Pain for the Rheumatologist

Opioid Use In Rheumatic Disease Maurice Kinsolving MD PRA Annual Meeting April 22 - 25, 2004 Palm Springs, California Types of Pain ✴ Nociceptive ✴transient pain from noxious stimuli ✴ Inflammatory ✴from tissue damage/inflammation ✴ Neuropathic ✴spontaneous and hypersensitivity associated with damage to the nervous system ✴ Functional ✴hypersensitivity resulting from abnormal central processing of normal input Woolf, C. J. Annals Int Med 2004; 140(6): 441-451 Adaptive vs Maladaptive Pain ✴ Adaptive ✴nociceptive almost always ✴inflammatory mostly ✴ Maladaptive ✴inflammatory sometimes ✴neuropathic ✴functional Treatment Options for Chronic Pain ✴ NSAIDS: salicylates to cox-2 specific ✴ TCAs: nortryptiline ✴ Topical agents: capsaicin, lidocaine gel/patch ✴ Anticonvulsants: tegretol, gabapentin ✴ Opioids: morphine Opioids in Chronic Painful Rheumatic Syndromes ✴ Chronic pain in rheumatic disease is common ✴ Therefore long term use of pain medication is common ✴ Opioids are generally the gold standard for treating pain ✴ The debate has been whether opiates are the correct choice for treating chronic pain ✴the minority view is that opiates have a minimal effect on functioning and may worsen outcome ✴key organizations including the Federation of State Medical Boards support the use of opiates in chronic pain Requirements for Opioid Use ✴ Comprehensive history & exam ✴ Establish that other therapies have been inadequate ✴ Clearly review risks and benefits with the patient ✴ Establish a contract with the patient ✴ Establish a follow up program with the patient ✴same physician ✴same pharmacy ✴monitor for signs of abuse ✴ Document thoroughly all of the above Study Support for Opioid Use ✴ General finding is that patients with chronic pain can achieve reasonable pain control using a stable dose of opiate with minimal risk of addiction ✴ Surveys & uncontrolled case series ✴ Treatment up to 6 years ✴ Moderate doses mostly: 195 mg morphine equivalent/d ✴to 360 mg in 52 patients ✴to 2 grams in 23 patients ✴ Cognitive function including driving preserved ✴impaired for 1 week after a dose increase Ballantyne, J. C. et. al. N Engl J Med 2003;349:1943-1953 Prolonged Hi Dose Opioids ✴ Principles ✴increase to maximal analgesia with minimal side effects ✴make increases over weeks ✴use moderate doses ✴increase doses later only with caution ✴ Practice ✴generally more liberal ✴doses often 1 gm + per day ✴anecdote suggests hi doses rarely result in satisfactory analgesia or improved function ✴ Evidence suggests doses should be limited to maintain both efficacy and safety Opioid Tolerance ✴ Develops with repeated use ✴ Requires increased dose for same analgesic effect ✴ Two general types ✴Associative or learned tolerance ✴may be seen in addicts admitted to hospital and exhibit a marked reduction in opioid tolerance ✴Nonassociative or adaptive tolerance ✴down-regulation or desensitization of opioid receptors ✴ Involve different neurotransmitter mechanisms Adverse Effects ✴ Opioid-induced abnormal pain sensitivity ✴ Opioid-induced hormonal changes ✴ Opioid-induced immune modulation Opioid -Induced Abnormal Pain Sensitivity ✴ Hyperalgesia ✴increased tenderness from noxious stimuli ✴ Allodynia ✴pain from previously innocuous stimuli ✴ Both of these may occur with long-term use of opioids ✴ Mechanism may be similar to that which occurs in neuropathic pain ✴ NMDA (N-methyl-D-aspartate)-receptor involved ✴ Can involve irreversible neurotoxic changes including apoptosis Abnormal Pain Sensitivity con’t ✴ Repeated administration of opioids may lead to a pro-nociceptive or sensitization to pain process ✴ Desensitization to opioids or tolerance to opioids together with sensitization to pain may lead to dose escalation ✴ Difficult to determine whether “apparent” tolerance is ✴opioid tolerance ✴abnormal pain sensitivity ✴disease progression Hormonal Changes ✴ HPA (hypothalamic-pituitary-adrenal axis) ✴strong progressive decline in plasma cortisol levels ✴ HPG (hypothalamic-pituitary-gonadal axis) ✴increased prolactin ✴decreased LH, FSH, testosterone, estrogen ✴ Collective effects may include: ✴decreased libido ✴amenorhea ✴galactorhea ✴ Extreme example: men receiving intrathecal opioids need testosterone replacement Immune Modulation ✴ Opioid receptors are found on cells of the immune system ✴ Prolonged exposure appears to suppress immune function ✴ Abrupt withdrawal of opioids may induce immunosuppression ✴ Pain as well can be immunosuppressive, so the problem is the patient who is on high doses without relief of pain Possible Adverse Effects of Prolonged Opioid Therapy Ballantyne, J. C. et. al. N Engl J Med 2003;349:1943-1953 Dose Limits ✴ Ceiling dose? ✴ Study data only to about 180 mg/d morphine ✴ Rather than a number it may be simply recognizing that continuing dose escalation for more than 2 months suggests a problem ✴ Next figure suggests a protocol to follow Suggested Protocol for Opioid Therapy Ballantyne, J. C. et. al. N Engl J Med 2003;349:1943-1953 Choice of Opioids ✴ See the following table ✴ No evidence that dosing regimen has any bearing on the development of tolerance ✴ Avoid opioids in fixed dose with aspirin or tylenol ✴ Generally long-acting formulations are preferred ✴ Methadone may be a good choice because ✴long-acting and has NMDA-receptor antagonism ✴ Methadone may be a bad choice because ✴half-life is unpredictable and it may accumulate ✴ American Society of Anesthesiologists recommends the slow-release forms of morphine and oxycodone Opioid rotation ✴ Some variability in opioid receptors suggests that some variation in response to various opioids may exist ✴ A second opiate may be started at half the equivalent dose ✴ Methadone may be particularly helpful in rotation since the patient already tolerant and unlikely suffer respiratory depression and ?related to it’s NMDA-receptor properties Failure of Continued Dose Escalation ✴ May need to wean the patient and re-assess ✴ It may take three months off opioids to make an accurate assessment ✴ The patient may decide they prefer not to be on opiates once they overcome the fear of living without opiates ✴ Those patients with no improvement off can be restarted on much lower doses Opioid-seeking Behavior ✴ Rule out inadequate analgesia ✴ Non-compliance versus addiction ✴ Diversion ✴ Addiction may be masked if the physician complies with the patient’s unreasonable demands ✴ Features reviewed in the following table Ballantyne, J. C. et. al. N Engl J Med 2003;349:1943-1953 Conclusions ✴ Re-assess regularly for true improvement in both pain and functioning in patients on chronic opiates ✴ Use a cautious approach to dose escalation ✴ Prolonged high dose opioids may be neither safe nor effective in some patients ✴ Consider discontinuation if treatment goals are not met References Ballantyne, J. C. et. al. N Engl J Med 2003;349:1943-1953 Nicholson, B. Drugs 2003; 63(1): 17-32 Woolf, C. J. Annals Int Med 2004; 140(6): 441-451 Guide to Chronic Pain Assessment & Management in Primary Care 2002; Care Management Institute