Abstract
Fibromyalgia syndrome (FMS) is a prevalent musculoskeletal pain disorder characterized by diffuse pain and associated psychophysiological symptoms. Despite extensive research in the past 3 decades, the etiology and pathophysiology of FMS and effective treatment approaches are yet to be delineated. Recently, it has been suggested that FMS may be related to hypofunctional stress systems, particularly in the autonomic nervous system (ANS) and the hypothalamic-pituitary-adrenal (HPA) axis. Studies have demonstrated that patients with FMS exhibit lowered sympathoadrenal reactivity to stress. These findings seem to be consistent with the large volume of research indicating the inverse relationship between pain sensitivity and sympathetic reactivity. In this paper, we discuss the role of stress in the pain experience in general, stress in patients with FMS, and review the studies evaluating the ANS and HPA functions in response to various stressors.
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REFERENCES
Ahles, T. A., Khan, S. A., Yunus, M. B., Spiegel, D. A., & Masi, A. T. (1991). Psychiatric status of patients with primary fibromyalgia, patients with rheumatoid arthritis, and subjects without pain: A blind comparison of DSM-III diagnoses. American Journal of Psychiatry, 148, 1721–1726.
Aicher, S., & Randich, A. (1990). Antinociception and cardiovascular responses produced by electrical stimulation in the nucleus tractus solitarius, nucleus reticularis ventralis, and the caudal medulla. Pain, 42, 103–119.
Alfici, S., Sigal, M., & Landau, M. (1989). Primary fibromyalgia syndrome―a variant of depressive disorder? Psychotherapy and Psychosomatics, 51, 156–161.
Angrilli, A., Mini, A., Mucha, R. F., & Rau, H. (1997). The influence of low blood pressure and baroreceptor activity on pain responses. Physiology and Behavior, 62, 391–397.
Benarroch, E. (1997). Central autonomic network: Functional organization and clinical correlations. New York: Futura.
Bengtsson, A., & Bengtsson, M. (1988). Regional sympathetic blockade in primary fibromyalgia. Pain, 33, 161–167.
Bennett, R. M., Clark, S. R., Campbell, S. M., & Burckhardt, C. S. (1992). Lowlevels of somatomedin C in patients with the fibromyalgia syndrome. A possible link between sleep and muscle pain. Arthritis and Rheumatism, 35, 1113–1116.
Bennett, R. M., Clark, S. R., Campbell, S. M., Ingram, S. B., Burckhardt, C. S., Nelson, D. L., et al. (1991). Symptoms of Raynaud's syndrome in patients with fibromyalgia. A study utilizing the Nielsen test, digital photoplethysmography, and measurements of platelet alpha 2-adrenergic receptors. Arthritis and Rheumatism, 34, 264–269.
Bennett, R. M., Clark, S. R., Goldberg, L., Nelson, D., Bonafede, R. P., Porter, J., et al. (1989). Aerobic fitness in patients with fibrositis. A controlled study of respiratory gas exchange and 133xenon clearance from exercising muscle. Arthritis and Rheumatism, 32, 454–460.
Bombardier, C. H., & Buchwald, D. (1996). Chronic fatigue, chronic fatigue syndrome, and fibromyalgia. Disability and health-care use. Medical Care, 34, 924–930.
Bou-Holaigah, I., Calkins, H., Flynn, J. A., Tunin, C., Chang, H. C., Kan, J. S., et al. (1997). Provocation of hypotension and pain during upright tilt table testing in adults with fibromyalgia. Clinical and Experimental Rheumatology, 15, 239–246.
Brody, S., Angrilli, A., Weiss, U., Birbaumer, N., Mini, A., Veit, R., et al. (1997). Somatotosensory evoked potentials during baroreceptor stimulation in chronic low back pain patients and normal controls. International Journal of Psychophysiology, 25, 201–210.
Buckhardt, C., Clark, S., & Nelson, D. (1988). Assessing physical fitness of women with rheumatic disease. Arthritis Care and Research, 1, 38–44.
Bullinger, M., Naber, D., Pickar, D., Cohen, R. M., Kalin, N. H., Pert, A., et al. (1984). Endocrine effects of the cold pressor test: Relationships to subjective pain appraisal and coping. Psychiatry Research, 12, 227–233.
Burckhardt, C. S., Clark, S. R., & Bennett, R. M. (1993). Fibromyalgia and quality of life: A comparative analysis. Journal of Rheumatology, 20, 475–479.
Burnett, A., & Gebhart, G. (1991). Characterization of descending modulation of nociception from the A5 cell group. Brain Research, 546, 271–281.
Caceres, C., & Burns, J. W. (1997). Cardiovascular reactivity to psychological stress may enhance subsequent pain sensitivity. Pain, 69, 237–244.
Celiker, R., Borman, P., Oktem, F., Gokce-Kutsal, Y., & Basgoze, O. (1997). Psychological disturbance in fi-bromyalgia: Relation to pain severity. Clinical Rheumatology, 16, 179–184.
Chapman, C. R., Oka, S., Bradshaw, D. H., Jacobson, R. C., & Donaldson, G. W. (1999). Phasic pupil dilation response to noxious stimulation in normal volunteers: Relationship to brain evoked potentials and pain report. Psychophysiology, 36, 44–52.
Clauw, D. J. (1995). The pathogenesis of chronic pain and fatigue syndromes, with special reference to fibromyalgia. Medical Hypotheses, 44, 369–378.
Clauw, D. J., & Chrousos, G. P. (1997). Chronic pain and fatigue syndromes: Overlapping clinical and neuroendocrine features and potential pathogenic mechanisms. Neuroimmunomodulation, 4, 134–153.
Crofford, L. J., Pillemer, S. R., Kalogeras, K. T., Cash, J. M., Michelson, D., Kling, M. A., et al. (1994). Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia. Arthritis and Rheumatism, 37, 1583–1592.
Dinerman, H., Goldenberg, D. L., & Felson, D. T. (1986). A prospective evaluation of 118 patients with the fibromyalgia syndrome: Prevalence of Raynaud's phenomenon, sicca symptoms, ANA, low complement, and Ig deposition at the dermal—epidermal junction. Journal of Rheumatology, 13, 368–373.
Droste, C., Kardos, A., Brody, S., Greenlee, M. W., Roskamm, H., & Rau, H. (1994). Baroreceptor stimulation: Pain perception and sensory thresholds. Biological Psychology, 37(2), 101–113.
Durette, M. R., Rodriquez, A. A., Agre, J. C., & Silverman, J. L. (1991). Needle electromyographic evaluation of patients with myofascial or fibromyalgic pain. American Journal of Physical Medicine and Rehabilitation, 70, 154–156.
Dworkin, B., Elbert, T., Rau, H., Birbaumer, N., Pauli, P., Droste, C., et al. (1994). Central effects of baroreceptor activation in humans: Attenuation of skeletal reflexes and pain perception. Proceedings of The National Academy of Sciences of The United States of America, 91, 6329–6333.
Dworkin, B., Filewich, R., Miller, N., Craigmyle, N., & Pickering, T. (1979). Baroreceptor activation reduces reactivity to noxious stimulation: Implications for hypertension. Science, 205, 1299–1301.
Edelson, J. T., & Robertson, G. L. (1986). The effect of the cold pressor test on vasopressin secretion in man. Psychoneuroendocrinology, 11, 307–316.
Elam, M., Johansson, G., & Wallin, B. G. (1992). Do patients with primary fibromyalgia have an altered muscle sympathetic nerve activity? Pain, 48, 371–375.
Ellermeier, W., & Westphal, W. (1995). Gender differences in pain ratings and pupil reactions to painful pressure stimuli. Pain, 61, 435–439.
Falcone, C., Auguadro, C., Sconocchia, R., & Angoli, L. (1997). Susceptibility to pain in hypertensive and normotensive patients with coronary artery disease: Response to dental pulp stimulation. Hypertensionv, 30, 1279–1283.
Flor, H., Birbaumer, N., Schugens, M. M., & Lutzenberger, W. (1992). Symptom-specific psychophysiological responses in chronic pain patients. Psychophysiology, 29, 452–460.
Flor, H., & Turk, D. C. (1989). Psychophysiology of chronic pain: Do chronic pain patients exhibit symptom specific psychophysiological responses? Psychological Bulletin, 105, 215–259.
Forseth, K. O., Gran, J. T., & Husby, G. (1997). A population study of the incidence of fibromyalgia among women aged 26-55 yr. British Journal of Rheumatology, 36, 1318–1323.
Ghione, S., Rosa, C., Mezzasalma, L., & Panattoni, E. (1988). Arterial hypertension is associated with hypalgesia in humans. Hypertension, 12, 491–497.
Go, B. M., Sheffield, D., Krittayaphong, R., Maixner, W., & Sheps, D. S. (1997). Association of systolic blood pressure at time of myocardial ischemia with angina pectoris during exercise testing. American Journal of Cardiology, 79, 954–956.
Griep, E. N., Boersma, J. W., & de Kloet, E. R. (1993). Altered reactivity of the hypothalamic-pituitary-adrenal axis in the primary fibromyalgia syndrome. Journal of Rheumatology, 2, 469–474.
Griep, E. N., Boersma, J. W., & de Kloet, E. R. (1994). Pituitary release of growth hormone and prolactin in the primary fibromyalgia syndrome. Journal of Rheumatology, 21, 2125–2130.
Guasti, L., Cattaneo, R., Rinaldi, O., Rossi, M. G., Bianchi, L., Gaudio, G., et al. (1995). Twenty-four-hour noninvasive blood pressure monitoring and pain perception. Hypertension, 25, 1301–1305.
Hrycaj, P., Stratz, T., & Muller, W. (1993). Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. Journal of Rheumatology, 20, 1986–1988.
Jacobsen, S., & Holm, B. (1992). Muscle strength and endurance compared to aerobic capacity in primary fibromyalgia syndrome. Clinical and Experimental Rheumatology, 10, 419–420.
Jones, S. (1991). Descending noradrenergic influences on pain. Progress in Brain Research, 88, 381–394.
Kelemen, J., Lang, E., Balint, G., Trocsanyi, M., & Muller, W. (1998). Orthostatic sympathetic derangement of baroreflex in patients with fibromyalgia. Journal of Rheumatology, 25, 823–825.
Kelly, D. (Ed.). (1986). Stress-induced analgesia. New York: New York Academy of Sciences.
Kosek, E., Ekholm, J., & Hansson, P. (1996). Sensory dysfunction in fibromyalgia patients with implications for pathogenic mechanisms. Pain, 68, 375–383.
Kosek, E., & Hansson, P. (1997). Modulatory influence on somatosensory perception from vibration and heterotopic noxious conditioning stimulation (HNCS) in fibromyalgia patients and healthy subjects. Pain, 70, 41–51.
Krag, N. J., Norregaard, J., Larsen, J. K., & Danneskiold-Samsoe, B. (1994). A blinded, controlled evaluation of anxiety and depressive symptoms in patients with fibromyalgia, as measured by standardized psychometric interview scales. Acta Psychiatrica Scandinavica, 89, 370–375.
Lariviere, W. R., & Melzack, R. (2000). The role of corticotropin-releasing factor in pain and analgesia. Pain, 84, 1–12.
Lindh, M., Johansson, G., Hedberg, M., Henning, G. B., & Grimby, G. (1995). Muscle fiber characteristics, capillaries and enzymes in patients with fibromyalgia and controls. Scandinavian Journal of Rheumatology, 24, 34–37.
Low, P. A., Opfer-Gehrking, T. L., McPhee, B. R., Fealey, R. D., Benarroch, E. E., Willner, C. L., et al. (1995). Prospective evaluation of clinical characteristics of orthostatic hypotension. Mayo Clinic Proceedings, 70, 617–622.
Maixner, W., Touw, K., Brody, M., Gebhart, G., & Long, J. (1992). Factors influencing the altered pain perception in the spontaneously hypertensive rat. Brain Research, 237, 137–145.
McDermid, A. J., Rollman, G. B., & McCain, G. A. (1996). Generalized hypervigilance in fibromyalgia: Evidence of perceptual amplification. Pain, 66, 133–144.
Miller, J., & Proudfit, H. (1990). Antagonism of stimulation-produced antinociception from ventrolateral pontine sties by intrathecal administration of a-adrenergic antagonists and naloxone. Brain Research, 530, 20–34.
Moldofsky, H., & Scarisbrick, P. (1976). Induction of neurasthenic musculoskeletal pain syndrome by selective sleep stage deprivation. Psychosomatic Medicine, 38, 35–44.
Moldofsky, H., Scarisbrick, P., England, R., & Smythe, H. (1975). Musculosketal symptoms and non-REM sleep disturbance in patients with “fibrositis syndrome” and healthy subjects. Psychosomatic Medicine, 37, 341–351.
Morris, V., Cruwys, S., & Kidd, B. (1998). Increased capsaicin-induced secondary hyperalgesia as a marker of abnormal sensory activity in patients with fibromyalgia. Neuroscience Letters, 250, 205–207.
Mountz, J. M., Bradley, L. A., Modell, J. G., Alexander, R.W., Triana-Alexander, M., Aaron, L. A., et al. (1995). Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis and Rheumatism, 38, 926–938.
Myers, J. K., Weissman, M. M., Tischler, G. L., Holzer, C. E. D., Leaf, P. J., Orvaschel, H., et al. (1984). Six-month prevalence of psychiatric disorders in three communities 1980 to 1982. Archives of Genearl Psychiatry, 41, 959–967.
Norregaard, J., Bulow, P. M., & Danneskiold-Samsoe, B. (1994). Muscle strength, voluntary activation, twitch properties, and endurance in patients with fibromyalgia. Journal of Neurology, Neurosurgery, and Psychiatry, 57, 1106–1111.
Okifuji, A., & Turk, D. (1999). Fibromyalgia: Search for mechanisms and effective treatments. In R. Gatchel & D. Turk (Eds.), Psychological factors in pain: Evolution and revolution (pp. 227–246). New York: Guilford.
Okifuji, A., Turk, D. C., & Marcus, D. A. (1999). Comparison of generalized and localized hyperalgesia in recurrent headache and fibromyalgia patients. Psychosomatic Medicine, 61, 771–778.
Okifuji, A., Turk, D. C., Sinclair, J. D., Starz, T.W., & Marcus, D. A. (1997). A standardized manual tender point survey. I. Development and determination of a threshold point for the identification of positive tender points in fibromyalgia syndrome. Journal of Rheumatology, 24, 377–383.
Page, G. D., & France, C. R. (1997). Objective evidence of decreased pain perception in normotensives at risk for hypertension. Pain, 73, 173–180.
Peckerman, A., Hurwitz, B. E., Saab, P. G., Llabre, M. M., McCabe, P. M., & Schneiderman, N. (1994). Stimulus dimensions of the cold pressor test and the associated patterns of cardiovascular response. Psychophysiology, 31, 282–290.
Pillemer, S. R., Bradley, L. A., Crofford, L. J., Moldofsky, H., & Chrousos, G. P. (1997). The neuroscience and endocrinology of fibromyalgia. Arthritis and Rheumatism, 40, 1928–1939.
Qiao, Z. G., Vaeroy, H., & Morkrid, L. (1991). Electrodermal and microcirculatory activity in patients with fibromyalgia during baseline, acoustic stimulation and cold pressor tests. Journal of Rheumatology, 18, 1383–1389.
Randich, A., Ren, K., & Gebhart, G. F. (1990). Electrical stimulation of cervical vagal afferents. II. Central relays for behavioral antinociception and arterial blood pressure decreases. Journal of Neurophysiology, 64, 1115–1124.
Rollman, G., & Lautenbacher, S. (1993). Hypervigiliance effects in fibromyalgia: Pain experience and perception. In H. Vaeroy & H. Merskey (Eds.), Progress in fibromyalgia and myofascial pain. Amsterdam: Elsevier.
Rosa, C., Vignocchi, G., Panattoni, E., Rossi, B., & Ghione, S. (1994). Relationship between increased blood pressure and hypoalgesia: Additional evidence for the existence of an abnormality of pain perception in arterial hypertension in humans. Journal of Human Hypertension, 8, 119–126.
Russell, I. J., Michalek, J. E., Vipraio, G. A., Fletcher, E. M., Javors, M. A., & Bowden, C. A. (1992). Platelet 3H-imipramine uptake receptor density and serum serotonin levels in patients with fibromyalgia/fibrositis syndrome. Journal of Rheumatology, 19, 104–109.
Russell, I. J., Orr, M. D., Littman, B., Vipraio, G. A., Alboukrek, D., Michalek, J. E., et al. (1994). Elevated cerebrospinal fluid levels of substance P in patients with the fibromyalgia syndrome. Arthritis and Rheumatism, 37, 1593–1601.
Sheps, D. S., Ballenger, M. N., De Gent, G. E., Krittayaphong, R., Dittman, E., Maixner, W., et al. (1995). Psychophysical responses to a speech stressor: Correlation of plasma beta-endorphin levels at rest and after psychological stress with thermally measured pain threshold in patients with coronary artery disease. Journal of American College of Cardiology, 25, 1499–1503.
Sietsema, K. E., Cooper, D. M., Caro, X., Leibling, M. R., & Louie, J. S. (1993). Oxygen uptake during exercise in patients with primary fibromyalgia syndrome. Journal of Rheumatology, 20, 860–865.
Simms, R.W. (1996). Is there muscle pathology in fibromyalgia syndrome? Rheumatic Diseases Clinics of North America, 22, 245–266.
Sorensen, J., Graven-Nielsen, T., Henriksson, K. G., Bengtsson, M., & Arendt-Nielsen, L. (1998). Hyperexcitability in fibromyalgia. Journal of Rheumatology, 25, 152–155.
Stewart, K. M., & France, C. R. (1996). Resting systolic blood pressure, parental history of hypertension, and sensitivity to noxious stimuli. Pain, 68, 369–374.
Thompson, J. M. (1990). Tension myalgia as a diagnosis at the Mayo Clinic and its relationship to fibrositis, fibromyalgia, and myofascial pain syndrome. Mayo Clinic Proceedings, 65, 1237–1248.
Torpy, D. J., Papanicolaou, D. A., Lotsikas, A. J., Wilder, R. L., Chrousos, G. P., & Pillemer, S. R. (2000). Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6: A pilot study in fibromyalgia. Arthritis and Rheumatis, 43, 872–880.
Turk, D. C., & Flor, H. (1989). Primary fibromyalgia is greater than tender points: Toward a multiaxial taxonomy. Journal of Rheumatology, 16, 80–86.
Turk, D. C., Okifuji, A., Sinclair, J. D., & Starz, T.W. (1996). Pain, disability, and physical functioning in subgroups of patients with fibromyalgia. Journal of Rheumatology, 23, 1255–1262.
Uveges, J. M., Parker, J. C., Smarr, K. L., McGowan, J. F., Lyon, M. G., Irvin, W. S., et al. (1990). Psychological symptoms in primary fibromyalgia syndrome: Relationship to pain, life stress, and sleep disturbance. Arthritis and Rheumatism, 33, 1279–1283.
Vaeroy, H., Helle, R., Forre, O., Kass, E., & Terenius, L. (1988). Elevated CSF levels of substance P and high incidence of Raynaud phenomenon in patients with fibromyalgia: New features for diagnosis. Pain, 32, 21–26.
Vaeroy, H., Qiao, Z. G., Morkrid, L., & Forre, O. (1989). Altered sympathetic nervous system response in patients with fibromyalgia (fibrositis syndrome). Journal of Rheumatology, 16, 1460–1465.
van Denderen, J. C., Boersma, J. W., Zeinstra, P., Hollander, A. P., & van Neerbos, B. R. (1992). Physiological effects of exhaustive physical exercise in primary fibromyalgia syndrome (PFS): Is PFS a disorder of neuroendocrine reactivity? Scandinavian Journal of Rheumatology, 21, 35–37.
van Lieshout, J., Wieling, W., Karemaker, J., & Eckberg, D. (1991). The vasovagal response. Clinical Science, 81, 575–586.
Walker, E. A., Keegan, D., Gardner, G., Sullivan, M., Katon, W. J., & Bernstein, D. (1997). Psychosocial factors in fibromyalgia compared with rheumatoid arthritis: I. Psychiatric diagnoses and functional disability. Psychosomatic Medicine, 59, 565–571.
White, K. P., Speechley, M., Harth, M., & Ostbye, T. (1995). Fibromyalgia in rheumatology practice: A survey of Canadian rheumatologists. Journal of Rheumatology, 22, 722–726.
White, K. P., Speechley, M., Harth, M., & Ostbye, T. (1999). The London fibromyalgia epidemiology study: The prevalence of fibromyalgia syndrome in London, Ontario. Journal of Rheumatology, 26, 1570–1576.
Wolfe, F. (1990). Fibromyalgia. Rheumatic Diseases Clinics of North America, 16, 681–698.
Wolfe, F., Anderson, J., Harkness, D., Bennett, R. M., Caro, X. J., Goldenberg, D. L., et al. (1997). Health status and disease severity in fibromyalgia: Results of a six-center longitudinal study. Arthritis and Rheumatism, 40, 1571–1579.
Wolfe, F., Russell, I. J., Vipraio, G., Ross, K., & Anderson, J. (1997). Serotonin levels, pain threshold, and fibromyalgia symptoms in the general population. Journal of Rheumatology, 24, 555–559.
Wolfe, F., Smythe, H. A., Yunus, M. B., Bennett, R. M., Bombardier, C., Goldenberg, D. L., et al. (1990). The American College of Rheumatology 1990 criteria for the classification of fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis and Rheumatism, 33, 160–172.
Woolf, C. J., & Mannion, R. J. (1999). Neuropathic pain: Aetiology, symptoms, mechanisms, and management. Lancet, 353, 1959–1964.
Yunus, M. B. (1989). Primary fibromyalgia syndrome: A critical evaluation of recent criteria developments. Zeitschrift fur Rheumatologie, 48, 217–222.
Yunus, M. B. (1992). Towards a model of pathophysiology of fibromyalgia: Aberrant central pain mechanisms with peripheral modulation. Journal of Rheumatology, 19, 846–850.
Zidar, J., Backman, E., Bengtsson, A., & Henriksson, K. G. (1990). Quantitative EMG and muscle tension in painful muscles in fibromyalgia. Pain, 40, 249–254.
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Okifuji, A., Turk, D.C. Stress and Psychophysiological Dysregulation in Patients with Fibromyalgia Syndrome. Appl Psychophysiol Biofeedback 27, 129–141 (2002). https://doi.org/10.1023/A:1016243710507
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DOI: https://doi.org/10.1023/A:1016243710507