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The Influence of Menstrual Phases on Pain Modulation in Healthy Women

      Abstract

      This study investigated if conditioned pain modulation (CPM) varies across the menstrual cycle in healthy, normally menstruating women and investigated correlations between sex hormone levels and CPM across the menstrual cycle. Thirty-six normally menstruating women were tested during 3 phases of the menstrual cycle: early follicular, ovulatory, and midluteal, confirmed by hormone determinations. Mechanical pressure (test stimulus) was applied to the masseter muscle and the induced pain assessed before, during, and after immersion of the hand into ice water (conditioning stimulus) to activate CPM or tepid water (control). Conditioning pain, ie, pain in the hand during CPM/control experiment, and tolerance time were also measured. Test pain intensity was suppressed during CPM in all phases (P < .001), but with more effective suppression during the ovulatry than during the early follicular phase (P < .05). There were no changes in test pain intensity during the control experiment and no significant differences in conditioning pain, or tolerance time between phases. In conclusion, our results showed more effective pain modulation in the ovulatory phase of the menstrual cycle, when estradiol levels are high and progesterone levels are low, than in the early follicular phase when both these hormones are low.

      Perspective

      Deficient pain modulation is believed to be an important pathogenic factor in many chronic pain conditions that affect women. This article shows that sex hormones modulate conditioned pain modulation, because pain inhibition was more effective in the ovulatory phase of the menstrual cycle than in the early follicular phase.

      Key words

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      References

        • Amandusson A.
        • Blomqvist A.
        Estrogen receptor-alpha expression in nociceptive-responsive neurons in the medullary dorsal horn of the female rat.
        Eur J Pain. 2010; 14: 245-248
        • Bragdon E.E.
        • Light K.C.
        • Girdler S.S.
        • Maixner W.
        Blood pressure, gender, and parental hypertension are factors in baseline and poststress pain sensitivity in normotensive adults.
        Int J Behav Med. 1997; 4: 17-38
        • Brynhildsen J.O.
        • Hammar J.
        • Hammar M.L.
        Does the menstrual cycle and use of oral contraceptives influence the risk of low back pain? A prospective study among female soccer players.
        Scand J Med Sci Sports. 1997; 7: 348-353
        • Dao T.T.
        • LeResche L.
        Gender differences in pain.
        J Orofac Pain. 2000; 14: 169-184
        • Dickenson A.H.
        • Le Bars D.
        Diffuse noxious inhibitory controls (DNIC) involve trigeminothalamic and spinothalamic neurones in the rat.
        Exp Brain Res. 1983; 49: 174-180
        • Dickenson A.H.
        • Le Bars D.
        • Besson J.M.
        Diffuse noxious inhibitory controls (DNIC). Effects on trigeminal nucleus caudalis neurones in the rat.
        Brain Res. 1980; 200: 293-305
        • Edwards R.R.
        • Ness T.J.
        • Weigent D.A.
        • Fillingim R.B.
        Individual differences in diffuse noxious inhibitory controls (DNIC): Association with clinical variables.
        Pain. 2003; 106: 427-437
        • Farrar J.T.
        • Young Jr., J.P.
        • LaMoreaux L.
        • Werth J.L.
        • Poole R.M.
        Clinical importance of changes in chronic pain intensity measured on an 11-point numerical pain rating scale.
        Pain. 2001; 94: 149-158
        • Fillingim R.B.
        Sex, gender, and pain: Women and men really are different.
        Curr Rev Pain. 2000; 4: 24-30
        • 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
        • Flores C.A.
        • Shughrue P.
        • Petersen S.L.
        • Mokha S.S.
        Sex-related differences in the distribution of opioid receptor-like 1 receptor mRNA and colocalization with estrogen receptor mRNA in neurons of the spinal trigeminal nucleus caudalis in the rat.
        Neuroscience. 2003; 118: 769-778
        • Forsberg C.
        • Björvell H.
        Swedish population norms for the GHRI, HI and STAI-state.
        Qual Life Res. 1993; 2: 349-356
        • Granot M.
        • Weissman-Fogel I.
        • Crispel Y.
        • Pud D.
        • Granovsky Y.
        • Sprecher E.
        • Yarnitsky D.
        Determinants of endogenous analgesia magnitude in a diffuse noxious inhibitory control (DNIC) paradigm: Do conditioning stimulus painfulness, gender and personality variables matter?.
        Pain. 2008; 136: 142-149
        • Hapidou E.G.
        • Rollman G.B.
        Menstrual cycle modulation of tender points.
        Pain. 1998; 77: 151-161
        • Hellström B.
        • Anderberg U.M.
        Pain perception across the menstrual cycle phases in women with chronic pain.
        Percept Mot Skills. 2003; 96: 201-211
        • Hellström 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
        • Julien N.
        • Marchand S.
        Endogenous pain inhibitory systems activated by spatial summation are opioid-mediated.
        Neurosci Lett. 2006; 401: 256-260
        • Kosek E.
        • Hansson P.
        Modulatory influence on somatosensory perception from vibration and heterotopic noxious conditioning stimulation (HNCS) in fibromyalgia patients and healthy subjects.
        Pain. 1997; 70: 41-51
        • 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
        • Lautenbacher S.
        • Rollman G.B.
        Possible deficiencies of pain modulation in fibromyalgia.
        Clin J Pain. 1997; 13: 189-196
        • Le Bars D.
        • Dickenson A.H.
        • Besson J.M.
        Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat.
        Pain. 1979; 6: 283-304
        • Le Bars D.
        • Dickenson A.H.
        • Besson J.M.
        Diffuse noxious inhibitory controls (DNIC). II. Lack of effect on non-convergent neurones, supraspinal involvement and theoretical implications.
        Pain. 1979; 6: 305-327
        • LeResche L.
        • Mancl L.
        • Sherman J.J.
        • Gandara B.
        • Dworkin S.F.
        Changes in temporomandibular pain and other symptoms across the menstrual cycle.
        Pain. 2003; 106: 253-261
        • Monks D.A.
        • Arciszewska G.
        • Watson N.V.
        Estrogen-inducible progesterone receptors in the rat lumbar spinal cord: Regulation by ovarian steroids and fluctuation across the estrous cycle.
        Horm Behav. 2001; 40: 490-496
        • Okifuji A.
        • Turk D.C.
        Sex hormones and pain in regularly menstruating women with fibromyalgia syndrome.
        J Pain. 2006; 7: 851-859
        • Parsons C.M.
        Effect of induced pain on pain threshold.
        Proc Soc Exp Biol Med. 1945; 60: 327-329
        • Pud D.
        • Granovsky Y.
        • Yarnitsky D.
        The methodology of experimentally induced diffuse noxious inhibitory control (DNIC)-like effect in humans.
        Pain. 2009; 144: 16-19
        • Rezaii T.
        • Ernberg M.
        Influence of oral contraceptives on endogenous pain control in healthy women.
        Exp Brain Res. 2010; 203: 329-338
        • 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
        • Riley III, 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
        • Sherman J.J.
        • LeResche L.
        Does experimental pain response vary across the menstrual cycle? A methodologic review.
        Am J Physiol Regul Integr Comp Physiol. 2006; 291: R245-R256
        • Simonian S.X.
        • Herbison A.E.
        Differential expression of estrogen receptor and neuropeptide Y by brainstem A1 and A2 noradrenaline neurons.
        Neuroscience. 1997; 76: 517-529
        • Smith Y.R.
        • Stohler C.S.
        • Nichols T.E.
        • Bueller J.A.
        • Koeppe R.A.
        • Zubieta J.K.
        Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women.
        J Neurosci. 2006; 26: 5777-5785
        • Södergård R.
        • Backström T.
        • Shanbhag V.
        • Carstensen H.
        Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature.
        J Steroid Biochem. 1982; 16: 801-810
        • Spielberger C.D.
        The measurement of state and trait anxiety: Conceptual and methodological issues.
        in: Levi L. Emotions-Their Parameters and Measurement. Raven Press, New York, NY1975: 713-725
        • Staud R.
        Abnormal pain modulation in patients with spatially distributed chronic pain: Fibromyalgia.
        Rheum Dis Clin North Am. 2009; 35: 263-274
        • 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
        • Tashiro A.
        • Okamoto K.
        • Bereiter D.A.
        NMDA receptor blockade reduces temporomandibular joint-evoked activity of trigeminal subnucleus caudalis neurons in an estrogen-dependent manner.
        Neuroscience. 2009; 164: 1805-1812
        • Teepker M.
        • Peters M.
        • Vedder H.
        • Schepelmann K.
        • Lautenbacher S.
        Menstrual variation in experimental pain: Correlation with gonadal hormones.
        Neuropsychobiology. 2010; 61: 131-140
        • Tousignant-Laflamme Y.
        • Marchand S.
        Excitatory and inhibitory pain mechanisms during the menstrual cycle in healthy women.
        Pain. 2009; 146: 47-55
        • Unruh A.M.
        Gender variations in clinical pain experience.
        Pain. 1996; 65: 123-167
        • Wand-Tetley J.I.
        Historical methods of counter-irritation.
        Ann Phys Med. 1956; 3: 90-99
        • Viana Ede S.
        • Bruno S.S.
        • Sousa M.B.
        Modulation by progesterone of pain sensitivity to mechanical and ischemic stimuli in young and healthy women.
        Rev Bras Ginecol Obstet. 2008; 30: 306-311
        • Willer J.C.
        • Le Bars D.
        • De Broucker T.
        Diffuse noxious inhibitory controls in man: Involvement of an opioidergic link.
        Eur J Pharmacol. 1990; 182: 347-355
        • Yarnitsky D.
        • Arendt-Nielsen L.
        • Bouhassira D.
        • Edwards R.R.
        • Fillingim R.B.
        • Granot M.
        • Hansson P.
        • Lautenbacher S.
        • Marchand S.
        • Wilder-Smith O.
        Recommendations on terminology and practice of psychophysical DNIC testing.
        Eur J Pain. 2010; 14: 339