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Women With Dysmenorrhea Are Hypersensitive to Experimental Deep Muscle Pain Across the Menstrual Cycle

  • Stella Iacovides
    Correspondence
    Address reprint requests to Stella Iacovides, BSc (Hons), MSc, School of Physiology, University of Witwatersrand, 7 York Rd, Parktown, 2193, Johannesburg, South Africa.
    Affiliations
    Wits Dial-a-bed Sleep Laboratory, Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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  • Fiona C. Baker
    Affiliations
    Wits Dial-a-bed Sleep Laboratory, Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Human Sleep Research Program, SRI International, San Francisco, California
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  • Ingrid Avidon
    Affiliations
    Exercise Physiology Laboratory, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
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  • Alison Bentley
    Affiliations
    Wits Dial-a-bed Sleep Laboratory, Brain Function Research Group, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa

    Department of Internal Medicine, University of the Witwatersrand, Johannesburg, South Africa
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      Abstract

      Primary dysmenorrhea is a common painful condition in women that recurs every month across the reproductive years. The recurrent nociceptive input into the central nervous system that occurs during menstruation each month in women with dysmenorrhea is hypothesized to lead to increased sensitivity to painful stimuli. We investigated whether women with primary dysmenorrhea are hyperalgesic to deep muscle pain induced by a cleanly nociceptive method of hypertonic saline injection. Pain stimulation was applied both within an area of referred menstrual pain (lower back) and at a remote site outside of referred menstrual pain (forearm) in 12 healthy women with severe dysmenorrhea and 9 healthy women without dysmenorrhea, at 3 phases of the menstrual cycle: menstruation and follicular and luteal phases. Women rated their pain severity on a 100-mm visual analog scale every 30 seconds after injection until the pain subsided. In both groups of women, menstrual cycle phase had no effect on the reported intensity and duration of muscle pain. However, women with dysmenorrhea had increased sensitivity to experimental muscle pain both at the site of referred pain and at a remote nonpainful site, as assessed by peak pain severity visual analog scale rating, area under the visual analog scale curve, and pain duration, compared to women without dysmenorrhea. These data show that women with severe primary dysmenorrhea, who experience monthly menstrual pain, are hyperalgesic to deep muscle pain compared to women without dysmenorrhea.

      Perspective

      Our findings that dysmenorrheic women are hyperalgesic to a clinically relevant, deep muscle pain in areas within and outside of referred menstrual pain indicates lasting changes in pain sensitivity outside of the painful period during menstruation.

      Key words

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      References

        • Aberger E.W.
        • Denney D.R.
        • Hutchings D.F.
        Pain sensitivity and coping strategies among dysmenorrheic women: Much ado about nothing.
        Behav Res Ther. 1983; 21: 119-127
        • ACOG
        ACOG Practice Bulletin No. 51. Chronic pelvic pain.
        Obstet Gynecol. 2004; 103: 589-605
        • Amodei N.
        • Nelson-Gray R.O.
        Reactions of dysmenorrheic and nondysmenorrheic women to experimentally induced pain throughout the menstrual cycle.
        J Behav Med. 1989; 12: 373-385
        • Apkarian A.V.
        • Bushnell M.C.
        • Treede R.D.
        • Zubieta J.K.
        Human brain mechanisms of pain perception and regulation in health and disease.
        Eur J Pain. 2005; 9: 463-484
        • Arendt-Nielsen L.
        • Graven-Nielsen T.
        Muscle pain: Sensory implications and interaction with motor control.
        Clin J Pain. 2008; 24: 291-298
        • Arendt-Nielsen L.
        • Graven-Nielsen T.
        • Svarrer H.
        • Svensson P.
        The influence of low back pain on muscle activity and coordination during gait: A clinical and experimental study.
        Pain. 1996; 64: 231-240
        • As-Sanie S.
        • Harris R.E.
        • Napadow V.
        • Kim J.
        • Neshewat G.
        • Kairys A.
        • Williams D.
        • Clauw D.J.
        • Schmidt-Wilcke T.
        Changes in regional gray matter volume in women with chronic pelvic pain: A voxel-based morphometry study.
        Pain. 2012; 153: 1006-1014
        • Bajaj P.
        • Madsen H.
        • Arendt-Nielsen L.
        A comparison of modality-specific somatosensory changes during menstruation in dysmenorrheic and nondysmenorrheic women.
        Clin J Pain. 2002; 18: 180-190
        • Blankstein U.
        • Chen J.
        • Diamant N.E.
        • Davis K.D.
        Altered brain structure in irritable bowel syndrome: Potential contributions of pre-existing and disease-driven factors.
        Gastroenterology. 2010; 138: 1783-1789
        • Brinkert W.
        • Dimcevski G.
        • Arendt-Nielsen L.
        • Drewes A.M.
        • Wilder-Smith O.H.
        Dysmenorrhoea is associated with hypersensitivity in the sigmoid colon and rectum.
        Pain. 2007; 132: S46-S51
        • Coco A.S.
        Primary dysmenorrhea.
        Am Fam Physician. 1999; 60: 489-496
        • Collins S.L.
        • Moore R.A.
        • McQuay H.J.
        The visual analogue pain intensity scale: What is moderate pain in millimetres?.
        Pain. 1997; 72: 95-97
        • Craft R.M.
        • Mogil J.S.
        • Aloisi A.M.
        Sex differences in pain and analgesia: The role of gonadal hormones.
        Eur J Pain. 2004; 8: 397-411
        • Davis K.D.
        • Pope G.
        • Chen J.
        • Kwan C.L.
        • Crawley A.P.
        • Diamant N.E.
        Cortical thinning in IBS: Implications for homeostatic, attention, and pain processing.
        Neurology. 2008; 70: 153-154
        • de Leeuw R.
        • Albuquerque R.J.
        • Andersen A.H.
        • Carlson C.R.
        Influence of estrogen on brain activation during stimulation with painful heat.
        J Oral Maxillofac Surg. 2006; 64: 158-166
        • Dexter F.
        • Chestnut D.H.
        Analysis of statistical tests to compare visual analog scale measurements among groups.
        Anesthesiology. 1995; 82: 896-902
        • Drobek W.
        • Schoenaers J.
        • De Laat A.
        Hormone-dependent fluctuations of pressure pain threshold and tactile threshold of the temporalis and masseter muscle.
        J Oral Rehabil. 2002; 29: 1042-1051
        • Fillingim R.B.
        • Maixner W.
        • Girdler S.S.
        • Light K.C.
        • Harris M.B.
        • Sheps D.S.
        • Mason G.A.
        Ischemic but not thermal pain sensitivity varies across the menstrual cycle.
        Psychosom Med. 1997; 59: 512-520
        • Fillingim R.B.
        • Ness T.J.
        Sex-related hormonal influences on pain and analgesic responses.
        Neurosci Biobehav Rev. 2000; 24: 485-501
        • Freeman E.W.
        • DeRubeis R.J.
        • Rickels K.
        Reliability and validity of a daily diary for premenstrual syndrome.
        Psychiatry Res. 1996; 65: 97-106
        • Giamberardino M.A.
        • Affaitati G.
        • Valente R.
        • Iezzi S.
        • Vecchiet L.
        Changes in visceral pain reactivity as a function of estrous cycle in female rats with artificial ureteral calculosis.
        Brain Res. 1997; 774: 234-238
        • Giamberardino M.A.
        • Berkley K.J.
        • Iezzi S.
        • de Bigontina P.
        • Vecchiet L.
        Pain threshold variations in somatic wall tissues as a function of menstrual cycle, segmental site and tissue depth in non-dysmenorrheic women, dysmenorrheic women and men.
        Pain. 1997; 71: 187-197
        • Giamberardino M.A.
        • Valente R.
        • Vecchiet L.
        Muscular hyperalgesia of renal/ureteral origin.
        in: New Trends in Referred Pain and Hyperalgesia, Pain Res Clin Man. Vol. 7. Elsevier, Amsterdam1993: 149-160
        • Goldberg D.P.
        • Rickels K.
        • Downing R.
        • Hesbacher P.
        A comparison of two psychiatric screening tests.
        Br J Psychiatry. 1976; 129: 61-67
        • Goolkasian P.
        Cyclic changes in pain perception: An ROC analysis.
        Percept Psychophys. 1980; 27: 499-504
        • Goolkasian P.
        An ROC analysis of pain reactions in dysmenorrheic and nondysmenorrheic women.
        Percept Psychophys. 1983; 34: 381-386
        • Gracely R.H.
        Methods of testing pain mechanisms in normal man.
        in: Wall P.D. Melzack R. Textbook of Pain. Elsevier, London1990 (pp 315–336)
        • Granot M.
        • Yarnitsky D.
        • Itskovitz-Eldor J.
        • Granovsky Y.
        • Peer E.
        • Zimmer E.Z.
        Pain perception in women with dysmenorrhea.
        Obstet Gynecol. 2001; 98: 407-411
        • Graven-Nielsen T.
        • Arendt-Nielsen L.
        • Svensson P.
        • Jensen T.S.
        Experimental muscle pain: A quantitative study of local and referred pain in humans following injection of hypertonic saline.
        J Musculoskelet Pain. 1997; 5: 49-69
        • Graven-Nielsen T.
        • McArdle A.
        • Phoenix J.
        • Arendt-Nielsen L.
        • Jensen T.S.
        • Jackson M.J.
        • Edwards R.H.
        In vivo model of muscle pain: Quantification of intramuscular chemical, electrical, and pressure changes associated with saline-induced muscle pain in humans.
        Pain. 1997; 69: 137-143
        • Gwilym S.E.
        • Filippini N.
        • Douaud G.
        • Carr A.J.
        • Tracey I.
        Thalamic atrophy associated with painful osteoarthritis of the hip is reversible after arthroplasty: A longitudinal voxel-based morphometric study.
        Arthritis Rheum. 2010; 62: 2930-2940
        • Haman J.O.
        Pain threshold in dysmenorrhea.
        Am J Obstet Gynecol. 1944; 47: 686-691
        • Hapidou E.G.
        • De Catanzaro D.
        Sensitivity to cold pressor pain in dysmenorrheic and non-dysmenorrheic women as a function of menstrual cycle phase.
        Pain. 1988; 34: 277-283
        • Hapidou E.G.
        • Rollman G.B.
        Menstrual cycle modulation of tender points.
        Pain. 1998; 77: 151-161
        • Harlow S.D.
        • Park M.
        A longitudinal study of risk factors for the occurrence, duration and severity of menstrual cramps in a cohort of college women.
        Br J Obstet Gynaecol. 1996; 103: 1134-1142
        • Hellstrom B.
        • Lundberg U.
        Pain perception to the cold pressor test during the menstrual cycle in relation to estrogen levels and a comparison with men.
        Integr Physiol Behav Sci. 2000; 35: 132-141
        • Hermann C.
        • Zohsel K.
        • Hohmeister J.
        • Flor H.
        Cortical correlates of an attentional bias to painful and innocuous somatic stimuli in children with recurrent abdominal pain.
        Pain. 2008; 136: 397-406
        • Hodges P.W.
        • Mellor R.
        • Crossley K.
        • Bennell K.
        Pain induced by injection of hypertonic saline into the infrapatellar fat pad and effect on coordination of the quadriceps muscles.
        Arthritis Rheum. 2009; 61: 70-77
        • Isselee H.
        • De Laat A.
        • Bogaerts K.
        • Lysens R.
        Long-term fluctuations of pressure pain thresholds in healthy men, normally menstruating women and oral contraceptive users.
        Eur J Pain. 2001; 5: 27-37
        • Kellgren J.H.
        Observations on referred pain arising from muscle.
        Clin Sci. 1938; 3: 175-190
        • Klatzkin R.R.
        • Mechlin B.
        • Girdler S.S.
        Menstrual cycle phase does not influence gender differences in experimental pain sensitivity.
        Eur J Pain. 2010; 14: 77-82
        • Kowalczyk W.J.
        • Evans S.M.
        • Bisaga A.M.
        • Sullivan M.A.
        • Comer S.D.
        Sex differences and hormonal influences on response to cold pressor pain in humans.
        J Pain. 2006; 7: 151-160
        • Kowalczyk W.J.
        • Sullivan M.A.
        • Evans S.M.
        • Bisaga A.M.
        • Vosburg S.K.
        • Comer S.D.
        Sex differences and hormonal influences on response to mechanical pressure pain in humans.
        J Pain. 2010; 11: 330-342
        • Kuczmierczyk A.R.
        • Adams H.E.
        Autonomic arousal and pain sensitivity in women with premenstrual syndrome at different phases of the menstrual cycle.
        J Psychosom Res. 1986; 30: 421-428
        • Kuczmierczyk A.R.
        • Adams H.E.
        • Calhoun K.S.
        • Naor S.
        • Giombetti R.
        • Cattalani M.
        • McCann P.
        Pain responsivity in women with premenstrual syndrome across the menstrual cycle.
        Percept Mot Skills. 1986; 63: 387-393
        • Latremoliere A.
        • Woolf C.J.
        Central sensitization: A generator of pain hypersensitivity by central neural plasticity.
        J Pain. 2009; 10: 895-926
        • Lee S.J.
        • McEwen B.S.
        Neurotrophic and neuroprotective actions of estrogens and their therapeutic implications.
        Annu Rev Pharmacol Toxicol. 2001; 41: 569-591
        • Lei J.
        • You H.J.
        Variation of pain and vasomotor responses evoked by intramuscular infusion of hypertonic saline in human subjects: Influence of gender and its potential neural mechanisms.
        Brain Res Bull. 2012; 87: 564-570
        • Martin V.T.
        Ovarian hormones and pain response: A review of clinical and basic science studies.
        Gend Med. 2009; 6: 168-192
        • McNair D.M.
        • Lorr M.
        • Droppleman L.F.
        EdITS Manual for the Profile of Mood States.
        Educational and Industrial Testing Service, San Diego, CA1992
        • McRoberts J.A.
        • Li J.
        • Ennes H.S.
        • Mayer E.A.
        Sex-dependent differences in the activity and modulation of N-methyl-d-aspartic acid receptors in rat dorsal root ganglia neurons.
        Neuroscience. 2007; 148: 1015-1020
        • Olafsdottir L.B.
        • Gudjonsson H.
        • Jonsdottir H.H.
        • Bjornsson E.
        • Thjodleifsson B.
        Natural history of irritable bowel syndrome in women and dysmenorrhea: A 10-year follow-up study.
        Gastroenterol Res Pract. 2012; 2012: 534204
        • Oshima M.
        • Ogawa R.
        • Londyn D.
        Current perception threshold increases during pregnancy but does not change across menstrual cycle.
        J Nihon Med Sch. 2002; 69: 19-23
        • Pfleeger M.
        • Straneva P.A.
        • Fillingim R.B.
        • Maixner W.
        • Girdler S.S.
        Menstrual cycle, blood pressure and ischemic pain sensitivity in women: A preliminary investigation.
        Int J Psychophysiol. 1997; 27: 161-166
        • Proctor M.
        • Farquhar C.
        Dysmenorrhoea.
        Clin Evid. 2002; 7: 1639-1653
        • Rhudy J.L.
        • Bartley E.J.
        The effect of the menstrual cycle on affective modulation of pain and nociception in healthy women.
        Pain. 2010; 149: 365-372
        • Ribeiro-Dasilva M.C.
        • Shinal R.M.
        • Glover T.
        • Williams R.S.
        • Staud R.
        • Riley 3rd, J.L.
        • Fillingim R.B.
        Evaluation of menstrual cycle effects on morphine and pentazocine analgesia.
        Pain. 2011; 152: 614-622
        • Riley 3rd, J.L.
        • Robinson M.E.
        • Wise E.A.
        • Price D.D.
        A meta-analytic review of pain perception across the menstrual cycle.
        Pain. 1999; 81: 225-235
        • Robinson J.E.
        • Short R.V.
        Changes in breast sensitivity at puberty, during the menstrual cycle, and at parturition.
        Br Med J. 1977; 1: 1188-1191
        • Sherman J.J.
        • LeResche L.
        Does experimental pain response vary across the menstrual cycle? A methodological review.
        Am J Physiol Regul Integr Comp Physiol. 2006; 291: R245-R256
        • Sherman J.J.
        • LeResche L.
        • Mancl L.A.
        • Huggins K.
        • Sage J.C.
        • Dworkin S.F.
        Cyclic effects on experimental pain response in women with temporomandibular disorders.
        J Orofac Pain. 2005; 19: 133-143
        • Stening K.
        • Eriksson O.
        • Wahren L.
        • Berg G.
        • Hammar M.
        • Blomqvist A.
        Pain sensations to the cold pressor test in normally menstruating women: Comparison with men and relation to menstrual phase and serum sex steroid levels.
        Am J Physiol Regul Integr Comp Physiol. 2007; 293: R1711-R1716
        • Stohler C.S.
        • Kowalski C.J.
        Spatial and temporal summation of sensory and affective dimensions of deep somatic pain.
        Pain. 1999; 79: 165-173
        • Straneva P.A.
        • Maixner W.
        • Light K.C.
        • Pedersen C.A.
        • Costello N.L.
        • Girdler S.S.
        Menstrual cycle, beta-endorphins, and pain sensitivity in premenstrual dysphoric disorder.
        Health Psychol. 2002; 21: 358-367
        • Tang N.K.
        • Salkovskis P.M.
        • Hodges A.
        • Wright K.J.
        • Hanna M.
        • Hester J.
        Effects of mood on pain responses and pain tolerance: An experimental study in chronic back pain patients.
        Pain. 2008; 138: 392-401
        • Tassorelli C.
        • Sandrini G.
        • Cecchini A.P.
        • Nappi R.E.
        • Sances G.
        • Martignoni E.
        Changes in nociceptive flexion reflex threshold across the menstrual cycle in healthy women.
        Psychosom Med. 2002; 64: 621-626
        • Teutsch S.
        • Herken W.
        • Bingel U.
        • Schoell E.
        • May A.
        Changes in brain gray matter due to repetitive painful stimulation.
        Neuroimage. 2008; 42: 845-849
        • Tu C.H.
        • Niddam D.M.
        • Chao H.T.
        • Chen L.F.
        • Chen Y.S.
        • Wu Y.T.
        • Yeh T.C.
        • Lirng J.F.
        • Hsieh J.C.
        Brain morphological changes associated with cyclic menstrual pain.
        Pain. 2010; 150: 462-468
        • Tu C.H.
        • Niddam D.M.
        • Chao H.T.
        • Liu R.S.
        • Hwang R.J.
        • Yeh T.C.
        • Hsieh J.C.
        Abnormal cerebral metabolism during menstrual pain in primary dysmenorrhea.
        Neuroimage. 2009; 47: 28-35
        • Twyman R.E.
        • Macdonald R.L.
        Neurosteroid regulation of GABAA receptor single-channel kinetic properties of mouse spinal cord neurons in culture.
        J Physiol. 1992; 456: 215-245
        • Vecchiet L.
        • Giamberardino M.A.
        • Dragani L.
        • Galletti R.
        • Albe-Fessard D.
        Referred muscular hyperalgesia from viscera: Clinical approach.
        in: Lipton S. The Pain Clinic, Adv Pain Res Ther. Raven Press, New York1990: 175-182
        • Veith J.L.
        • Anderson J.
        • Slade S.A.
        • Thompson P.
        • Laugel G.R.
        • Getzlaf S.
        Plasma beta-endorphin, pain thresholds and anxiety levels across the human menstrual cycle.
        Physiol Behav. 1984; 32: 31-34
        • Villemure C.
        • Bushnell M.C.
        Cognitive modulation of pain: How do attention and emotion influence pain processing?.
        Pain. 2002; 95: 195-199
        • Vincent K.
        • Warnaby C.
        • Stagg C.J.
        • Moore J.
        • Kennedy S.
        • Tracey I.
        Dysmenorrhoea is associated with central changes in otherwise healthy women.
        Pain. 2011; 152: 1966-1975
        • Woolf C.J.
        Central sensitization: Implications for the diagnosis and treatment of pain.
        Pain. 2011; 152: S2-15
        • Yunus M.B.
        Fibromyalgia and overlapping disorders: The unifying concept of central sensitivity syndromes.
        Semin Arthritis Rheum. 2007; 36: 339-356
        • Zondervan K.T.
        • Yudkin P.L.
        • Vessey M.P.
        • Jenkinson C.P.
        • Dawes M.G.
        • Barlow D.H.
        • Kennedy S.H.
        Chronic pelvic pain in the community—Symptoms, investigations, and diagnoses.
        Am J Obstet Gynecol. 2001; 184: 1149-1155