naloxone and Multiple-Sclerosis

Pain in multiple sclerosis (MS) is more common than has previously been believed. About 28% of all MS patients suffer from central pain (CP), a pain that is difficult to treat. In the present study we have investigated the responsiveness of this pain to morphine. Fourteen opioid-free patients (eight woman and six men) with constant, non-fluctuating, long-lasting CP caused by MS were investigated. Placebo (normal saline), morphine and naloxone were given intravenously in a standardized manner. The study design was non-randomized, single blind and placebo controlled. Ten patients experienced less than 50% pain reduction by placebo and less than 50% pain reduction by morphine. Four patients were opioid responders, i.e. had minimal or no effect on pain by placebo, >50% pain reduction after morphine and >25% pain increase after naloxone, given intravenously following morphine. However, this response was obtained after high doses of morphine (43 mg, 47 mg, 50 mg and 25 mg; mean 41 mg). Thus, compared with nociceptive pain, only a minority of the patients with CP due to MS responded to morphine and only at high doses. The present results are in accord with experimental studies indicating that neuropathic pain is poorly responsive but not totally unresponsive to opioids. The results do not support the routine use of strong opioids in MS patients with CP.

Topics: Adult; Aged; Analgesics, Opioid; Central Nervous System; Controlled Clinical Trials as Topic; Dose-Response Relationship, Drug; Drug Tolerance; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morphine; Multiple Sclerosis; Naloxone; Narcotic Antagonists; Pain Measurement; Pain, Intractable; Single-Blind Method; Sleep Stages; Surveys and Questionnaires; Treatment Failure

Low dose naltrexone (LDN) has been evaluated in several small studies for the treatment of inflammatory conditions. It is thought to work through modulation of inflammatory mediators and upregulation of endogenous opioid receptors. This may hypersensitize patients to exogenous opioids. Drug-drug interaction screening tools built into electronic health records and other services identify the interaction as risk of opioid withdrawal rather than hypersensitivity. We present a case of a drug-drug interaction in a patient who was receiving LDN treatment of multiple sclerosis. The patient received a single dose of oxycodone 5mg that resulted in obtundation unresponsive to painful stimuli necessitating the administration of naloxone boluses and infusion along with admission to the intensive care unit for 1 night. The patient responded well to naloxone therapy. He was discharged in satisfactory condition.

Topics: Aged; Analgesics, Opioid; Disabled Persons; Dose-Response Relationship, Drug; Drug Interactions; Humans; Male; Multiple Sclerosis; Naloxone; Narcotic Antagonists; Opioid-Related Disorders; Oxycodone; Pressure Ulcer; Treatment Outcome

Previously, we demonstrated that electroacupuncture (EA) decreased lymphocyte infiltration into the spinal cords of rats presenting with experimental autoimmune encephalomyelitis (EAE), a disease model used in the study of multiple sclerosis (MS). The aim of this study was to characterize the effects of EA on the EAE. Female Lewis rats were divided into either CFA, EAE, EA, or injection with naloxone after electroacupuncture (NAL) groups. Electroacupuncture was administered every day for 21 days. To evaluate proliferation and apoptosis, lymphocytes from rats presenting with EAE were collected and cultured with β-endorphin. Immunohistochemisty, flow cytometry and radio-immunity methods were applied to detect the expression of β-endorphin. Results presented in this report demonstrate that the beneficial anti-inflammatory effects of EA on EAE were related to β-endorphin production that balances the Thl/Th2 and Th17/Treg responses. These results suggest that β-endorphin could be an important component in the development of EA-based therapies used for the treatment of EAE.

Topics: Animals; Apoptosis; beta-Endorphin; Cell Proliferation; Electroacupuncture; Encephalomyelitis, Autoimmune, Experimental; Female; Humans; Multiple Sclerosis; Naloxone; Rats; Rats, Inbred Lew; T-Lymphocytes, Regulatory; Th1-Th2 Balance; Th17 Cells

Topics: Analgesics; Dronabinol; Humans; Multiple Sclerosis; Naloxone; Narcotic Antagonists; Pain; Pain Measurement; Receptors, Opioid