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

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Management of Pain

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management of pain

Management of Pain

C. Brian Warriner, MD, FRCPC

Professor and Chair

UBC Department of Anesthesiology, Pharmacology and Therapeutics

management of pain2
Management of Pain
  • Agenda:
    • Definitions
    • Pathophysiology
    • Analgesics
      • Gases (N2O)
      • Opiates
      • NSAID’s
      • Acetaminophen
      • Phencyclidine – derivatives (NMDA antagonists)
      • Alpha2-adrenergic agonists
management of pain3
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…
management of pain6
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


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?
obstetrical pain
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
  • 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
  • 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
  • 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
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
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Management of Pain