Management of PainPCTH 325

C. Brian Warriner, MD, FRCPCProfessorUBC Department of Anesthesiology, Pharmacology and Therapeuticsbrian.warriner@vch.ca

Management of Pain

• Agenda:

– Definitions

– Pathophysiology

– Analgesics

• Gases (N2O)

• Opiates

• NSAID’s

• Acetaminophen

• Phencyclidine – derivatives (NMDA antagonists)

• Alpha2-adrenergic agonists

Management of Pain

• Agenda (continued)– Analgesics

• Local anesthetics – combination therapy

• Modes of delivery– Oral

– Rectal

– Systemic

– Neuraxial

– Modes of Delivery – Case reports

– Obstetrics

Management of Pain

• Definition:

– Oxford Pocket Dictionary

• Strongly unpleasant bodily sensation such as is caused by illness or injury

• Mental suffering or distress

• Vulgar as in “pain in the neck” or other anatomical areas

• Great cares or troubles

• Verb (idiomatic) – to pain

Management of Pain

• Descriptors:

– Sharp, crushing, burning, cramping, gassy, throbbing, cutting, aching, dull, deep, pinching, slashing, pin-point, continuous, spasm, tearing, lancing, knifing, etc…

Management of Pain

• The Pain Team:– The patient– Nurses (nurse-clinician)– Anesthesiologist– Clinical pharmacologist– Psychiatrist– Dentist– Pharmacist– Psychologist– Physiotherapist– Occupational therapist– Radiologist– Neurosurgeon– Social worker– The family– Pastoral care– Obstetrical pain: patient, partner, coach, midwife, obstetrician

Management of Pain

• Incidence:

– Appears to be independent of race, culture, economic status

– 30% of adults have “chronic pain” at any given time

– 12% have severe pain

– 2% have disabling pain

– 80,000 British Columbians have disabling pain –more common that cancer or heart disease

Management of Pain

Pathophysiology

of Pain

Management of Pain

• Pain neurotransmission – simplified – Nociceptive receptors in periphery respond

to pH, ATP, and ligands to create afferent nerve conduction to dorsal root ganglia, dorsal horn of the spinal cord, brainstem, thalamus, hypothalamus, and cortex

– Modulation occurs at all levels and is mediated by opioid peptides, norepinephrine, glycine, and GABA

Management of Pain

• Opioid peptides inhibit synaptic transmission at several sites: beta-endorphin, enkephalins, dynorphins.

• Opiate receptors are mu, delta and kappa

Management of Pain

• Opioids produce analgesia because of their actions in the brain, brainstem, spinal cord, and peripheral terminals of primary afferent nerves.

• Brain: Alter mood in response to pain

• Brainstem: stimulate release of inhibitory signals

• Spinal cord: inhibit primary afferent activity

• Peripheral sites: inhibit afferent response

Management of Pain

• Types of Pain:– Acute – severe but usually managed with

opioids, NSAID’s, acetaminophen, local anesthetics

– Transitional: not easily diagnosed, needs aggressive treatment to prevent transition to chronic

– Chronic: long-lasting, difficult to treat, personality changes, drug seeking

Management of Pain

• Complex regional pain syndromes:– Previously called reflex sympathetic dystrophy

– Transitional to chronic in nature

– Can be initiated by relatively minor insults

– Peripheral sensitization resulting in allodynia and hyperalgesia

– Requires very aggressive team approach to therapy

– Can result in completely non-functional limb requiring amputation

Management of Pain

• Neuropathic pain:

– Injury to peripheral nerves and CNS can lead to functional and structural changes in the pathways (concept of plasticity)

– Nerve regeneration after injury can produce a nidus of intense pain

– Flitting, shock-like pain

– Often very difficult to treat

Management of Pain

• Classes of Drugs:

– Opioid receptor agonists

– Non-steroidal anti-inflammatory drugs

– Tri-cyclic antidepressants

– Anti-convulsants

– NMDA receptor antagonists

– Alpha2- agonists

– 5HT1-agonists for migraine

– Gases (N2O)

Management of Pain

• Opioid receptor agonists:– Morphine– Heroin – Meperidine– Codeine– Oxycodone– Hydromorphone– Fentanyl– Sufentanil– Remifentanil, alfentanil– methadone

Management of Pain

• Opioid receptor agonists:– Act on mu-receptors to produce both

effects and side-effects – brain, brainstem, spinal cord, and peripheral terminals

– Side effects: respiratory depression, nausea and vomiting, constipation, sedation, dizziness, euphoria, confusion, muscle rigidity, pruritus

– Physical and psychological dependence

Management of Pain

• Opioid receptor agonists:– Tolerance can develop quickly (in a matter

of minutes with remifentanil)

– Morphine is the reference opioid – used primarily for treatment of acute pain –injury, surgery, acute abdomen, etc

– Primary metabolism is in liver and oral morphine is rapidly reduced by first-pass metabolism

Management of Pain

• Opioid receptor agonists:– Many dosage forms:

• Oral, transmucosal

• Inhalation

• Subcutaneous

• Intramuscular

• Intravenous (continuous, intermittent, PCA)

• Intra-thecal

• epidural

Management of Pain

• Opioid receptor agonists:

– Codeine – methyl-morphine – rapidly converted to morphine by the liver – effective orally and intramuscularly – commonly used as antitussive and mild analgesic

– Heroin – converted to morphine by liver – no real therapeutic advantage over morphine – addicted claim it produces more euphoria than morphine but studies inconclusive

Management of Pain

• Opioid receptor agonists:

– Meperidine (Demerol) – first synthetic opioid – 1/10th potency of morphine

– Less Sphincter of Vater spasm

– Fentanyl – 100 times potency of morphine – intermediate duration – intravenous –used primarily by anesthesiologists, ER and pain physicians

Management of Pain

• Opioid receptor agonists:– Sufentanil – 1000 times potency of

morphine – intermediate duration – used only by anesthesiologists

– Remifentanil – 70 times potency of morphine – very short duration of action -metabolized by ester hydrolysis in plasma –given only by continuous intravenous infusion by anesthesiologists

Management of Pain

• Opioid antagonists:

– naloxone – very rapid reversal of opioid effects – given IV by ER physicians and anesthesiologists

– Naltrexone – longer acting antagonist used in treatment of both opioid addiction and alcoholism

Management of Pain

• Non-steroidal anti-inflammatories

– ASA and others of same class

– Ibuprofen is a relatively low potency, short acting example of the family

– Inhibit the action of cyclooxygenase enzymes (COX-1 and COX-2) and reduce the production of prostaglandins

Management of Pain

• NSAID’s :

– Analgesia by reducing prostaglandin synthesis

– Reduce the recruitment of leukocytes which produce inflammatory mediators

– Directly inhibit the release of prostaglandins in the dorsal horn

Management of Pain

• NSAID’s:– Side effects: gastric hemorrhage, platelet

dysfunction, renal toxicity

– Specific drugs:• ASA – relatively short acting, little negative

effect upon kidney

• Acetaminophen – reduces central prostaglandin synthesis – no real anti-inflammatory effect –no renal effects – overdose can cause acute liver failure

Management of Pain

• NSAID’s:

– Specific drugs:

• Ibuprofen – relatively short acting

• Naproxen, ketorolac (systemic), diclofenac, and others –relatively long acting – all have negative renal and gastric effects – likely also have cardiac effects

• COX-2 inhibitors were introduced with the expectation of fewer side effects (particularly gastric) but caused increased incidence of ischemic cardiac events and were withdrawn from the market

Management of Pain

• Antidepressants:

– Tri-cyclics

– Increase norepinephrine and serotonin activity in spinal cord

– Activate depressed chronic pain patients

– Diabetic neuropathy and post-herpetic neuralgia

– Amitriptyline, nortriptyline and imipramine

Management of Pain

• Anticonvulsants:

– Reduce neuronal excitability

– Gabapentin, carbamazepine

– Chronic pain management

– Diabetic neuropathy

– Trigeminal neuralgia

– Dizziness, somnolence, confusion, ataxia

– Pre-gabalin new member of this class – fewer side effects –heavily marketed – efficacy???

Management of Pain

• NMDA receptor antagonists:

– Reduce central sensitization due to increased NMDA

– Ketamine (phencyclidine relative) – general anesthetic agent which, in small doses, is an effective analgesic

– Used occasionally for labour analgesia and analgesia prior to surgery.

Management of Pain

• Alpha2-agonists:

– Clonidine, dextrometomodine

– Can be given orally or neuraxially

– Sedation, severe postural hypotension, very dry mouth

Management of Pain

• 5HT1-agonists: (sumatriptan)

– For the treatment of migraine headaches

– Vasoconstriction and prevention of central sensitization

– Vasoconstriction can increase risks in other vascular beds such as the cardiac

Management of Pain

• Local anesthetics as an adjunct to opiates:

– Neuraxial analgesia

• Sub-arachnoid (spinal)

• Epidural

– loss of sensation, muscle weakness, hypotension

Management of Pain

• Modes of delivery:

– Oral – most drugs

– Rectal – acetaminophen, NSAID’s, ASA

– IM or IV – opiates, ketorolac (NSAID) –patient controlled analgesia (PCA)

– Neuraxial – opiates, clonidine, local anesthetics

– Percutaneous – fentanyl patch

Management of Pain

• Case 1:

– A 27 year old male is in a fight and appears in the ER with severe abdominal pain and evidence of internal damage. He asks for pain relief. What would you do?

Management of PainPCA

Management of Pain

• Case 2:

– A 60 year old woman is admitted to the hospital with cancer of the lung. She requires a lobectomy. This is associated with very severe post-operative pain. What can be done to help?

Management of PainEpidural

Management of Pain

• Case 3:

– A 62 year old woman complains of continuous nagging, aching pain over her back and legs. Neurological and musculo-skeletal exam are essentially normal except for reduced range of motion of the back and lower limbs. How should her pain be managed?

Obstetrical Pain

• Each patient has a unique labour pain experience

• Labour pain is mediated from t10 – l1• Intermittent, increasing in intensity,

very severe

• Delivery pain is mediated from S2,3,4 and tends to be continuous or nearly so

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© 2005 Elsevier

Downloaded from: Miller's Anesthesia (on 27 November 2006 01:15 AM)

© 2005 Elsevier

Obstetrical Pain

• Pain varies greatly from patient to patient and pregnancy to pregnancy

• Modes:– Psycho-prophylaxis – breathing, relaxation

exercises

– Massage, baths, acupuncture

– Nitrous oxide – demand valve respirator for period during contraction only – effective analgesic but of only intermediate potency – can cause sedation, confusion

Obstetrical Pain

• Modes:– Intravenous narcotics: different effects on

Mom and babe – potential for respiratory depression in new born

– Ketamine – effective in small doses but effect short-lived and larger doses can cause neuro-psychiatric effects

– Intramuscular narcotics – same problems as IV but longer lasting

Obstetrical Pain

• Modes:– Epidural – continuous infusion of local

anesthetic (dilute) and opioid (usually fentanyl) – can cause reduced muscle strength and loss of urge to push – slows down early stages of labour but probably quickens entire labour time (controversial)

– Various potential complications associated with the procedure

Recent Developments

• May, 2008 - British Columbia 1st province to include “chronic pain” as separate disease entity under the common heading of “chronic diseases” – allows funding for research and treatment to be released by Ministry of Health

• October 31, 2008 – BC Pain Society approved by BC Legislature

• July, 2014 – start of pain residency

Management of Pain

• brian.warriner@vch.ca