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Management of Pain. C. Brian Warriner, MD, FRCPC Professor and Chair UBC Department of Anesthesiology, Pharmacology and Therapeutics brian.warriner@vch.ca. Management of Pain. Agenda: Definitions Pathophysiology Analgesics Gases (N 2 O) Opiates NSAID’s Acetaminophen

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Management of Pain

C. Brian Warriner, MD, FRCPC

Professor and Chair

UBC Department of Anesthesiology, Pharmacology and Therapeutics

brian.warriner@vch.ca


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Management of Pain

  • Agenda:

    • Definitions

    • Pathophysiology

    • Analgesics

      • Gases (N2O)

      • Opiates

      • NSAID’s

      • Acetaminophen

      • Phencyclidine – derivatives (NMDA antagonists)

      • Alpha2-adrenergic agonists


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Management of Pain

  • Agenda (continued)

    • Analgesics

      • Local anesthetics – combination therapy

      • Modes of delivery

        • Oral

        • Rectal

        • Systemic

        • Neuraxial

    • Modes of Delivery – Case reports

    • Obstetrics


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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


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Management of Pain

  • Descriptors:

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


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Management of Pain

  • The Pain Team:

    • The patient

    • Nurses (nurse-clinician)

    • Anesthesiologist

    • Clinical pharmacologist

    • Psychiatrist

    • Pharmacist

    • Psychologist

    • Physiotherapist

    • Occupational therapist

    • Radiologist

    • Neurosurgeon

    • Social worker

    • The family

    • Pastoral care

    • Obstetrical pain: patient, partner, coach, midwife, obstetrician


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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


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Management of Pain

Pathophysiology

of Pain


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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


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Management of Pain

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

  • Opiate receptors are mu, delta and kappa


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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


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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


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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


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Management of Pain

  • Neuropathic pain:

    • Injury to peripheral nerves and CNS can lead to functional and structural changes in the pathways

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

    • Flitting, shock-like pain

    • Often very difficult to treat


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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)


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Management of Pain

  • Opioid receptor agonists:

    • Morphine

    • Heroin

    • Meperidine

    • Codeine

    • Oxycodone

    • Hydromorphone

    • Fentanyl

    • Sufentanil

    • Remifentanil, alfentanil

    • methadone


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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


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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


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Management of Pain

  • Opioid receptor agonists:

    • Many dosage forms:

      • Oral, transmucosal

      • Inhalation

      • Subcutaneous

      • Intramuscular

      • Intravenous (continuous, intermittent, PCA)

      • Intra-thecal

      • epidural


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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


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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 and ER physicians


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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


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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


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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


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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


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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


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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


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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


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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


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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.


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Management of Pain

  • Alpha2-agonists:

    • Clonidine

    • Can be given orally or neuraxially

    • Sedation, severe postural hypotension, very dry mouth


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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


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Management of Pain

  • Local anesthetics as an adjunct to opiates:

    • Neuraxial analgesia

      • Sub-arachnoid (spinal)

      • Epidural

    • loss of sensation, muscle weakness, hypotension


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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


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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?



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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?



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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?


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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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Obstetrical Pain 01:15 AM)

  • 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


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Obstetrical Pain 01:15 AM)

  • 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


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Obstetrical Pain 01:15 AM)

  • 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


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Recent Developments 01:15 AM)

  • 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


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Management of Pain 01:15 AM)

  • brian.warriner@vch.ca


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