Effects of naltrexone on pain sensitivity and mood in fibromyalgia: no evidence for endogenous opioid pathophysiology

Jarred W Younger, Alex J Zautra, Eric T Cummins, Jarred W Younger, Alex J Zautra, Eric T Cummins

Abstract

The pathophysiological mechanisms underlying fibromyalgia are still unknown, although some evidence points to endogenous opioid dysfunction. We examined how endogenous opioid antagonism affects pain and mood for women with and without fibromyalgia. Ten women with fibromyalgia and ten age- and gender-matched, healthy controls each attended two laboratory sessions. Each participant received naltrexone (50mg) at one session, and placebo at the other session, in a randomized and double-blind fashion. Participants were tested for changes in sensitivity to heat, cold, and mechanical pain. Additionally, we collected measures of mood and opioid withdrawal symptoms during the laboratory sessions and at home the night following each session. At baseline, the fibromyalgia group exhibited more somatic complaints, greater sensory sensitivity, more opioid withdrawal somatic symptoms, and lower mechanical and cold pain-tolerance than did the healthy control group. Neither group experienced changes in pain sensitivity due to naltrexone administration. Naltrexone did not differentially affect self-reported withdrawal symptoms, or mood, in the fibromyalgia and control groups. Consistent with prior research, there was no evidence found for abnormal endogenous opioid activity in women with fibromyalgia.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow diagram of study procedures.
Figure 1. Flow diagram of study procedures.
Study procedures conducted on each participant, once with naltrexone, and once with placebo. SOWS = Subjective Opioid Withdrawal Scale; PANAS = Positive and Negative Affect Schedule; QST = Quantitative Sensory Testing.
Figure 2. Effects of naltrexone on self-reported…
Figure 2. Effects of naltrexone on self-reported opioid withdrawal symptoms.
Self-reported opioid withdrawal symptoms at 0 hours, 2 hours, and 8 hours (home measurement) after drug and placebo administration in Fibromyalgia patients (FM) and healthy controls (HC).

References

    1. Yunus MB. Towards a model of pathophysiology of fibromyalgia: aberrant central pain mechanisms with peripheral modulation. J Rheumatol. 1992;19:846–850.
    1. Waylonis GW, Heck W. Fibromyalgia syndrome. New associations. Am J Phys Med Rehabil. 1992;71:343–348.
    1. Kaplan KH, Goldenberg DL, Galvin-Nadeau M. The impact of a meditation-based stress reduction program on fibromyalgia. Gen Hosp Psychiatry. 1993;15:284–289.
    1. Neumann L, Buskila D. Epidemiology of fibromyalgia. Curr Pain Headache Rep. 2003;7:362–368.
    1. White KP, Speechley M, Harth M, Ostbye T. The London Fibromyalgia Epidemiology Study: the prevalence of fibromyalgia syndrome in London, Ontario. J Rheumatol. 1999;26:1570–1576.
    1. Geenen R, Jacobs JW. Fibromyalgia: diagnosis, pathogenesis, and treatment. Curr Opin Anaesthesiol. 2001;14:533–539.
    1. Wassem R, McDonald M, Racine J. Fibromyalgia: patient perspectives on symptoms, symptom management, and provider utilization. Clin Nurse Spec. 2002;16:24–8; discussion 29–30.
    1. Robinson RL, Birnbaum HG, Morley MA, Sisitsky T, Greenberg PE, et al. Economic cost and epidemiological characteristics of patients with fibromyalgia claims. J Rheumatol. 2003;30:1318–1325.
    1. Petzke F, Clauw DJ. Sympathetic nervous system function in fibromyalgia. Curr Rheumatol Rep. 2000;2:116–123.
    1. Kosek E, Ekholm J, Hansson P. Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms. Pain. 1996;68:375–383.
    1. Lautenbacher S, Rollman GB. Possible deficiencies of pain modulation in fibromyalgia. Clin J Pain. 1997;13:189–196.
    1. Laughlin TM, Larson AA, Wilcox GL. Mechanisms of induction of persistent nociception by dynorphin. J Pharmacol Exp Ther. 2001;299:6–11.
    1. Ignelzi RJ, Atkinson JH. Pain and its modulation. Part 2. efferent mechanisms. Neurosurgery. 1980;6:584–590.
    1. Vaeroy H, Helle R, Førre O, Kåss E, Terenius L. Cerebrospinal fluid levels of beta-endorphin in patients with fibromyalgia (fibrositis syndrome). J Rheumatol. 1988;15:1804–1806.
    1. Yunus MB, Denko CW, Masi AT. Serum beta-endorphin in primary fibromyalgia syndrome: a controlled study. J Rheumatol. 1986;13:183–186.
    1. Hamaty D, Valentine JL, Howard R, Howard CW, Wakefield V, et al. The plasma endorphin, prostaglandin and catecholamine profile of patients with fibrositis treated with cyclobenzaprine and placebo: a 5-month study. J Rheumatol. 1989;(Suppl 19):164–168.
    1. Panerai AE, Vecchiet J, Panzeri P, Meroni P, Scarone S, et al. Peripheral blood mononuclear cell beta-endorphin concentration is decreased in chronic fatigue syndrome and fibromyalgia but not in depression: preliminary report. Clin J Pain. 2002;18:270–273.
    1. Harris RE, Clauw DJ, Scott DJ, McLean SA, Gracely RH, et al. Decreased central mu-opioid receptor availability in fibromyalgia. J Neurosci. 2007;12:10000–10006.
    1. Bengtsson M, Bengtsson A, Jorfeldt L. Diagnostic epidural opioid blockade in primary fibromyalgia at rest and during exercise. Pain. 1989;39:171–180.
    1. Guieu R, Serratrice G, Pouget J. Counter irritation test in primary fibromyalgia. Clin Rheumatol. 1994;13:605–610.
    1. Price DD, Staud R, Robinson ME, Mauderli AP, Cannon R, et al. Enhanced temporal summation of second pain and its central modulation in fibromyalgia patients. Pain. 2002;99:49–59.
    1. Julien N, Goffaux P, Arsenault P, Marchand S. Widespread pain in fibromyalgia is related to a deficit of endogenous pain inhibition. Pain. 2005;114:295–302.
    1. Burckhardt CS, Clark SR, Bennett RM. The fibromyalgia impact questionnaire: development and validation. J Rheumatol. 1991;18:728–733.
    1. Bennett R. The Fibromyalgia Impact Questionnaire (FIQ): a review of its development, current version, operating characteristics and uses. Clin Exp Rheumatol. 2005;23:S154–62.
    1. Kruesi ME, Borckardt JJ, Younger JW, Nash MR, Shaw D. Pereceived links between physical problems and stress may be clouded by dissociative processes. J Trauma Dissociation. 2004;5:121–127.
    1. Derogatis LR, Lazarus L. Scl-90r, brief symptom inventory, and matching clinical rating scales. In: Maruish ME, editor. The use of psychological testing for treatment planning and outcome assessment. Hillsdale, NJ: Lawrence Erlaum; 1994. pp. 217–248.
    1. Benham G. The sensory sensitivity scale; sex and population differences April 2004
    1. Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990;33:160–172.
    1. Rollman GB, Lautenbacher S. Sex differences in musculoskeletal pain. Clin J Pain. 2001;17:20–24.
    1. Geisser ME, Gracely RH, Giesecke T, Petzke FW, Williams DA, et al. The association between experimental and clinical pain measures among persons with fibromyalgia and chronic fatigue syndrome. Eur J Pain. 2007;11:202–207.
    1. Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, et al. Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse. 1987;13:293–308.
    1. Watson D, Clark LA, Tellegen A. Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol. 1988;54:1063–1070.
    1. Crawford JR, Henry JD. The positive and negative affect schedule (PANAS): construct validity, measurement properties and normative data in a large non-clinical sample. Br J Clin Psychol. 2004;43:245–265.
    1. Malcolm R, O'Neil PM, Von JM, Dickerson PC. Naltrexone and dysphoria: a double-blind placebo controlled trial. Biol Psychiatry. 1987;22:710–716.
    1. Preston KL, Bigelow GE. Differential naltrexone antagonism of hydromorphone and pentazocine effects in human volunteers. J Pharmacol Exp Ther. 1993;264:813–823.
    1. Meyer MC, Straughn AB, Lo MW, Schary WL, Whitney CC. Bioequivalence, dose-proportionality, and pharmacokinetics of naltrexone after oral administration. J Clin Psychiatry. 1984;45:15–19.
    1. Ferrari A, Bertolotti M, Dell'Utri A, Avico U, Sternieri E. Serum time course of naltrexone and 6 beta-naltrexol levels during long-term treatment in drug addicts. Drug Alcohol Depend. 1998;52:211–220.
    1. Sax DS, Kornetsky C, Kim A. Lack of hepatotoxicity with naltrexone treatment. J Clin Pharmacol. 1994;34:898–901.
    1. Martin WR, Jasinski DR, Mansky PA. Naltrexone, an antagonist for the treatment of heroin dependence. Effects in man. Arch Gen Psychiatry. 1973;28:784–791.
    1. Cook DB, O'Connor PJ, Ray CA. Muscle pain perception and sympathetic nerve activity to exercise during opioid modulation. Am J Physiol Regul Integr Comp Physiol. 2000;279:R1565–73.
    1. Hudson JI, Hudson MS, Pliner LF, Goldenberg DL, Pope HGJ. Fibromyalgia and major affective disorder: a controlled phenomenology and family history study. Am J Psychiatry. 1985;142:441–446.
    1. Walker EA, Keegan D, Gardner G, Sullivan M, Katon WJ, et al. Psychosocial factors in fibromyalgia compared with rheumatoid arthritis: I. Psychiatric diagnoses and functional disability. Psychosom Med. 1997;59:565–571.
    1. Park DC, Glass JM, Minear M, Crofford LJ. Cognitive function in fibromyalgia patients. Arthritis Rheum. 2001;44:2125–2133.
    1. Shaver JLF, Wilbur J, Robinson FP, Wang E, Buntin MS. Women's health issues with fibromyalgia syndrome. J Womens Health (Larchmt) 2006;15:1035–1045.
    1. Aaron LA, Buchwald D. Chronic diffuse musculoskeletal pain, fibromyalgia and co-morbid unexplained clinical conditions. Best Pract Res Clin Rheumatol. 2003;17:563–574.
    1. Slotkoff AT, Radulovic DA, Clauw DJ. The relationship between fibromyalgia and the multiple chemical sensitivity syndrome. Scand J Rheumatol. 1997;26:364–367.
    1. Bell IR, Baldwin CM, Russek LG, Schwartz GE, Hardin EE. Early life stress, negative paternal relationships, and chemical intolerance in middle-aged women: support for a neural sensitization model. J Womens Health. 1998;7:1135–1147.
    1. Geisser ME, Strader Donnell C, Petzke F, Gracely RH, Clauw DJ, et al. Comorbid somatic symptoms and functional status in patients with fibromyalgia and chronic fatigue syndrome: sensory amplification as a common mechanism. Psychosomatics. 2008;49:235–242.
    1. Younger JW, Lawler-Row KA, Moe KA, Kratz AL, Keenum AJ. Effects of naltrexone on repressive coping and disclosure of emotional material: a test of the opioid-peptide hypothesis of repression and hypertension. Psychosom Med. 2006;68:734–741.
    1. King AC, Volpicelli JR, Gunduz M, O'Brien CP, Kreek MJ. Naltrexone biotransformation and incidence of subjective side effects: a preliminary study. Alcohol Clin Exp Res. 1997;21:906–909.
    1. McCaul ME, Wand GS, Rohde C, Lee SM. Serum 6-beta-naltrexol levels are related to alcohol responses in heavy drinkers. Alcohol Clin Exp Res. 2000;24:1385–1391.
    1. Riley JL3, Robinson ME, Wise EA, Price DD. A meta-analytic review of pain perception across the menstrual cycle. Pain. 1999;81:225–235.
    1. Lee MC, Wagner HNJ, Tanada S, Frost JJ, Bice AN, et al. Duration of occupancy of opiate receptors by naltrexone. J Nucl Med. 1988;29:1207–1211.
    1. Walsh SL, Sullivan JT, Preston KL, Garner JE, Bigelow GE. Effects of naltrexone on response to intravenous cocaine, hydromorphone and their combination in humans. J Pharmacol Exp Ther. 1996;279:524–538.
    1. Schuh KJ, Walsh SL, Stitzer ML. Onset, magnitude and duration of opioid blockade produced by buprenorphine and naltrexone in humans. Psychopharmacology (Berl) 1999;145:162–174.
    1. Baraniuk JN, Whalen G, Cunningham J, Clauw DJ. Cerebrospinal fluid levels of opioid peptides in fibromyalgia and chronic low back pain. BMC Musculoskelet Disord. 2004;5:48.
    1. Anderberg UM, Liu Z, Berglund L, Nyberg F. Plasma levels on nociceptin in female fibromyalgia syndrome patients. Z Rheumatol. 1998;57(Suppl 2):77–80.
    1. Giovengo SL, Russell IJ, Larson AA. Increased concentrations of nerve growth factor in cerebrospinal fluid of patients with fibromyalgia. J Rheumatol. 1999;26:1564–1569.
    1. Vaerøy H, Sakurada T, Førre O, Kåss E, Terenius L. Modulation of pain in fibromyalgia (fibrositis syndrome): cerebrospinal fluid (CSF) investigation of pain related neuropeptides with special reference to calcitonin gene related peptide (CGRP). J Rheumatol. 1989;(Suppl 19):94–97.
    1. Vaerøy H, Nyberg F, Terenius L. No evidence for endorphin deficiency in fibromyalgia following investigation of cerebrospinal fluid (CSF) dynorphin A and Met-enkephalin-Arg6-Phe7. Pain. 1991;46:139–143.

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