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The American Journal of Surgery 188 (Suppl to July 2004) 31S–35S

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Practical treatment of pain in patients with chronic wounds:pathogenesis-guided management

Gordon Freedman, M.D.a,*, Hyacinth Entero, B.A.b, Harold Brem, M.D.b

aDepartment of Anesthesiology, Mount Sinai Pain Management Service, 5 East 98th Street, Box 1192, Mount Sinai School of Medicine,New York, New York 10029-6574, USA

bDepartment of Surgery, Columbia University College of Physicians & Surgeons, New York, New York, USA

bstract

In addition to its own inherent morbidity, the pain associated with chronic wounds presents a primary obstacle to healing. To initiate safend effective therapy, we used a multidisciplinary approach that required the wound-healing clinician and pain-management practitioner toork together to diagnose and treat the pain associated with these wounds. This approach emphasizes wound pathophysiology, which

acilitates treatment modalities that focus on the cause of the pain as well as more efficient analgesia. All wound patients were approachedith the assurance that they should not experience pain. The most important part of pain control is objective assessment and assuring patients

hat their pain will be resolved. Differential diagnosis is critical (eg, wound pain associated with infection, necrosis, spinal cord injury,europathy). We determined that to resolve pain, the following 4 goals must be achieved: (1) removal of all nonviable, locally infected tissuend elimination of all cellulitis; (2) determination of wound pathogenesis; (3) availability of both local and systemic analgesia; and4) assessment of objective improvement through the periodic use of an analgesic scale. By following this protocol, the wound-healinglinician can expect decreased length of hospital stay and resolution of pain in nearly all patients with wounds. © 2004 Excerpta Medica,nc. All rights reserved.

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ur integrated team approach to treatment of wound painnvolves specialists from both the wound-healing and pain-anagement teams. This approach allows for a comprehen-

ive evaluation and strategy in managing the patient’s pain-ul wound. Based on this approach, guidelines derived fromhe 10 most common causes of chronic wounds were estab-ished for treating pain [1] (Table 1). Ischemia, tissue dam-ge, and neuropathy represent the 3 broad etiologies of theain in patients with chronic wounds. For each of thesetiologies, we constructed a general pain management pro-osal based on correcting pathologic causes of the chronicound. Case histories, representative of our experience in

housands of cases of wound and pain management, illus-rate our basic pain treatment strategies for chronic woundsesulting from ischemia, tissue damage, and neuropathy.

* Corresponding author. Tel.: �1-212-241-6372; fax: �1-212-348-695.

E-mail address: gordon.freedman@mountsinai.orgThis work was supported in part by the United Spinal Association and

ty Grant No. DK059424 from the National Institutes of Health.

002-9610/04/$ – see front matter © 2004 Excerpta Medica, Inc. All rights reseroi:10.1016/S0002-9610(03)00289-7

ur multidisciplinary approach alleviated pain for almostll the patients treated by our team.

schemic wound pain management

ase history

An 86-year-old woman with a 20-year history of arterialnsufficiency experienced sharp pain in the posterior aspectf her left lower extremity, associated with blanching ery-hematous lesions over her toes. The pain worsened withalking and subsided with rest. She had a left lower-ex-

remity revascularization procedure 10 years before the cur-ent presentation. She was under the care of the vascularurgeon on the wound team, who assessed that she was notcandidate for angioplasty or further bypass. The patient

ated her pain as 10/10, on a scale where 10 was the worstain she could imagine. The pain disrupted her sleep, andhe took ibuprofen to no avail.

The patient was started on tramadol, and 10-mg nortrip-

yline was prescribed at bedtime for sleep and analgesia. A

ved.

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eries of left lumbar sympathetic nerve blocks was per-ormed to provide analgesia and increased blood flow to theower extremity.

ase discussion

Ischemic wounds are mainly caused by arterial insuffi-iency secondary to vaso-occlusive disease (eg, arterioscle-osis) or vasospastic disease (eg, Raynaud phenomenon).ain management of these wounds focuses on treating thenderlying ischemia to relieve the pain.

Sympathetic nerve blocks are relatively noninvasive mo-alities for increasing regional blood flow to an area ofschemia. Sympathetic nerve inhibition produces smoothuscle dilation of the arterioles and venules, decreases

eripheral resistance, increases capillary flow, and, second-rily, increases skin capillary oxygen tension and saturation.his effect of a “nonoperative microvascular bypass” pro-ides a collateral blood flow to areas not amenable tourgical bypass procedures. Sympathetic blockade can beerformed at several anatomical levels. Epidural anesthesiay way of percutaneous catheters, with diluted concentra-ions of local anesthesia, provides differential sympatheticlockade while maintaining motor function. Tunneling ofhe catheter allows long-term usage or home use.

A more regional sympathetic block would theoreticallyecrease the chance of the “steal phenomenon,” whichhunts blood away from ischemic areas. A lumbar sympa-hetic percutaneous block, on an ambulatory basis underocal anesthesia with fluoroscopic guidance, is used fre-uently for lower-extremity ischemia. This block reducesotor dysfunction, hypotension, and vascular “steal.” For

onger-lasting results, neurolytic agents [2] or radiofre-uency lesioning can be performed.

Spinal cord stimulation also blocks sympathetic output athe spinal cord level and is used in those cases refractory toess invasive techniques [3]. The procedure increases re-ional blood flow, promotes local wound healing, and isccomplished by placing electrodes in the epidural spaceosterior to the dorsal columns of the spinal cord. Thus, usef sympathetic blocks, by whatever means, increases lower-

able 1auses of pain in the 10 most common chronic wound etiology

hronic Wound Etiology Cause

rterial insufficiency Ischemiaickle cell disease Ischemiaenous stasis disease Tissue damage

nfection Tissue damageressure Tissue damagebesity Tissue damageteroids Tissue damagehemotherapy Tissue damageadiation Tissue damageiabetes mellitus Neuropathy/ischemia

xtremity blood flow and decreases pain. Analgesia is ob- u

ained by correcting the underlying physiologic causes ofschemic pain.

Oral analgesics (eg, nortriptyline and tramadol) alsoere used in our case study to supplement the primary

njection treatment. Nortriptyline is a tricyclic antidepres-ant with sleep-promoting properties and has analgesic ef-ects that arise from actions on the descending inhibitorypinal cord pain pathways. Nortriptyline exhibits fewer an-icholinergic side effects than other tricyclics, such as am-triptyline, and is therefore better tolerated (especially bylderly patients). Tramadol provides analgesia by weaklyinding to opiate receptors, as well as analgesic effectsimilar to tricyclic antidepressants, at the spinal cord level.t has fewer side effects than either the opioids or tricyclicsnd, consequently, is efficacious as an as-needed analgesic,specially for elderly patients.

issue damage wound pain management

ase history

The following history is representative of any nonpara-yzed patient with a venous ulcer or pressure ulcer:

A 33-year-old, 325-lb man with non–insulin-dependentiabetes mellitus (NIDDM) and a 5-year history of venouseflux and ulcer in his right lower extremity had a large,ainful, irregular ulcer located superior to the medial mal-eolus. It was surrounded by hyperpigmented skin withlassic dermatitis. The patient described sharp, burning,tching pain that was constant and further exacerbated atight. He was taking a cyclooxygenase-2 (COX-2) inhibitora nonsteroidal anti-inflammatory drug [NSAID]) and acet-minophen with codeine for the pain, which provided mildelief with some associated nausea.

This patient was then started on an extended-releasepioid (fentanyl patch), an anticonvulsant (gabapentin), aricyclic antidepressant (amitriptyline), and as-needed tram-dol for the pain. He continued taking the COX-2 inhibitor.

ase discussion

This patient had venous reflux and a painful leg ulcer.enous ulcers are usually secondary to reflux between theeep and superficial lower-extremity venous systems. Theeflux leads to increased venous pressure, venous dilation,ncreased capillary permeability, and extravasation of fluidnd proteins. Ultimately, tissue damage and skin breakdownccur and an ulcer develops. Tissue damage stimulates theelease of chemical mediators of inflammation-sensitizingeripheral somatic pain receptors, instigating transmissionf pain from the area.

Pain management for tissue-damage wounds relies onystemic analgesics. A protocol based on the guidelines ofhe World Health Organization (WHO) analgesic ladder is

sed. This protocol advocates a tiered approach by which

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ess potent medications are instituted first, until the patients comfortable and experiences minimal side effects. Whenower tier drugs prove ineffective, the next higher tier med-cations are added to the regimen in a stepwise fashion.irst-tier medications include nonopioids, such as NSAIDsnd tricyclics. Second-level medications include drugs withpioids in combination with acetaminophen or NSAIDs.hird-tier medications include all other opioids, both shortnd long acting [4]. By using combinations of medica-ions—for example, opioids, NSAIDs, tricyclics, and some-imes anticonvulsants—that act on different parts of the painathway, an additive/synergistic effect can be achieved.ast-onset, short-duration medications (frequently opioids)re added to treat episodic breakthrough pain.

This patient had a painful venous ulcer with the possibleddition of diabetic or ischemic neuropathic pain. His painas not controlled adequately on first- and second-tier an-

lgesics from the WHO ladder. Therefore, we developed ahronic analgesic regimen for him with an extended-releasepioid fentanyl patch. The patch provided continuous re-ease of the opioid transdermally, and the medication wasaintained at steady analgesic blood levels, maximizing

nalgesia and minimizing side effects. The slow-releaseechanism of the fentanyl transdermal delivery system

changed every 72 hours) facilitates patient compliance androvides safe delivery of a potent analgesic. It also is asso-iated with less nausea. The COX-2 inhibitor, NSAID,esensitized peripheral nociceptors (pain receptors), and aricyclic antidepressant stimulated descending inhibitoryracts in spinal-cord pain pathways, which diminished theharp, shooting aspect of his neuropathic pain. An anticon-ulsant may be effective either at the peripheral or centralervous system level and, therefore, it also was used foreuropathic analgesia. The anticonvulsive decreased abnor-al firing that contributes to the burning sensation of neu-

opathic pain. To diminish breakthrough pain, the patientas treated with tramadol as required. Tramadol has opioid

nd tricyclic effects, and is beneficial to treat both theomatic tissue-damage pain and neuropathic pain.

europathic (diabetic) wound pain management

ase history

A 47-year-old, 300-lb man with a 5-year history ofIDDM had a 10-month history of bilateral foot pain andlceration. He described the pain as sharp and shooting inharacter, intermittent, and worse at night. A 1-cm ulcer wasoted on the medial aspect of his right hallux, as well aslanching erythema on the medial aspect of the left hallux.ensory examination demonstrated that diminished feelingas present in the distal distribution of L5 bilaterally. Put-

ing pressure on his feet while walking was extremely pain-ul. The patient was taking carbamazepine and gabapentin

or neuropathic pain, as well as Coumadin (warfarin so- c

ium; Bristol-Myers Squibb, Princeton, NJ) for cardiomy-pathy.

We initially started this patient on amitriptyline andxycodone/acetaminophen as needed, in addition to thearbamazepine and gabapentin. Oxycodone was effective inelieving pain, but its duration is short. Thus, he was givenxtended-release oxycodone and a lidocaine patch over thereas of neuropathic foot pain.

This patient required a series of lower-extremity intrave-ous Bier blocks with bretylium and lidocaine, a series ofilateral local anesthetic lumbar sympathetic blocks, andltimately required bilateral radiofrequency-lesioning lum-ar sympathetic blocks.

ase discussion

This patient had bilateral diabetic neuropathic pain withn ulcer caused primarily by pressure or injury. The painollowed a dermatomal distribution and was lancinating inature, which indicated an injury to a somatic nerve. Hy-eresthesia (an exaggerated response to stimuli) and allo-ynia (a painful response to nonpainful stimuli) are frequentndings in these types of patients. Pain can even occur inreas of sensory deficit, known as anesthesia dolorosa.

Neuropathies are caused by axonal degeneration andegmental demyelination. Patients with diabetes developschemic neuropathy secondary to microvascular changes inhe vasa nervosum, the blood supply to the nerve itself.schemia to the nerve selectively leads to a greater loss ofarge inhibitory fibers (eg, A�) than small stimulatory painbers (eg, A� and C). This differential injury increases painensation from the periphery. Changes at the levels of theorsal root ganglia, dorsal horn neurons, and brain itselflso have been associated with neuropathic pain [5].

The most well-established and most extensively studiedlass of medications used to treat neuropathic pain are thericyclic antidepressants. They inhibit serotonin and norepi-ephrine in the descending inhibitory pain tracts of thepinal cord. Amitriptyline has been studied extensively forreating neuropathic pain [6], but desipramine [7] and nor-riptyline also are effective with fewer anticholinergic sideffects.

Currently, anticonvulsants are probably the most com-only used medications to treat neuropathic pain. The first

nticonvulsants shown to be effective in treating neuro-athic pain were carbamazepine [8] and diphenylhydantoin9]. However, they both have a long list of side effects, soewer anticonvulsants, with far fewer complications, haveirtually replaced them. Gabapentin, a newer-generationnticonvulsant, also has been shown to be effective in mul-iple types of neuropathic pain, including diabetic neurop-thy [10].

Other classes of medications used to treat neuropathicain with varying success include mexiletene [11], capsa-cin [12], N-methyl-D-aspartate (NMDA) inhibitors [13],

lonidine [14], tramadol [15], and lidocaine patches [16].

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Opioids use to treat neuropathic pain are somewhat con-roversial. Clinically, analgesia is obtained with higher thanusual” dosages, which risks excessive side effects.SAIDs provide systemic analgesia for neuropathic pain asart of a chronic analgesic regimen but probably should bevoided in anticoagulated patients.

Also controversial is the use of sympathetic blocks for

ig. 1. This patient presented with excruciating pain that resulted in loss ofleep. (Top) The nonhealing wound located at a fracture site. This woundlowly closed using topical cadexomer iodine. A lidocaine patch was alsosed and resulted in a significant reduction in this patient’s pain. (Bottom)he healed wound. A typical example of where a wound physician andain physician collaborated to ensure comprehensive treatment that re-ulted in both wound closure and resolution of pain. In this case noebridement or culture of wound was needed.

iabetic neuropathic pain. The basis of this treatment relates

o microvascular stenosis, which causes ischemic neuritis.ympathetic blockade should improve this pathological sit-ation. The described patient received Coumadin. There-ore, the injection of choice included a regional lower-xtremity intravenous Bier block with bretylium, aympatholytic agent, and lidocaine (a local anesthetic) tovoid deep injections. When the series of Bier blocks failedo provide sustained relief, a series of local anesthetic and,ltimately, neurolytic radiofrequency-lesioning lumbarympathetic blocks were undertaken, after the patient’soumadin was stopped and the prothrombin time returned

o normal. Bretylium Bier blocks have a sympatholyticction and decrease the release of catecholamines fromerminal nerve endings. Lumbar sympathetic blocks inhibitympathetic transmission at the level of the sympatheticanglion. Using bretylium Bier blocks and lumbar sympa-hetic blocks together may be synergistic.

Epidural anesthesia by way of a percutaneous catheteray be considered in patients with bilateral neuropathic

isease but was not used in this patient because of thenticoagulation. Anticoagulation is a relative contraindica-ion for central axis injections. If sympathetic blocks areonsidered, Coumadin should be stopped 4 days before therocedure and a prothrombin time obtained to ensure ade-uate hemostasis.

ummary

The most efficient analgesia is obtained by treating thenderlying pathophysiology that causes the pain [17,18].his requires an understanding of the mechanisms of painnd an understanding of all the different modalities avail-ble to correct this pathophysiology. As demonstrated inig. 1, the wound-healing practitioner and pain-manage-ent expert must be in constant communication; each must

ave a basic knowledge of the other’s specialty to provideptimum care and reduce morbidity.

The critical factor in wound-pain management is first toscertain whether surgical debridement is necessary to cleanhe wound and promote healing, and then to find the mostffective combination of topical and systemic analgesia. Allain, regardless of cause, can be objectively diagnosed andreated. The patient should be assured that treatment effi-acy will be objectively measured and the analgesic treat-ent modified to obtain the best results.

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