1. Pain Management EO 004.12

2. Learning Objectives Describe the principles of pain management for acute and chronic pain that impact on patient care Select the most appropriate analgesic for an individual patient to maximize the benefits that can be expected from therapy Communicate important aspects of analgesic therapy to patients to improve the odds of therapy being successful

3. References Therapeutic Choices –Chapters 11,12 Current Medical Diagnosis and Treatment –Chapters 20, 24

4. Outline Pain Definitions Epidemiology Pathophysiology Pain Pathways Drug Treatment Mild Analgesics Opioid Analgesics Adjuvant Analgesics Miscellaneous Analgesics Cases

5. Pain Definitions What is pain? What purpose does pain serve? How can I assess an individual’s pain? What are the implications of poorly managed pain?

6. Analgesia, Anesthesia And Pain Analgesia Anesthesia Pain 1.Acute 2.Chronic 3.Neuropathic 4.Bone 5.Palliative Care

7. Acute And Chronic Pain

8. Somatic, Visceral And Neuropathic Pain

9. Pain Epidemiology - Overview Fifty million Americans are partially or totally disabled because of pain Fifty percent of seriously ill hospitalized patients report pain (15% had moderate to severe pain at least 50% of the time) Seventy percent of chronic pain patients in nursing homes had pain despite treatment Fifty percent of people in a British study of community-dwelling patients had pain (in 50% of those the pain was significant)

10. Epidemiology – Neuropathic Pain

11. Pain pathways Ascending stimulating pathways –Noxious stimulus activates afferent neurons A  fibres – fast transmission, sharp stinging – acute pain C fibres – slow transmission, dull, aching – chronic pain –Stimulate the CNS via spinal interneurons Substance P and Glutamate

12. Pain Pathways Descending inhibitory pathways –Originate in midbrain –Release inhibitory neurotransmitters Serotonin and norepinephrine Enkephalins Gate hypothesis –Pain transmission up the ascending pathway can be modulated by activity of other neurons

13. Pain Perception Nociceptive process Physiologic response Emotional response Psychological framework

14. Assessing Pain Provocative causes/Palliative aids Quality Radiation Severity Timing

15. An Approach To Acute Pain Patient (pt) has pain or is likely to have pain Critical first step: detailed history and focused physical exam Determine mechanism of pain – pt may report more than one type Arrange diagnostic workup and treat pain per information available Next page

18. An Approach To Chronic Pain

19. Approach To Chronic Pain

21. Assessing An Individual’s Pain

23. Analgesics Mild –Acetaminophen, ASA, NSAIDS Opiates –Moderate – codeine –Severe - morphine, meperidine and others Adjuvants –Tricyclic Antidepressants (TCAs) –Anti-Epileptic Drugs (AEDs) Miscellaneous –Local Anesthetics, Capsaicin, Cannabis

24. Acetaminophen Works by inhibiting the synthesis of prostaglandins in the central nervous system and peripherally by blocking pain impulse generation Has no significant anti-inflammatory effects Is most responsive to somatic type pain of mild to moderate intensity Has an opioid sparing effect when used in combination with narcotics

25. ASA Works by irreversibly acetylating cyclooxygenase (COX) to inhibit prostaglandin synthesis Similar efficacy, potency, and time-effect curve as acetaminophen Is most responsive to somatic type pain of mild to moderate intensity Largely replaced by equally or more effective but safer NSAIDs for most analgesic indications

26. NSAIDs NSAIDs are indicated for mild to moderate pain, especially if there is an inflammatory or boney component NSAIDs work by non-covalently binding to COX There is a high inter-patient variability in response to NSAIDs, so a trial of a different NSAID may be appropriate if a patient doesn’t respond to an initial course In single full doses, most NSAIDs are more effective than A.S.A. or acetaminophen and some have shown equal or even greater analgesic effect than usual doses of oral opioids

27. Mild Analgesics – Summary Benefits: 1.Useful for mild to moderate somatic pain 2.Well tolerated 3.Available in many forms 4.Low abuse potential Limitations: 1.Ceiling effect 2.Not useful for more severe pain, especially neuropathic or visceral type pain 3.Frequently require multiple daily doses for analgesia

28. Opioids - Background Opioids are used for all types of moderate to severe pain but are most effective for visceral and somatic pain – much less so for neuropathic pain, often necessitating adjuvant therapies Opioids do not decrease sensitivity to touch, sight or hearing at therapeutic doses

29. Opioids – Summary

30. Opioids –Benefits And Limitations Benefits: 1.Useful for moderate to severe pain of somatic or visceral origin 2.No ceiling effect for most agents 3.Available in many forms, including extended release 4.Predictable adverse effect profile Limitations: 1.Not as efficacious vs. neuropathic pain 2.Titration required due to physical tolerance 3.Numerous adverse effects including physical and psychological dependence 4.Special prescribing and dispensing practices may apply

31. TCAs – Background These medications are used as complementary therapy to primary analgesics in neuropathic pain Meta-analyses indicate TCAs are approximately 50% effective for patients with a number of painful neuropathic conditions TCAs are first line due to low cost and efficacy when the alternatives like AEDs are considered (although there are exceptions; notably trigeminal neuralgia)

32. TCAs - Indications Pain syndromes responsive to TCAs include: 1.Post-herpetic neuralgia 2.Peripheral neuropathy (i.e. diabetic neuropathy, HIV neuropathy, idiopathic neuropathy, etc) 3.Central pain (damage specifically to the brain or spinal cord from strokes, multiple sclerosis, limb amputations or trauma)

33. TCAs - MOA Postulated mechanisms include: 1.Blockade of norepinephrine, 2.Antagonism of histamine and muscarinic cholinergic receptors, 3.Alpha-adrenergic blockade, or 4.Suppression of C-fiber afferent-evoked activity in the spinal cord

34. AEDs – Background These medications are used as complementary therapy to primary analgesics in neuropathic pain Meta-analyses indicate AEDs, although widely used in chronic pain (approximately 5% of all AEDs prescribed in the U.S. are for pain management), have surprisingly few trials to show analgesic effectiveness

35. AEDs – Background There is no evidence AEDs are effective for acute pain In chronic pain syndromes other than trigeminal neuralgia, AEDs should be withheld until other interventions are tried Number-needed-to-harm for major effects weren’t significant for any drug vs. placebo Number-needed-to-harm for minor effects ranged from 2.5 (confidence interval [CI] 2.0- 3.2) for gabapentin to 3.7 (CI 2.4-7.8) for carbamazepine

36. AEDs - Indications AEDs have different indications Carbamazepine is the intervention of choice for trigeminal neuralgia Pain syndromes AEDs are used in include: 1.Trigeminal neuralgia 2.Peripheral neuropathy 3.Central pain 4.Post-herpetic neuralgia 5.Complex regional pain syndrome (formerly reflex sympathetic dystrophy)

37. AEDs - MOA The precise mechanism of action of AEDs remains uncertain The standard explanations include 1.Enhanced gamma-aminobutyric acid (GABA) suppression 2.Stabilization of neural cell membranes or possibly 3.Action via N-methyl-D-aspartate (NMDA) receptor sites

38. AEDs – Summary

39. Adjuvant Analgesics – Summary Benefits: 1.May improve pain control in conditions resistant to other analgesics 2.May allow for dosage reduction of other analgesics 3.Can be used in the long term management of chronic pain and associated conditions (i.e. depression) Limitations: 1.Not effective for acute pain 2.Not useful as monotherapy 3.Poor evidence supporting use in many conditions 4.Adverse effects often occur before therapeutic effects

40. Local Anesthetics Can provide relief of acute or chronic pain Are administered by injection (into the joints, epidural or intrathecal space, along nerve routes or in a nerve plexus) or topically (ex. lidocaine jelly, eutectic mixtures of local anesthetics [EMLA ® = lidocaine and prilocaine]) Work by blocking nociceptive transmission and interrupting sympathetic reflexes Are often combined with opioids for synergy

41. Local Anesthetics Disadvantages in the use of local anesthetics include: 1.Need for skillful technical application 2.Need for frequent administration 3.Need for highly specialized monitoring and follow-up procedures

42. Capsaicin Indicated in the topical treatment of pain associated with postherpetic neuralgia, arthritis, diabetic neuropathy and postsurgical pain May also be useful for psoriasis, chronic neuralgias unresponsive to other treatments and intractable pruritus

43. Capsaicin Commonly available as a cream of differing strengths: Zostrix ® = 0.025% Zostrix-HP ® = 0.075% Induces the release of substance P from peripheral neurons and after repeated application depletes substance P and prevents it’s reaccumulation

44. Capsaicin Onset of action = 14-28 days with regular application (3-4 times daily) Maximum effect may take up to 6 weeks Duration of effect after an application = several hours Transient burning occurs in > 30% of patients, which usually diminishes with repeated use Also causes itching, stinging, erythema and cough in 1-10% of patients

45. Cannabis Three quarters of British doctors surveyed in 1994 wanted cannabis available on prescription Humans have cannabinoid receptors in the central and peripheral nervous system Cannabinoids are analgesic and reduce signs of neuropathic pain in animal tests Some evidence suggests that cannabinoids may be analgesic in humans

46. Cannabis No studies have been conducted on smoked cannabis The predominant adverse effect was central nervous system depression which was common at higher doses Cardiovascular effects were generally mild and well tolerated

47. Cannabis The best that can be achieved with single dose cannabinoids is an analgesic effect equivalent to 60mg of codeine (or a number needed to treat of 16 patients for at least a 50% reduction in pain) Cannabinoids widespread introduction for pain management is therefore undesirable

48. Conclusion

49. A Bill Of Rights I have the right to have my reports of pain accepted and acted on by health care professionals I have the right to have my pain controlled, no matter what the cause or how severe it may be I have the right to be treated with respect at all times. When I need medication for pain, I should not be treated like a drug abuser

50. Principles Of Pharmacotherapy Always ask the patient if pain is present and assess the characteristics of pain Identify the source of pain Select the most effective analgesic with the fewest adverse effects Properly titrate the dose for each individual and administer for an adequate duration

51. Principles Of Pharmacotherapy Always consider around-the-clock (ATC) regimens for acute and chronic pain Use as-needed (PRN) regimens for breakthrough pain or when acute pain displays great variability and/or has subsided greatly Assess for adverse effects, particularly the constipation seen with opioids

52. Principles Of Pharmacotherapy Avoid excessive sedation by titrating opioids effectively Adjust the route of administration to meet the needs of the patient Whenever possible use the oral route When converting from one opioid to another, use the equianalgesic dose and then titrate

53. Principles Of Pharmacotherapy Do not use placebo therapy to diagnose psychogenic pain Consider the use of capsaicin, tricyclic antidepressants and anticonvulsants when treating neuropathic pain Use a multidisciplinary approach and nonpharmacologic strategies when possible

54. Pitfalls In Analgesic Therapy 1.Overestimating the analgesic efficacy of a drug 2.Underestimating the analgesic requirement of the patient 3.Prejudice against the use of analgesics that may prevent objective therapy 4.Lack of knowledge in analgesic pharmacology

55. Pitfalls In Analgesic Therapy 5.Patient non-compliance because of fear of addiction 6.Patient not communicating with caregivers for fear of being labeled a drug addict 7.Patient wants to please by not complaining 8.Patient does not know how or is afraid to communicate with caregiver