of the cyclo-oxygenase pathway of arachidonic acidbreakdown, thus decreasing the formationof PGE2. The cox-2 selective anti inflamma-tories have been shown in a murine sarco-ma bone metastasis model to effectivelyinhibit spontaneous and movement relatedbone pain, reduce biochemical markers ofperipheral and central sensitization, reducetumor induced osteoclastic proliferation,and finally to reduce overall tumor bur-den(42-44). As deposits enlarge, stretching ofthe periosteum, pathological fracture andperineural invasion contribute to pain andrequirements for analgesics increase. Pallia-tive radiation is commonly successfullyemployed to relieve pain emanating frombony metastasis. Hormonal therapy(chemotherapy such as tamoxifen orleuprolide, orchiectomy, or rarely hypophy-sectomy) often reduces bony pain inpatients with hormonal dependant disease(Breast, Prostate). In general, the hormonerefractory breast and prostatic carcinomasare less responsive to treatment 45,46).

2. Vertebral body metastasis is mostcommonly associated with metastatic carci-noma of the lung, breast and prostate. Local-ized paraspinal, radicular or referred pain isusually the first sign of metastasis to the bonyvertebral column. The pain is often describedas severe local, dull, steady, aching, often


exacerbated by recumbence, sitting, move-ment and local pressure; may be relieved bystanding; local midline tenderness may bepresent; associated nerve compression mayproduce radiating dermatomal pain and cor-responding neurological changes. A specialwarning must be made here to avoid the mostundesirable complication of vertebral bodymetastasis, that can be avoided in most cas-es simply by suspiction and a routinely per-formed neurological examination: an epidur-al-spinal cord compression(47).

3. Base of skull metastasis: Usuallypresent with headache and a spectrum ofneurological findings, especially involvingcranial nerves. Symptomatic metastasis tothe skull is usually - but not always- a latefinding(48). Plain X-ray, Scintigraphy, and CTscan are helpful for diagnosis of bony dis-ease, while MRI and lumbar puncture areuseful to evaluate the soft tissue and to detectleptomeningeal disease, respectively(49).

4. Visceral pain is usually seen in gas-trointestinal malignancies due to directtumor and invasion of visceral structures.This pain is transmitted via fibers in the sym-pathetic nervous system(34). Visceral pain ischaracteristically vague in distribution andquality and is often described as deep, dull,aching, dragging, squeezing or pressure likesensation. When acute, it may be paroxys-mal and colicky and can be associated withnausea, vomiting, diaphoresis, and alter-ations in blood pressure and heart rate.Mechanisms of visceral pain include abnor-mal distension or contraction of the smoothmuscle walls (hollow viscera), rapid capsu-lar stretch (solid viscera), ischemia of viscer-al muscle, serosal or mucosal irritation byalgesic substances and other chemical stim-uli, distension and traction or torsion onmesenteric attachments and vasculature,and necrosis(34,35). Visceral involvementoften produces referred pain(36,37) (e.g.phrenic nerve-mediated shoulder pain ofhepatic origin). The classic cancer visceralpain syndrome is pancreatic cancer relatedpain. This pain is described as relentless,mid-epigastric aching, which radiatesthrough to the mid-back, often relieved by

the fetal position and worsened by recum-bence. These visceral pains can be extraor-dinarily helped with sympathetic visceralneurolytic blockade(50,51).

5. Musculo-skeletal pain is probablyunder diagnosed in cancer patients. Undere-cognition is probably due in part to the inabil-ity of standard radiographic technique to do-cument muscle injury, as well as the varied,sometimes vague, and usually non-neurolog-ical constellation of characteristic symptoms.

6. Nerve invasion: Typically constant,burning dysesthetic pain, often with anintermittent lancinating, electrical compo-nent; may be associated with neurologicdeficit or diffuse hyperesthesia or hypesthe-sia and localized parasthesia; muscle weak-ness and atrophy may be present in mixedor motor nerve syndromes(52-55).

7. Leptomeningeal metastasis, menin-geal carcinomatosis: Most common withprimary malignancies of breast and lung;lymphoma and leukemia; it is secondary todiffuse infiltration of meninges; About 40%of patients have headache or back pain, pre-sumably due to traction on the pain-sensi-tive meninges, cranial, and spinal nervesand/or raised intracranial pressure(56,57).

Headache is most common presentingcomplaint; characteristically unrelenting;may be associated with nausea, vomiting,nuchial rigidity and mental statuschanges(57); associated neurological abnor-malities may include seizures, cranial nervedeficits, papilledema, hemiparesis, ataxiaand cauda syndrome; diagnosis confirmedwith lumbar puncture and CSF analysis,which revealed the presence of malignantcells, and may also be remarkable for anincreased opening pressure, raised protein,and decreased glucose(58). CT or MRI arealso recommended and may reveal plaque-like tumor. The natural history of patientswith leptomeningeal metastasis is gradualdecline and death over 4-6 weeks, althoughsurvival is often extended to 6 months ormore when treatment with radiation thera-py and/or intrathecal chemotherapy is insti-tuted(59). Steroids may be useful in the man-agement of headache(49).


8. Spinal cord compression is usuallyheralded by pain in the presence of neuro-logical changes. An urgent radiologicalwork-up in mandatory in the face of neuro-logical deficits, particularly motor weak-ness, band-like encircling pain or inconti-nence. Prompt treatment in form of radio-therapy or spinal stabilization may limitneurologic morbidity(47) .

9. Plexopathies are syndromes of tumorinvasion into the nerve plexus in the upperof lower extremity. Cervical plexopathy ismost commonly caused by local invasion ofhead and neck cancers or from enlargedlymph nodes. Symptoms are primarily senso-ry in the distribution of plexus, experiencingas aching pre-auricular, post-auricular, orneck pain. Brachial plexopathy is most com-monly due to upper lobe lung cancer (calledthe Pancoast syndrome or superior sulcussyndrome), breast cancer or lymphoma; painis an early symptom, usually preceding neu-rological findings by up to 9 month(52,53), . Thelower cord of the plexus (C8-T1) is affectedmost frequently, and pain is usually diffuseaching in shoulder girdle, radiating downarm, often to the elbow and medial (ulnar)aspect of the hand(54,55). When the uppertrunk is involved (C5-6), pain is usually in theshoulder girdle and upper arm, radiating tothe thumb and index finger. Horner’s syn-drome, dysesthesias, progressive atrophy,and neurological impairment (weakness andnumbness) may occur. In some situations theclinical presentation may be difficult to dif-ferentiate from radiation fibrosis, which cha-racteristically is less severe, less often associ-ated with motor changes, tends to involve theupper trunks, and may be associated withlymphedema(52,60) without a Horner’s sign.Brachial plexus invasion may be associatedwith contiguous spread to the epiduralspace(60-62). Lumbo-sacral plexopathy may bedue to local soft tissue invasion or compres-sion occur most commonly with tumors ofthe rectum, cervix, breast, sarcoma, and lym-phoma; pain is usually the presenting symp-tom in 70% of patients(63); The pain is usual-ly described as aching or pressure-like andonly rarely dysesthetic. Depending on the

level involved, pain is referred to the lowback, abdomen, buttock, or lower extremi-ty(63, 64). Reflex asymmetry and mild sensoryand motor changes when present, were rel-atively early findings, whereas impotenceand incontinence are relatively rare. Thissyndrome must be differentiated from spinalcord invasion or cauda equina syndrome inwhich urgent diagnosis and treatment ismandatory.

10. Chemotherapy Related a. Oral mucositis usually occurs in 1-2

weeks of the initiation of chemother-apy. This condition is most commonwith the use of methotrexate, dox-orubicin, daunorubicin, bleomycin,etoposide, 5-fluorouricil, and dacti-nomycin(65) . Mucositis is often mostsevere when chemotherapy is com-bined with radiation treatments tothe head and neck region.

b. Painful polyneuropathy occurs mostcommonly with vincristine (motor andsensory involvement), vinblastine, tax-ol taxotere, the platinum derivative(predominantly sensory involvement),and navelbine(66); Symptoms com-monly include burning, dysestheticpain in the hands and feet.

11. Post-surgical chronic pain syndromesare most common after mastectomy, thora-cotomy, radical neck dissection, nephrecto-my and amputation(67). The clinical charac-teristics usually include aching, shooting, ortingling pain in distribution of peripheralnerves (e.g. intercostals-brachial, inter-costals, cervical plexus) with or without skinhypersensitivity. In one of the study(68), theincidence of post-mastectomy pain washigher after conservative surgery than modi-fied radical mastectomy (33% versus 17%).In this same study 25 % of patients experi-enced post-operative phantom breast pain.The exact incidence of post-surgical painsyndromes is unclear, but appears to be in the25-50% range by some estimates(67).

12. Headache is present in 60% ofpatients with a primary or metastatic braintumor, half of who classified as their primarycomplaint(69). It is typically steady, deep, dull,


and aching with moderate intensity and that israrely rhythmic or throbbing. It is usually inter-mittent and may be worse in the morning andwith coughing-straining. Symptoms oftenimprove with radiation therapy, non steroidalanti-inflammatories, or corticosteroids(70-72).

13. Cervicofacial pain syndromes aremost common in patients with head andneck cancers. The head and neck are rich-ly innervated by contributions from cranialnerves V, VII, IX, X and upper cervicalnerves, so pain varies in character. Whencranial nerves are involved, symptoms re-present those of trigeminal, glossopharyn-geal, and/or intermittent neuralgia, withsudden, severe lancinating pain radiating tothe face, throat or ear respectively.

14. Radiation therapy may be associatedwith both acute and chronic pain syndromes.Acutely, mucositis, cutaneous burns, may beseen. Chronically, post radiation syndromesinclude osteoradionecrosis, myelopathy,plexopathy, soft-tissue fibrosis, and the emer-gence of new secondary neurogenic tumors.

TREATMENT

The goal of treatment of cancer pain isto relieve pain by modifying its source,interrupting its transmission, or modulatingits influence at brain or spinal cord sites.This can be achieved with various meansand combination of following availablemodalities (see table 2).


(A) Antineoplastic Treatment:

(B) Pharmacological Management 1. NSAID’s2. Opioids 3. Adjuvant analgesics

I. Adjuvant drug trialsII. AntidepressantIII. AnticonvulsantsIV. BaclofenV. Oral local anesthetics

VI. AmphetamineVII. CorticosteroidVIII. N-Methyl-D-Aspartate (NMDA) Antagonists

IX. Alpha-2 Adrenergic antagonistsX. Others

(C) Interventional Pain Management1. Continuous subcutaneous infusion of opioids (CSCI)2. Continuous intravenous infusion of opioids (CII)3. Neuraxial analgesia – epidural or intrathecal indusions4. Neural Blockade Techniques

- Local anesthetic nerve block- Neurolytic nerve block

5. Vertebrosplastia6. Neuromodulation

(D) Behavioral pain management

(F) Home-based and hospice care

Table 2. Treatment modalities available for Cancer Pain patients

Antineoplastic Treatment

The most effective form of treatment ofany cancer related pain is treatment of thecancer itself, which in the majority of caseswill reduce or eliminate the pain. Oncediagnosed, the pathological processresponsible for pain can often be alteredwith surgical extirpation, external beamradiation therapy (targeted fractioned or sin-gle-dosed therapy, hemi body or total bodyirradiation)(73,74), radionuclides (e.g. Stron-tium-89, Samarium) intrarterial chemother-apy(75), hormonal treatment(76) and evenwhole-body hyperthermia(77). The majorityof patients require some form of primaryanalgesic therapy even when pursuing anti-tumor therapy.

Pharmacological Management

The control of pain involves three basicprinciples: modifying the source of the pain,altering the central perception of pain, andblocking the transmission of the pain to thecentral nervous system. In addition, anynew pain in a patient with cancer isassumed disease progression or recurrenceuntil proven otherwise.

Oral analgesics are the mainstay of ther-apy for patients with cancer pain. An esti-mated 70-90% of patients can be renderedrelatively free of pain when straightforwardguidelines-based participles applied in athorough, careful manner (1,3,4,78).

The World Health Organization (WHO)has developed a three-step ladder approachto cancer pain management that reliesexclusively on the administration of oralagents and that is usually effective(19,78). Caremust be taken when use of this ladder, as theevidence was not very strong at the time ofpublication(79), and its use should always beregarded as the pharmachological systemicapproach, usually a part of a more compre-hensive pain control strategy . When thisconservative therapies produce inadequateresults, escalating doses or alternative ther-apy should be sought in the shortest possi-ble time. The role of more invasive forms of

analgesia, ranging from parenteral anal-gesics to neural blockade or neuraxial anal-gesia, should be considered judiciouslythenafter, but never delayed if the cause ofpain is locally restricted(50).

Before initiation of therapy, assessmentof problems and setting realistic goals thatare acceptable to the patient should beestablished along with a treatment plan andcontingencies.

The non-invasive route should be main-tained as long as possible for reasons thatinclude simplicity, maintenance of inde-pendence and mobility, convenience, andcost. Treatment should be directed towardsrelief of pain and suffering, which includesconsideration of all aspects of function (e.g.disturbance of sleep, appetite, mood, activ-ity, posture, and sexuality), and attentionshould be paid not only to physical but alsoto emotional, psychological, and spiritualaspects of suffering.

The University of Texas MD Andersoncancer Center published a modified andcondensed version of the National CancerCenters Network (NCCN) guidelines, thegeneral strategy is of stronger opioids andadjuvants use with more frequent reassess-ment for higher pain levels. Some basicprinciples to manage large population ofpatients are described here as pearls for can-cer pain therapeutics.

1. Nonsteroidal anti-inflammatorydrugs (NSAID’s)

NSAID’s are most effective for pain ofinflammatory (eg. bone metastasis) originby virtue of interference with prostaglandin(PG) Synthesis(80). Consider the regular(around-the-clock) administration of anNSAID as the sole treatment for mild painor in combination with opioid analgesic formoderate or severe pain(1). Potential for ben-efit should be balanced against potential fortoxicity (which includes upper GI irritation,renal insufficiency, platelet dysfunction andmasking of fever), which is pertinent in thecontext of recent antitumor therapy and


advanced age(80). Consider avoidingNSAID’s all together or instituting prophy-laxis (e.g. Misoprostol, and proton pumpinhibitors as Omeprazol ) in patients predis-posed to gastropathy.

The nonacetylated salicylate (sodiumsalicylate, choline magnesium trisalicylate)are associated with a favorable toxicity pro-file, since they fail to interfere with plateletaggregation, are rarely associated with GIbleeding, and are well tolerated by asthmat-ic patients(81,82). A parenteral formulation ofketorolac is equianalgesic to low doses ofmorphine in some settings but is associatedwith the same range of side effects as oralNSAID’s(83).

NSAID’s are associated with s ceilingeffects, above which dose escalations pro-duce toxicity but no greater analgesia. How-ever, the ceiling dose for a given drug differsfrom patient to patient, allowing some poten-tial for dose titration. When efficacy is poor,the clinician may consider rotating to ano-ther NSAID, usually from a different bio-chemical class because it is clear that for agiven patient, clinical response differs amongvarious agents (inter-individual variability),and there is evidence that various classes ofNSAID’s may exert their anti-PG effects ondifferent subtypes of cyclo-oxygenases(COX-1, COX-2)(84), being COX2 the enzymeprimarily responsible for peripheral induc-tion of inflammatory sensitization . and par-tially devoided of the adverse COX1 effectson gastric mucosa, there may be a better safe-ty profile of the newer COX-2 inhibitors incancer patients versus the traditionalNSAIDs, which are non-specific inhibitors ofCOX-1 and COX-2., with potential advan-tage in some type of cancers to reeducetumor burden, but clearly not producing bet-ter analgesia than non selective NSAIDs(85) .

2. Opioids

The so-called “Weak Opioids”:

When NSAID s are not indicated as perthe mechanisms of pain, or if they provideinsufficient relief, are contraindicated, are

poorly tolerated or when pain is severe atpresentation, the addition or substitution ofa so-called “weak” opioid (mostly pro-drugsthat are metabolized by the patient intosmall doses of full opioids e.g. codeine,propoxyphene, hydrocodone, or dihy-drocodone preparations) is recommendedas an analgesic of intermediate potency(1) .These medications are almost exclusivelyformulated as combination products; theseagents are weak only insofar as the inclu-sion of aspirin, acetaminophen, or ibupro-fen results in a ceiling dose above, afterwhich the incidence of toxicity increases.

Also in this category is included Tra-madol , a weak agonist that combines itsweak opioid effect with potentiating activi-ty by reuptake inhibition of noeadrenalineand serotonin at the presynaptic level. Theadvantage of this medication may lie in theavailability in different presciption presen-tations as available in Europe (oral solution,capsules and slow release tablets) to betteradjust dosage regimen).

While these opioids are appropriate formild or intermittent pain, physician oftenrely excessively on these agents, frequentlycontinuing their use after they are no longereffective in an ill-advised attempt to avoidprescribing more potent opioids that arealso more highly regulated. The potency ofhydrocodone and dihydrocodone prepara-tions is greater than that of codeine andpropxyphene(86). These agents have per-ceived advantage of not requiring triplicateprescriptions (DEA Class C-III versus C-II inthe US), or special duplicated prescribingforms (as a restricted medication in Spain),although the clinician must be cautious notto exceed the usual recommended dose ofparacetamol (acetaminophen 4 Gm/day) asopioid requirements increase.

“Potent Opioids”:

When combinations of “weak” opioidsand adjuvants provide insufficient analgesiaor when pain is severe at presentation, morepotent opioids should be considered(19). Mor-phine, hydromorphone, transdermal fen-tanyl, and oxycodone are appropriate first-


line opioids for the treatment of moderate tosevere pain. Methadone, although inexpen-sive, and to a lesser extent levorphanol areusually reserved for special circumstancesbecause their half-lives are long and unpre-dictable, introducing the potential for accu-mulation, especially in the presence ofadvanced age and altered renal function(87).

Dosing Guidelines

Pharmacological therapy should be indi-vidualized in light of the specific characteris-tics and needs of each patient(88). The correctdose of an opioid is the one that effectivelyrelieves pain without inducing unacceptableside effects. Opioids should be initially beintroduced in low doses, since the earlydevelopment of side effects will impair com-pliance, but they should be rapidly titrated toneeded effect. If side effects ensue before ade-quate pain relief is established, they are treat-ed aggressively in an algorithmic fashion orother strategies should be applied(89, 90) whichare described later in this chapter.

a. Calculation of morphine equivalentdaily dose (MEDD): If the patient isalready on opioid medication, it isrecommended to calculate theMEDD in order to administer anequianalgesic dose of an alternateopioid if desired. Opioid dose con-version tables may helpful for calcu-lation, but should be followed cau-tiously allowing for interpatient vari-ability in opioid side effect sensitivity.

b. Basal and Rescue dosing guidelines:If analgesics are withheld until painbecomes more severe, sympatheticarousal occurs and then even potentanalgesics may be ineffective. Thus,a time-contingent schedule for theadministration of analgesics is gen-erally preferred to symptom-contin-gent administration. With prolongedadministration on demand, patternsof anticipation and memory of painbecome established and may con-tribute to suffering, even during peri-ods of adequate analgesia. Around-the-clock administration of appro-

priate analgesics maintains moreeven therapeutics blood levels anddecreases the likelihood of intolera-ble pain(91). Compliance and overallquality of analgesia are enhanced bythe regular administration of long-acting opioid analgesics for basalpain control, supplemented by ashort-acting opioid analgesicadministered as needed for break-through and incident pain. In prac-tice, controlled-release morphine,controlled-release oxycodone ortransdermal fentanyl are availablewhich cannot be broken, crushed orchewed. When these agents arepoorly tolerated, methadone or lev-orphanol may be prescribed, butcareful monitoring is required, par-ticularly in elderly patients.A drug of relatively high potency,short onset, and brief duration, suchas immediate-release morphine,hydromorphone, oxycodone, or oraltransmucosal fentanyl citrate isselected for as-needed administra-tion to manage exacerbation of pain(92). These agents should be pre-scribed every 2-4 hours as needed.When breakthrough medicationsare used more then 2-3 times over12 hours consistently, the dose ofbasal, long-acting analgesic may beincreased. If incident pain is a signif-icant problem, the patient should beinstructed to take the breakthroughdose in anticipation of pain-provok-ing activity. A new formulation oforal transmucosal fentanyl citratehas been shown to produce mean-ingful relief of breakthrough painwithin 5 minutes of initiating con-sumption, an onset that mimicsintravenous administration, despitethe noninvasive character of thistherapy (93) .

c. Agonist-antagonists and Partial Ago-nists:Agonist-antagonist (Nalbupine,Butorphanol) and partial agonist(buprenorphine) opioid though effec-


tive at the start of strong opioid therapyare generally avoided for a variety ofreasons, the most important of which isthe presence of a clinical ceiling anal-gesic effect, or dose above which toxi-city but not analgesia increases. How-ever, matrix transdermal presentationof buprenorpine available in Europemay make worthy the utilizationbuorenorphine in patches to enablegradual titration if intolerance tostronger opioids is severe.

Route of administration

1. Oral: When possible, analgesicsshould be administered orally or by a simi-larly noninvasive route (transdermal, rectal,transmucosal) to promote independenceand mobility and for ease of titration. In thepresence of a functional, intact GI system,once the dose is adjusted to account for thehepatic first-pass effect, oral administrationprovides analgesia that is as effective as par-enteral administration. The sublingual routeof adminstration was favored in the hospicesetting, but erratic absorption of morphineis problematic. Buccal administration offentanyl in the form of oral transmucosalfentanyl citrate has become a valuableoption for rapid analgesia in patients withsevere breakthrough pain(93).

2. Transdermal: When pain control isinadequate with oral analgesics or the oralroute is contraindicated, alternative meansof drug delivery route should be explored.Transdermal fentanyl provides steady plas-ma level of analgesic for 72 hours perapplied patch. The system’s rate-controllingmembrane regulates drug release at a slow-er rate than average skin flux, ensuring thatthe delivery system rather than the skin is themain determinant of absorption. Tempera-ture is the most important factor in the deter-minant of absorption, so patients should becautioned not to place a heating pad direct-ly over the patch. Although low level of fen-tanyl can be detected in the bloodstream justan hour after administration, a consistent,near-peak level is not obtained for 12-18hours after treatment is initiated.

3. Rectal: Rectal route is reliable forshort-term use except in the presence of diar-rhea, fistula, or other anatomical abnormal-ities. Morphine and hydromorphone areavailable in rectal preparations in the US,and oxymorphone rectal suppositories pro-vide 4-6 hours of potent analgesia(94). Rectalmethadone is also available in compound-ed form but should be used judiciously.

4. Other routes of administration: Con-tinuous subcutaneous or intravenous infu-sions of opioids by means of a pump, IV orsubcutaneous PCA, and intrathecal or epidur-al opioids administered via an externalizedcatheter or internalized pump can also beused (see interventional pain section below).

Side Effects

Constipation and miosis are the onlytwo opioid-mediated effects to which signi-ficant tolerance appears never to develop.Usually a combined mild laxative and sof-tener (Senokot-S) is prescribed when opioidtherapy is started. Patients should beinstructed about sliding-scale regimen untila regular bowel habit develops. An osmot-ic agent (e.g. Lactulose) is the usual second-line agent of choice for refractory constipa-tion. Severe constipation may leads to fecalimpaction that requires manual disim-paction or the sequential administrationglicerine suppositories and lavative enemasto avoid it.

Nausea and vomiting can be so strongthat it may require rehydration. Opioidinduced nausea and vomiting usuallyresolves spontaneously with continued opi-oid use ( tolerance to side effects), and thuspatients should be reassured and encour-aged to adhere to their prescribed regimenof analgesics. The properistaltic agent meto-cloprapramide is our first choice for opioidsrelated emesis, after ensuring constipationis not the cause. Metoclopramide is partic-ularly effective when gastric stasis is sug-gested by nausea, bloating and early satiety.Haloperidol, prochlorperazine, or chlor-promazine are other reasonable choices,especially when cost is in consideration(89).Ondansetron, a 5-HT3 anatagonist is com-


monly used as an adjunct to emeticchemotherapies, is sometimes useful, but isvery expensive. Dronabinol and corticos-teroids are other treatments for refractorynausea.

Opioid induced sedation that fails toimprove with time can often be managedeffectively with a psychostimulant such asmethylphenidate or dextroamphetamine(90).

When side effects are refractory toabove mentioned medications trials, opioidrotation should be considered, since sideeffects are often idiosyncratic and may notbe triggered by agents that are in otherrespects quite similar. If patients have per-sistent refractory side effects, more invasivemodalities should be considered.

Opioid addiction is always a fear inpatients receiving opioid medication,which is defined as a psycho-behavioralphenomenon with possible genetic influ-ence characterized by overwhelming druguse, nonmedical drug use, and continueduse despite the presence or threat of physi-ological or psychological harm. Physiciansshould be able to differentiate addictionfrom tolerance, which is defined as the needfor increasing dosages over time to maintaina desired effect, and physical dependence,a state characterized by the onset of char-acterized withdrawal symptoms when adrug is precipitously stopped or a specificantagonist is administered. Tolerance andphysical dependence are biophysical phe-nomenon that are inevitable and should beregarded as pharmacological effects.Patient and family education should clarifythese issues to aid in patient compliancewith the prescribed regimen. This educationis an essential element of a successful painrelief program.

Chronic administration of meperidine(also known as petidine) , leads to accumu-lation of normeperidine, a metabolite thatmay lead to frank seizure activities, espe-cially when renal function is impaired(95).Thus, meperidine has fallen from favor as auseful analgesic agent in the treatment ofcancer related pain.

3. Adjuvant analgesics

The aim of adjuvant therapy is to elicit anadditive or synergistic effect or to diminish thetoxicity of the primary therapy. In context ofcancer pain, either it enhances opioid-medi-ated analgesia, diminishes opioid-mediatedside effects or improves other symptoms asso-ciated with cancer(96). This analgesics are het-erogeneous group of medications originallydeveloped for purposes other then relief ofpain that have observed to promote analge-sia in specific clinical settings.

It is important fact to remember that (a)Not every agent belonging to each compo-nent drug class appears to posses analgesicproperties, (b) even agents with confirmedanalgesic properties relieve only specifictypes of pain derived from specific selectedconditions and (c) even then, pain relief doesnot accrue in all affected patients. A briefsummary of these drugs is presented here:

I. Sequential drug trials: The recognitionthat neuropathic pain often fails to respondadequately to the routine administration ofopioid and often responds in a binary fash-ion (no response or partial response) tomany adjuvants titrated over time, underliesthe contemporary concept of sequential tri-als. Candidates are best initiated singly inlow doses and titrated upward over time (2-4 weeks) until analgesia is achieved, sideeffects supervene, or the agent under trialcan be excluded and a new trial can becommenced(96) .

II. Antidepressants: The efficacy ofselected antidepressant as analgesics per se,independent of their effects on mood andnighttime sleep, has been demonstratedmostly in non-cancer models, although util-ity has been demonstrated for some agentsin cancer patients as well(97-104). The antide-pressant characteristically induce analgesiain responders with doses generally consid-ered insufficient to relieve depressionargues for a direct, independent underlyingmechanism of effect. In addition, althoughonset is not immediate, analgesia is gener-ally established more rapidly than are anti-depressant effects (typically 3-7 days versus


14-21 days). The operant mechanism forantidepressant-mediated analgesia presum-ably relates to increased circulating pools ofnorepinephrine and serotonin induced byreductions in the postsynaptic uptake ofthese neurotransmitters. It is also observedthat co-administration of at least Amitripty-line and Clomipramine increases plasmamorphine levels(103) .

Tricyclic antidepressants are used forpatients with neuropathic pain (e.g. pos-therpetic neuralgia, central pain, diabeticneuropathy), headache, arthritis, chroniclow-back pain, and psychogenic pain(96).The main indication is neuropathic painthat is relatively constant and unrelentingand that is not predominantly intermittent,lancinating, jabbing, or shocklike. Paroxys-mal neuropathic pain may also be treatedeffectively with tricyclic antidepressants butis often first treated with an anticonvulsant.

Amitriptyline and to a lesser extentimipramine remain the most extensivelystudied of these agents, and as a result theyare the usual first choices. Although rela-tively innocuous, side effects are especiallyprominent with these agents. Their metabo-lites include nortriptyline and desipraminewhich both have a better side effects profile.Some physician may prefer to start with nor-triptyline or desipramine as a first line ther-apy. Since newer the newer class of antide-pressants, the SSRIs (fluoxetine, paroxitine,sertraline, and others) are less effective fortreating pain then above-mentioned agents,they may have efficacy in treating depres-sion associated with pain.

Usually amitriptyline, nortriptyline, ordesipramine is started at 10-25 mg nightlyand gradually titrated upward, usually to arange of 50 to 125 mg and occasionallyhigher, until toxicity occurs or analgesia isestablished. Dry mouth, constipation,drowsiness, and dysphoria are the mostprominent of a wide range of side effects,which include urinary retention and cardiacdysrhythmia. Unlike the opioids, the devel-opment of tolerance is less robust, and sideeffects are less readily reversible. So if sideeffects are more prominent then analgesia,

the offending agent is usually discontinuedand a pharmacological analog or a drugfrom another class is started. The newerSSRI’s may be preferred over the hetero-cyclic agents for fragile elderly patient, or inpatients predisposed to developing anti-cholinergic side effects, patients whommultiple trials of tricyclics have failedbecause of side effects, and when depres-sion is a prominent co-morbidity.

III. Anticonvulsants: Carbamazepine,phenytoin, valproate, clonazepam, andmost recently gabapentin, alone or in com-bination with the tricyclic antidepressants,have been shown to successfully treat neu-ropathic pain(104). Most authorities considerthem as first choice for neuropathic pain andsecond-line therapy for relatively steady,constant neuropathic pain when tricyclicantidepressants are poorly tolerated, ineffec-tive, or only partially effective(96). Anticon-vulsants dampen ectopic foci of electricalactivity and spontaneous discharge frominjured nerves, in a manner analogous totheir salutary effects in seizure disorders.

Although carbamazepine therapy hasbeen most thoroughly studied anticonvul-sant for the treatment of neuropathic pain,it has largely been replaced by the newerand safer anticonvulsants includinggabapentin. Gabapentin is a newer anticon-vulsant and considered efficacious and welltolerated for neuropathic pain(105) . It shouldbe started by tolerance in doses at 300 to600 mg per day and subsequently increasedup to a maximun of 900 mg three or fourtimes a day until analgesia obtained or sideeffects developed. Occasionally, patientsrespond to much higher doses ofgabapentin without side effects. Felbamateis also known to interact with NMDA recep-tors, but its use is limited secondary to aplas-tic anemia. Other well tolerated newer anti-convulsants include topiramate, levitirac-etam, tiagabine, oxcarbazepine, lamotrig-ine, and zonisamide, but their use on thisindication has not been extensively studied.

IV. Baclofen: Baclofen is a g-aminobutyric acid (GABA) agonist, whichalthough generally used for spasticity, has


been reported to be effective for lancinat-ing, tic like neuropathic pain. It is usuallystarted at 5 mg twice or three times day orand may be titrated up to 30-90 mg/day, astolerated. It is also useful for spasticity; espe-cially due to spinal cord injury and multiplesclerosis in the intrathecal route(106).

V. Oral local anesthetics: Oral mexile-tine is drug from the class III anthiarrytmicsused initially as a disproved diagnosticintervention in neuropathic pain, and lateras an adyuvant, usually regarded as a third-line association agent for continuous orintermittent neuropathic pain disorders.Acting as a non-selective Na+ channelblocker , several studies have shown disap-pointing efficacy and an important rate ofside effects when use in dosis greater than300 mg a day. No other oral local anesthet-ic is currently recommended

VI. Amphetamines: The most widelyaccepted use for amphetamines in the treat-ment of cancer pain is as a means to reverseopioids induced sedation(107). Research sug-gests that dextroamphetamine andmethylphenidate possess some analgesicproperties and are excellent antidepres-sants(108). The amphetamines are well toler-ated by cancer patients and instead of induc-ing anorexia, these agents typically have aparadoxical effect of increasing appetite byenhancing alertness. Nervousness and agi-tation are the most common side effects.

VII. Corticosteroids: Corticosteroids areknown for its efficacy for treatment of acutepain resulting from raised intracranial pres-sure and spinal cord compression second-ary to its effect in reducing peritumoral ede-ma and inflammation with consequentrelief of pressure and traction on nerves andother pain-sensitive structures. Improve-ments in symptoms are often rapid and dra-matic but usually depend on continuedadministration. This effects are short-livedand usually level off in few weeks.

Dexamethasone is the usual drug ofchoice because it has less potent mineralo-corticoid effects. Side effects ranged fromdysphoria and diabetes mellitus to floridpsychosis. For oncologic emergencies, 100

mg of dexamethasone should be adminis-tered as bolus dose, followed by intra-venous maintenance dose. The large bolusdose produces severe but transient perinealburning via unknown mechanism. For non-emergencies, dose is 2-6 mg three or fourtimes a day.

VIII. N-Methyl-D-Aspartate Antago-nists: The NMDA receptor has been welldescribed and implicated in the transmis-sion of pain. Ketamine and dextromethor-phan, partial NMDA antagonists, appear tomediate pain by this mechanism. Subanes-thetic doses of ketamine have been admin-istered for prolonged periods with fair suc-cess in a small number of patients withrefractory neuropathic cancer pain(109,110).Because of side effects, ketamine infusionshould be reserved as a late treatment forhighly refractory neuropathic pain.

IX. Alpha-2 Adrenergic antagonists:The centrally acting antihypertensive cloni-dine has been observed to promote analge-sia for neuropathic pain when administerednear the neuraxis. Epidural administrationhas received U.S. Food and Drug Adminis-tration (FDA) approval. In a prospectiverandomized study of 38 patients withsevere cancer pain(111) that persisted despitelarge doses of spinal opioids, the additionof epidural clonidine was associated withsignificant improvement in 45% of patientsoverall and 56% of patients with neuro-pathic pain. Hypotension during the initia-tion and rebound hypertension duringwithdrawal are the main potential risk oftreatment.

X. Other adyuvants: Strontium is ananalogue of calcium and is taken up by theskeleton into active sites of bone remodel-ing and metastasis. A large clinical trialdemonstrated that a 10 micro curie IV dosewas an effective adjuvant to local radiother-apy, and that it reduced disease progression,decreased new sites of pain, and decreasedsystemic analgesics use(112 ). It is also a use-ful adjuvant for diffuse metastatic bonepain. The latency of response can be as longas 2-3 weeks, in which case patients mustbe instructed to continue analgesic therapy.


The biphosphonate pamidronate disodi-um, inhibits osteoclastic bone resorptionand has been shown to reduce pain andskeletal complications, such as pathologicalfracture in breast cancer patients and multi-ple myeloma(113,114 ). The drug is adminis-tered in a 90 mg intravenous infusion in 2 hrapproximately every 4 weeks. Excellentreviews of the literature on this topic are eas-ily available and recommended to read(115).

Interventional Pain Management

When a comprehensive trial of pharma-cological therapy fails to provide adequateanalgesia or leads to unacceptable sideeffects, consideration should be given toalternative modalities.

1. Continuous subcutaneous infusionof opioids (CSCI): It is an excellent optionfor patients whose medical condition pre-cludes the use of the oral route or whosepain is poorly controlled despite large dos-es of oral opioids(116, 117).

Starting doses are calculated based onthe 24-hour dose requirement of intra-venous morphine with a conversion tableand divide it by 24, which gives the hourlyrate. Tissue irritation is minimized when vo-lumes under 1 to 2 ml/hour are prescribed(by concentrating the mixture). A 27-gaugebutterfly needle is inserted subcutaneouslyanywhere with the most preferred sitesincluding the infraclavicular fossa or chestwall for the ease of ambulation.

Absorption of subcutaneously adminis-tered opioids is rapid, and steady-state plas-ma levels are generally approached withinan hour(117). Most parenteral opioids are suit-able for CSCI, although morphine andhydromorphone are used most commonlyand meperidine, methadone and penta-zocine should be avoided because of thepotential for tissue irritation. Rescue dosesshould be given as subcutaneous injectionequal to the hourly dose to be administeredevery 1-2 hour as need.

2. Continuous intravenous infusion ofopioids (CII): This modality is indicated in a

group of patients include intolerance of theoral route because of GI obstruction, mal-absorption, opioid induced vomiting, dys-phagia, or the requirement of large numberof pills. It is also indicated in a patient get-ting prominent bolus effect with intermittentinjection, the necessity for rapid titrationand requirement of bolus injections thatexceed nursing capabilities. It is very simi-lar to CSCI, although CSCI is preferred in thehome care setting unless a permanent vas-cular access device is already in place(117) .

Patient controlled analgesia (PCA) is asimilar version and excellent option but isreserved for patients with the capacity tounderstand and use this modification cor-rectly. Dose should be adjusted upwarduntil pain relief is adequate or side effectsbecome intolerable.

3. Intraspinal Analgesia: Neuraxialanalgesia is achieved by the epidural orintrathecal administration of an opioidsalone or in combination with other agents.With the use of neuraxial analgesia, painrelief is obtained in a highly selective fash-ion with an absence of motor, sensory, andsympathetic effects, making these modali-ties highly adaptable to the home care envi-ronment(118-122). The principle of neuraxialopioid therapy is that introducing minutequantities of opioids in close proximity totheir receptors (substantia gelatinosa of thespinal cord) achieves high local concentra-tions(119). With this therapy, analgesia maybe superior to that achieved when opioidsare administered by other routes, and sincethe absolute amount of drug administered isreduced, side effects are minimized.

The neuraxis can be accessed via anintrathecal, epidural, or intraventricularapproach, although the intraventricularroute is used infrequently, primarily forintractable head and neck pain, and thenusually when an access device (Ommayareservoir) is already in place(123). The mostimportant aspect of this therapy is itsreversibility and the reliability and simplic-ity of advance screening measures to con-firm efficacy. Screening can generally beaccomplished on an outpatient basis by


observing the patient’s response either to amorphine infusion via a temporary percuta-neous epidural catheter or a single-shotintrathecal injection. If improved pain con-trol and reduced side effects are sufficient-ly profound to warrant more prolongedtherapy either with temporary catheter forperiod of days to weeks or replacement witha permanent implanted catheter along withimplanted medication deliverable pump. Chronic administration of epidural opioidscan be accomplished by intermittent bolusadministered by the patient, family mem-bers, nursing personnel, or more common-ly by continuous infusion via a standardPCA portable infusion pump connected tothe epidural port. Continuous infusion is apreferred means of administration becauseintervals of pain between injections areavoided. More commonly a combination ofepidural opioids and dilute local anesthet-ics agents have been determined to be safeand are often beneficial for pain that isrefractory to opioids alone(124).

Subarachnoid catheter placement is analternative to epidural administration. Opi-oids requirements are less than with epidur-al administration because of more directaccess to the spinal cord. Many factors areconsidered in the decision for an externalpump system versus an implantable pump.These include factors that lead us to anexternal system: a short life expectancy (< 3months), the need for frequent patient con-trolled doses (such as with severe incidentpain), the need for an epidural infusion(which generally requires infusion volumestoo great for the implanted pump), the lackof reprogramming/refilling capabilities nearthe patient’s home, or payor constraints. Weuse a variety of catheters for our externalsystems including a tunneled Arrow Flex-Tip catheter, the Du Pen’s epidural catheter,and the Sims epidural portacath.

Factors that lead us to consider animplantable intrathecal pump include: alonger life expectancy (> 3 months), accessto pump refill/reprogramming capabilities,diffuse pain (e.g.- widespread metastasis),and favorable response to an intrathecal tri-

al. We use a programmable (Synchromed,Medtronic, Inc., Minneapolis MN) pump forpermanent implantation.

A recently published multicenterprospective randomized clinical trial bySmith, et al., compared intrathecal therapyto continued medical management reveal-ing a slight trend toward better analgesia inthe intrathecal group (not statistically signif-icant), but improved side effect profile andincreased survival in the intrathecalgroup(125). Our group reported a significantimprovement in pain scores (NRS 7.9 to 4.1)and decrease from 588 mg/day oral mor-phine equivalents to 294 mg/day followingintrathecal analgesia(126).

Neuraxial medication is expensive, par-ticularly as to whether an implanted pumpis a justifiable expense in a patient with alimited life expectancy. Two studies evalu-ated the external versus internal pump, withthe ongoing costs of external pump leaseand tubing versus the high initial cost of theimplanted pump. These analysis show a“break even” point at approximately 3months(127, 128).

Recently Hassenbusch and colleaguespublished current practice data on intrathecalmedication management. A survey of 413physicians managing 13,342 pts was per-formed. It showed a variety of medicationsbeing used in the intrathecal pump including:morphine (48%), morphine/bupivacaine(12%), hydromorphone (8%), morphine/cloni-dine (8%), hydromorphone/clonidine (8%),morphine/clonidine/bupivacaine (5%), mor-phine/baclofen (3%), and others (< 3%). Oth-er drugs mentioned included: fentanyl, sufen-tanil, ziconotide, meperidine, methadone,ropivacaine, tetracaine, ketamine, midazo-lam, neostigmine, droperidol, and nalox-one(129).

Side effects in forms of nausea, respira-tory depression, pruritus, urinary retention,dysphoria are common for opioid-naïvepatients, but are extremely rare in opioid-tolerant individuals(118).

4. Neural Blockade Techniques: a. Local anesthetic nerve blocks: Local

anesthetic injections can be broadly


classified as being applicable fordiagnostic, and/or therapeutic pur-poses(130-139).a1. Diagnostic Blocks: Diagnostic

blocks help to characterize theunderlying mechanism of pain(nociceptive, neuropathic, sym-pathetically mediated) and todiscern the anatomical path-ways involved in pain transmis-sion. Its main indication is as apreliminary intervention con-ducted prior to a therapeuticnerve block or other definitivetherapy. This helps the clinicianto determine the potential forsubsequent neurolysis if indi-cated. While results often havegood predictive value, they arenot entirely reliable.

a2. Therapeutic blocks: The role ofthis block in cancer patients islimited typically because oftransient nature of attendantpain relief. Therapeutic injec-tions of local anesthetics, withor without corticosteroid, intotrigger points, subcutaneousfoci of localized muscle spasm,may provide lasting relief ofmyofascial pain(134). This bed-side procedure is particularlyuseful when muscle spasm ariseas a result of prolonged bed restand for pain that follows thora-cotomy, mastectomy, or radicalneck dissection. Diffuse subcu-taneous injection of coricos-teroids and local anestheticsmay be useful in acute herpeszoster or post-herpetic neural-gia. Epidural steroid-local anes-thetics injection are unlikely toprovide lasting relief for backpain due to progressive neo-plastic lesions. Local anestheticinjections administered in aseries may contribute to lastingpain relief in the setting of post-traumatic sympathetically

maintained pain (e.g. reflexsympathetic dystrophy or com-plex regional pain syn-drome)(135-137). Although infre-quent, such symptoms mayarise as a result of tumor inva-sion of nervous system structure(e.g. brachial or lumbosacralplexopathy), in which caseeither local anesthetic blockadeof the stellate ganglion or lum-bar sympathetic chain has beenused with some success torelieve pain.

b. Neurolytic nerve blocks: Neurolyticblocks have played an important rolein the management of intractablecancer pain. This modality should beoffered when pain persists despitethorough trials of aggressive pharma-cological management or when drugtherapy produces unwanted anduncontrollable side effects. Patientselection is important, including: (a)severe pain, (b) pain is expected topersist, (c) pain cannot be modifiedby less invasive means, (d) pain iswell-localized, (e) pain is well-char-acterized, (f) pain is not multi-focal,(g) Pain is of somatic or visceral ori-gin, (h) patient with limited lifeexpectancy.

Alcohol and Phenol are the only agentscommonly used to produce chemical neu-rolysis. Ethyl alcohol is a pungent, colorlesssolution that can be readily injected throughsmall-bore needles and that is hypobaricwith respect to CSF. For peripheral and sub-arachnoid blocks, alcohol is generally usedundiluted (referred to as 100% alcohol,dehydrated alcohol, or absolute alcohol),while a 50% solution is used for celiacplexus block. It should not be exposed toatmosphere, because absorbed moisturedilutes it. Alcohol injection is typically fol-lowed by intense burning pain and occa-sionally erythema along the targeted nervedistribution. Denervation and pain reliefsometimes accrue over a few days follow-ing injection.


Phenol is fairly unstable at room tem-perature. It lasts at least one year whenrefrigerated and kept away from light. Phe-nol can be used in 3-15 % concentrationand with saline, water, and glycerol or radi-ological dye. It is relatively insoluble inwater, and as a result concentration inexcess of 6.7 % cannot be obtained at roomtemperature without adding glycerine toincrease its solubility in water. Phenol withglycerine is hyperbaric (versus alcoholbeing hypobaric) in CSF, but is so viscid thateven when warmed, it is difficult to injectthrough needles smaller then 20 gauge.Phenol has a biphasic action-its initial localanesthetic action produces subjectivewarmth and numbness that usually giveway to chronic denervation over a day’stime. Hypoalgesia after phenol typically isnot as dense as after alcohol, and qualityand extent of analgesia may fade slightlywithin the first 24 hours of administration.

Subarachnoid (intrathecal) injections ofalcohol or phenol continue to play animportant role in the management ofintractable cancer pain in carefully selectedpatients. Neurolytic neuraxial block pro-duces pain relief by chemical rhizotomy.Since alcohol and phenol destroy nervoustissue indiscriminately careful attention tothe selection of the injection site, volumeand concentration of injectate, and selec-tion and positioning of the patient are essen-tial to avoid neurological complications(139-

141). Most authorities agree that neither alco-hol nor phenol offers a clear advantageexcept insofar as variations in baric proper-ties facilitate positioning of thepatient(142,143). Except for perineal pain, alco-hol is usually preferred, since most patientsare unable to lie on their painful side, as isrequired for intrathecal phenol neurolysis.In one of the analysis of 13 published seriesdocumenting treatment with intrathecal rhi-zolysis of more than 2500 patients Swerd-low reported that 58% of patients obtained“good” relief; “fair” relief was observed inan additional 21%, and in 20% of patients“little or no relief” was noted(142). Averageduration of relief is estimated at 3 to 6

months, with a wide range of distribution.Reports of analgesia persisting 1 to 2 yearsare fairly common(144). In representativeseries using alcohol (n= 252) and phenol (n= 151), a total of 407 and 313 blocks wereperformed respectively (145,146). In these twoseries, neither motor weakness nor fecalincontinence occurred, and of 8 patientswith transient urinary dysfunction, inconti-nence persisted in just 1.

Subarachnoid neurolysis can be per-formed at any level up to the mid-cervicalregion, above which the risk of drug spreadto medullary centers and the potential forcardiorespiratory collapse increases(147).Blocks in the region of the brachial outfloware best reserved for patients with preexist-ing compromise of upper limb function.Similarly, lumbar injections are avoided inambulatory patients, as are sacral injectionsin patients with normal bowel and bladderfunction. Hyperbaric phenol saddle block isrelatively simple and is particularly suitablefor many patients with colostomy and uri-nary diversion. Until recently, epidural neu-rolysis was performed infrequently. Resultswere inferior to those obtained with sub-arachnoid blockade, presumably becausethe dura acts as a barrier to diffusion, result-ing in limited contact between the drug andtargeted nerves(144, 148).

Sympathetic blockade also producesprolonged relief of pain in cases where thepain is sympathetically mediated(135,136) .When local anesthetic sympathetic blocksprovide only temporary relief or when clin-ical findings suggest visceral or sympathet-ically mediated pain, consideration ofchemical sympathectomy is warranted.

Celiac plexus block continues to be oneof the most efficacious and common nerveblocks employed in patients with cancerpain(130). It has great potential for relievingupper abdominal and referred back painsecondary to malignant neoplasm involvingstructures derived from the foregut (distalesophagus to mid-transverse colon, liver,biliary tree, and adrenal glands). The mostcommon indication for celiac axis block ispancreatic cancer. Celiac axis block is most


commonly performed by positioning nee-dles bilaterally either antero- or retrocrural-ly via a posterior percutaneous approach

The retrocrural technique is more accu-rately called a splachnic nerve block.Despite the proximity of major organs (aorta,vena cava, kidneys, pleura) and the require-ments for a large volume of neurolytic (30-50 ml of 50% alcohol in the anterocruraltechnique, much less volume in the retro-crural) complication rates are uniformly low,although some complications are serious(149-

151). In contemporary practice most authori-ties consider radiological guidance manda-tory to verify needle placement(151). Tradition-ally fluoroscopy has been used, but CT guid-ance is increasing in popularity becausevascular structures, viscera, and masses canbe visualized(152). Although studies have beencriticized for methodological deficiencies,85 to 94% incidence of good to excellentrelief of pain has been obtained in large seriesof patients undergoing one or more neurolyt-ic celiac plexus blocks for pain from pancre-atic cancer, or a variety of intraabdominalneoplasms(153). In one of the randomizeddouble-blind, placebo-controlled study ofintraoperative celiac neurolysis demonstrat-ed that treated patients had not onlyimproved pain control, reduction in opioiduse and improved function but also statisti-cally significant improvement in survival(7) .This issue has very recently been submittedagain through a well designed methanalysisby the Mayo Clinic group, and has reaffirmedthe efficacy in decreasing pain rating withinthe several weeks after the block, anddecreasing the opioid requirements then on. Unfortunately they have not found signifi-cant effects in the quality of life indexes whencompared to standard pharmachologicaltreatment(50). Our group at MD AndersonCancer Center has reported in abstract forma retrospective study revealing an 83%reduction in pain score and 73% reductionin MEDD after splachnic nerve block(154).

Stellate ganglion block, with repeatedlocal anesthetic of the sympathetic outflowto the head, neck, and arm often providepersistent relief of sympathetically main-

tained pain affecting these regions. Stellateganglion neurolysis is hazardous because ofthe close proximity of other important struc-tures (brachial plexus, laryngeal nerves,epidural and subarachnoid space, vertebralartery) and the potential for injury becauseof inaccurate needle placement. If localanesthetic injections have been document-ed to provide temporary relief of pain, sur-gical extirpation of the ganglia may be con-sidered, or neurolysis may be performedcautiously using radiological guidance andsmall volumes of injectate(155).

Neurolytic lumbar sympathetic block ismost applicable for pain in the lowerextremities due to lymphedema or reflexsympathetic imbalance, although it has alsobeen applied for rectal and pelvic pain inanecdotal fashion(131).

Superior hypogastric plexus block(156) isgenerally preferred for intractable chronicpelvic or rectal pain of neoplastic origin. Incontrast to subarachnoid injection, risks ofbowel, bladder, and motor dysfunction witheither lumbar sympathetic or hypogastricblock, even when performed bilaterally, areextremely low, particularly with radiologi-cal guidance.

In the first published study of superiorhypogastric block(156), 28 patients withintrapelvic neoplasms or radiation enteritiswere studied, and all had significant orcomplete relief of pain with no complica-tions. In all but 2 patients with pain due toneoplasm, relief persisted until death (3 to12 months). In another study of 26 cancerpatients with severe (10 out of 10 intensity)intractable pelvic pain: 70% had satisfacto-ry relief (less than 4 out of 10 intensity) andthe remaining patients, moderate relief (4to7 of 10)(157). Complications were notobserved, and no patients with satisfactoryrelief required repetition out to a 6 monthfollow up.

The ganglion impar is a solitaryretroperitoneal structure at the level of thesacrococcygeal junction that marks the ter-mination of the paired paravertebral sympa-thetic chains. Although the anatomical inter-connections of the ganglion impar are rarely


described in any detail, even in the anatomyliterature, the sympathetic component ofperineal pain syndromes appears to deriveat least in part from this structure. The firstreport of interruption of the ganglion imparfor the relief of anal, genital, or perineal can-cer related pain appeared in 1990(158). Of 16patients, 8 had complete, durable relief ofpain, and the remainder had significantreductions in pain. Blocks were repeated intwo patients with further improvement. Nocomplications occurred, and follow-up,which depended on survival, was carriedout for 14 to 120 days. The technique entailsthe use of a 20- or 22-gauge spinal needlethat is manually bent near its hub at about30?. The needle is introduced through theanococcygeal ligament with its concavityoriented toward the concavity of the sacrumand coccyx. Under fluoroscopic guidancethe needle is advanced until its tip lies nearthe anterior surface of the junction of thesacrum and coccyx, posterior to the rectumwhere injection takes place.

More recently, Radiofrequency-generat-ed thermal lesions are another effective meansof inducing therapeutic nerve injury and whendirected to the tumor itself, it can have a tumo-ricidal effect often with salutary effects onsymptoms(159) . An optimal result requires thejudicious use of fluoroscopy for placement ofneedle and application of simple but essentialadjuncts including the use of a nerve stimula-tor to avoid the motor root if applicable.

Peripheral/Cranial Nerve Blocks:Peripheral nerve blockade has a limited rolein the management of cancer pain(139). Neo-plastic head and neck pain is many timesdifficult to control because of rich sensoryinnervations of the structures. In selectedpatients, blockade of involved cranialand/or upper cervical nerves is very helpful.Blockade of trigeminal nerve within theforamen ovale at the base of skull or itsbranches may be beneficial for facialpain(160). If neural blockade is not effective,intraspinal opioid therapy by means of animplanted cervical epidural catheter orintraventricular opioid therapy may be con-sidered(161,162).

5. VertebroplastyMany cancer patients with metastatic

vertebral or osteoporotic compression frac-tures(VCFs) present with movement-relatedback pain. Percutaneous vertebroplasty(PV) is a minimally invasive procedureinvolving injecting an opacified bonecement (usually polymethymethacrylate orPMMA) into the fractured vertebral body toalleviate the pain and perhaps enhancestructural. This procedure is performed byplacing needles under fluoroscopic guid-ance with a uni- or bipedicular approach.PMMA is injected in a carefully controlledmanner to avoid unintended cement spreadinto the spinal canal. Injection is stopped assoon as cement start approaching in poste-rior on third of vertebral body. PV has beenshown efficacious in treating VCF relatedpain in cancer patients(163).

6. Neuromodulation:Spinal cord stimulation is widely popu-

larized for refractory neuropathic chronicpain states. It has limited applicability incancer pain states, except in ongoing chron-ic neuropathic pain states. Selection of thispatient population is very important in can-cer group, as MRI is contraindicated afterthis devise is placed.

Neurosurgical palliative techniqueshave fallen into less favor as more medica-tions and reversible, titratable, lower risktechniques have largely replaced these pro-cedures. Pituitary ablation entails destruc-tion of the gland by means of the injectionof a small quantity of alcohol through a nee-dle positioned transnasally under light gen-eral anesthesia. This technique is effectivein relieving pain originating from dissemi-nated bony metastases, particularly second-ary to hormone-dependent tumors (breastand prostate)(164). Commissural myelotomyhas been reported to be efficacious in can-cer pain refractory to more conservativetherapy(165). Percutaneous cordotomy pro-duces a thermal lesion within the substanceof the spinal cord and reliably relieves uni-lateral truncal and lower limb pain (166). Aswith pituitary ablation, it necessitates a highdegree of skill and expertise, but pain relief


is often profound and the rigors of a majorneurosurgical procedure are avoided.

Behavioral Pain Management

Different behavioral pain managementtechniques have been used in patients withcancer includes hypnosis, relaxation,biofeedback, sensory alteration, guidedimagery, and cognitive strategies (167) . Relax-ation and imagery training significantlyreduce visual analog scale scores in patientswho have Mucositis during bone marrowtransplant(168). This training is probably mosteffective for patients who have no significantpsychological or psychiatric problems(169) andin insightful psychology-minded patients.

Home-based and hospice care

For years together, hospice was oftenincorrectly regarded as a place people go todie, but correctly it is a philosophy of carethat is “a blend of clinical pharmacologyand applied compassionate psycholo-gy”(170,171). In the United States hospice carehas developed primarily as a home basedservice, with a minority of institutions offer-ing short inpatient stays to stabilize refrac-tory symptoms and to provide respite foroverwhelmed families. In Spain, a very wellorganized Spanish Palliative Care Society(SECPAL) has promoted intensively the cre-ation of palliative care units (hospital, selfstanding and ambulatory-hospital basedunits) up to nearly 310 groups distributedacross most of the country’s geography withgreat success.

The principles of home-based pain man-agement are in most respects similar to thosethat apply to ambulatory and inpatient painmanagement. Differences generally relate toa recognition that further curative therapy isfutile rather than that care is being providedat home. No compromise in quality of carebased on where it is delivered is justified.

Hospice care is comfort oriented, focus-ing specifically on alleviating symptomsrather than necessarily treating their underly-

ing cause or causes. Factors that influencethe selection of home treatment areadvanced, incurable disease, realization andacceptance of the appropriateness of pallia-tive care (care directed at preserving comfortand the quality of life rather than at curing thetumor and extending life), and a desire to diein familiar surroundings. Many difficultiesassociated with providing intensive palliativecare at home can be reconciled by educationand orientation of the family and that can beperformed with coordination with healthcare institutions, home care nursing, labora-tory, and pharmacy services.

CONCLUSIONS

Palliative Care and Pain managementare closely bounded to everyday practice.A basic knowledge update about the currentstatus of concepts and techniques for Can-cer pain management is of prime impor-tance for every pactioner caring for Cancerpatients as a resource for appropiate infor-mation and solution to pain problems of hispatients. As presented, Acute and chronicpain occurs in a high frequency of cancerpatients. Inadequate assessment and treat-ment of pain and other distressing symp-toms may interfere with primary antitumortherapy and markedly detract from theirquality of life . While a strong focus on paincontrol is important independent of diseasestage, it is a special priority in patients withadvanced disease who are no longer candi-dates for potentially curative therapy.

While rarely eliminated altogether, paincan be controlled in the vast majority ofpatients, usually with the careful applica-tion of straightforward pharmacologicalmeasures combined with diagnostic acu-men and conscientious follow up. In thesmall but significant proportion of patientswhose pain is not readily controlled withnoninvasive analgesics, a variety of alterna-tive measures, when selected carefully, arealso associated with a high degree of suc-cess provided by specialized in pain clinics.An increasingly large number of anesthesi-ologists, oncologists, and psychologists and


other medical and non-medical professionshave come to recognize that far from anexercise in futility, caring for patients withadvanced irreversible illness can be a high-ly satisfying endeavor that is usually metwith considerable success. Thus, no patientshould ever wish for death or think ineuthanasia as a result of inadequate controlof pain or other symptoms, and cliniciansmust never communicate overtly or indi-rectly that nothing more can be done. Com-prehensive cancer care is best regarded asa continuum that commences with preven-tion and early detection, focuses intenselyon curative therapy, and ideally is renderedcomplete by a seamless transition to pallia-tion and attention of quality of life.

The future of cancer pain relief is bright,as much mechanistic research is looking intodifferent groups of specifically targeted med-ications including tumor necrosis alpha recep-tor antagonists, inhibitors of glutamate release,substance P inhibitors, nitric oxide synthetaseinhibitors, and other novel compounds.

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WHAT EVERY PROFESSIONAL WORKING IN PALLIATIVE CARE … · 2013. 1. 13. · age, or described in terms of such damage”(2) relates better to Palliative Care, on which dai-ly practice