Pain perception in women with menstrually-related migraine

Background Cyclic hormonal fluctuations influence migraine incidence and severity. Previously, we described reduced menstrual cyclicity in estradiol levels and dermal blood flow reaction to capsaicin in female migraineurs. It is unclear whether pain perception in women with migraine is influenced by the menstrual cycle. Methods Women with menstrually-related migraine (n = 14), healthy age-matched controls (n = 10) and postmenopausal women (n = 15) were asked to grade trigeminal and non-trigeminal painful stimuli on a numeric pain rating scale on menstrual cycle day 19–21 (mid-luteal) and day 1–2 (early follicular). Results In women with menstrually-related migraine, trigeminal pain remained low throughout the cycle. Controls showed increased trigeminal pain during the mid-luteal phase compared to the early follicular phase. Changes throughout the cycle were significantly different between women with MRM and controls. Conclusion The compromised menstrual cyclicity of pain perception in women with menstrually-related migraine parallels our earlier findings on estradiol levels and dermal blood flow.

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Influence of menstrual cycle on shivering, skin blood flow, and sweating responses measured at night

Journal of Applied Physiology ◽

10.1152/jappl.1985.59.6.1902 ◽

1985 ◽

Vol 59 (6) ◽

pp. 1902-1910 ◽

Cited By ~ 86

Author(s):

V. Hessemer ◽

K. Bruck

Keyword(s):

Blood Flow ◽

Menstrual Cycle ◽

Body Temperature ◽

Sweat Rate ◽

Serum Progesterone ◽

Mean Body Temperature ◽

Cutaneous Vasodilation ◽

Threshold Temperatures ◽

Early Follicular Phase ◽

Heat Clearance

In 10 women, external cold and heat exposures were performed both in the middle of luteal phase (L) and in the early follicular phase (F) of the menstrual cycle. Serum progesterone concentrations in L and F averaged 46.0 and 0.9 nmol X l-1, respectively. The experiments took place between 3:00 and 4:30 A.M., when the L-F core temperature difference is maximal. At neutral ambient temperature, esophageal (Tes), tympanic (Tty), rectal (Tre), and mean skin (Tsk) temperatures averaged 0.59 degrees C higher in L than in F. The thresholds for shivering, chest sweating, and cutaneous vasodilation (heat clearance technique) at the thumb and forearm were increased in L by an average of 0.47 degrees C, related to mean body temperature [Tb(es) = 0.87Tes + 0.13 Tsk] and to Tes, Tty, Tre, or Tsk. The above-threshold chest sweat rate and cutaneous heat clearances at the thumb and forearm were also enhanced in L, when related to Tb(es) or time. The metabolic rate, arm blood flow, and heart rate at thermoneutral conditions were increased in L by 5.0%, 1.1 ml X 100 ml-1 X min-1, and 4.6 beats X min-1, respectively. The concomitant increase in threshold temperatures for all autonomic thermoregulatory responses in L supports the concept of a resetting of the set point underlying the basal body temperature elevation in L. The effects of the increased threshold temperatures are counteracted by enhanced heat loss responses.

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Effect of luteal phase elevation in core temperature on forearm blood flow during exercise

Journal of Applied Physiology ◽

10.1152/jappl.1997.82.4.1079 ◽

1997 ◽

Vol 82 (4) ◽

pp. 1079-1083 ◽

Cited By ~ 50

Author(s):

Margaret A. Kolka ◽

Lou A. Stephenson

Keyword(s):

Blood Flow ◽

Menstrual Cycle ◽

Core Temperature ◽

Luteal Phase ◽

Forearm Blood Flow ◽

Venous Occlusion ◽

Follicular Phase ◽

Dew Point ◽

Early Follicular Phase ◽

Midluteal Phase

Kolka, Margaret A., and Lou A. Stephenson. Effect of luteal phase elevation in core temperature on forearm blood flow during exercise. J. Appl. Physiol. 82(4): 1079–1083, 1997.—Forearm blood flow (FBF) as an index of skin blood flow in the forearm was measured in five healthy women by venous occlusion plethysmography during leg exercise at 80% peak aerobic power and ambient temperature of 35°C (relative humidity 22%; dew-point temperature 10°C). Resting esophageal temperature (Tes) was 0.3 ± 0.1°C higher in the midluteal than in the early follicular phase of the menstrual cycle ( P < 0.05). Resting FBF was not different between menstrual cycle phases. The Tes threshold for onset of skin vasodilation was higher (37.4 ± 0.2°C) in midluteal than in early follicular phase (37.0 ± 0.1°C; P < 0.05). The slope of the FBF to Tes relationship was not different between menstrual cycle phases (14.0 ± 4.2 ml ⋅ 100 ml−1 ⋅ min−1 ⋅ °C−1for early follicular and 16.3 ± 3.2 ml ⋅ 100 ml−1 ⋅ min−1 ⋅ °C−1for midluteal phase). Plateau FBF was higher during exercise in midluteal (14.6 ± 2.2 ml ⋅ 100 ml−1 ⋅ min−1 ⋅ °C−1) compared with early follicular phase (10.9 ± 2.4 ml ⋅ 100 ml−1 ⋅ min−1 ⋅ °C−1; P < 0.05). The attenuation of the increase in FBF to Tes occurred when Tes was 0.6°C higher and at higher FBF in midluteal than in early follicular experiments ( P < 0.05). In summary, the FBF response is different during exercise in the two menstrual cycle phases studied. After the attenuation of the increase in FBF and while Tes was still increasing, the greater FBF in the midluteal phase may have been due to the effects of increased endogenous reproductive endocrines on the cutaneous vasculature.

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The influence of migraine and female hormones on capsaicin-induced dermal blood flow

Cephalalgia ◽

10.1177/0333102416668659 ◽

2016 ◽

Vol 37 (12) ◽

pp. 1164-1172 ◽

Cited By ~ 13

Author(s):

Khatera Ibrahimi ◽

Steve Vermeersch ◽

Pascal Frederiks ◽

Vincent Geldhof ◽

Cedric Draulans ◽

...

Keyword(s):

Blood Flow ◽

Menstrual Cycle ◽

Sex Hormones ◽

Healthy Subjects ◽

Secretory Phase ◽

Female Sex ◽

Female Sex Hormones ◽

Calcitonin Gene ◽

Late Secretory Phase ◽

Dermal Blood Flow

Background Migraine is much more common in females than in males, and occurrence is associated with changes in female sex hormones. Calcitonin gene-related peptide (CGRP) plays a key role in migraine, and variations in female sex hormones may affect CGRP sensitivity and/or production. Objectives Investigate repeatability, gender differences, influence of the menstrual cycle and of migraine on CGRP-dependent changes in dermal blood flow (DBF). Methods CGRP-dependent increases in DBF were assessed using laser Doppler perfusion imaging after topical application of 300 or 1000 µg capsaicin on the forearm of healthy subjects and migraine patients. Results In healthy males, DBF response did not vary over time and was comparable with DBF in male migraineurs. In healthy females, capsaicin-induced DBF responses to both doses of capsaicin were higher during menstruation compared to the late-secretory phase (p < 0.05); this menstrual cycle dependence was absent in female migraine patients. Compared to healthy subjects, female migraineurs displayed a higher DBF response both during menstruation and during the late-secretory phase (p < 0.05). Conclusions An increased capsaicin-induced, CGRP-mediated DBF response was observed during menstruation in healthy women, but in female migraine patients this increased response was not affected by the menstrual cycle.

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Effects of estradiol on measurements of conduit artery endothelial function after ischemia and reperfusion in premenopausal women

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2015-0589 ◽

2016 ◽

Vol 94 (12) ◽

pp. 1304-1308 ◽

Cited By ~ 10

Author(s):

Mary Clare Luca ◽

Andrew Liuni ◽

Paula Harvey ◽

Susanna Mak ◽

John D. Parker

Keyword(s):

Menstrual Cycle ◽

Ischemia Reperfusion ◽

Premenopausal Women ◽

Follicular Phase ◽

Flow Mediated Dilatation ◽

Before And After ◽

Early Follicular Phase ◽

First Time ◽

Late Follicular Phase ◽

Estradiol Levels

In premenopausal women, ovarian steroids are felt to play a role in the prevention of cardiovascular disease. We aimed to assess whether menstrual cycle variations in estrogen can modify the response to ischemia–reperfusion (IR) injury in humans. In an investigator-blinded crossover study, 10 healthy premenopausal women with regular menstrual cycles were studied. They had flow-mediated dilatation (FMD) measured by ultrasound in the radial artery before and after IR (15 min of brachial artery ischemia, 15 min of reperfusion) during both the early and late follicular phases of the menstrual cycle. The order of these visits was not randomized. IR significantly blunted FMD in the early follicular phase (pre-IR: 7.1% ± 1.0%; post-IR: 3.6% ± 1.0%, P = 0.01) when estradiol levels were low (148.4 ± 19.8 pmol/L). Conversely, FMD was preserved after IR during the late follicular phase (pre-IR: 7.2% ± 0.9%; post-IR: 7.0% ± 0.8%, P = NS, P = 0.03 compared with early follicular) when estradiol levels were high (825.7 ± 85.8 pmol/L, P < 0.001 compared with early follicular). There was a significant inverse relationship between estradiol concentration and IR-induced endothelial dysfunction (i.e., change in FMD after IR) (r = 0.59, r2 = 0.36, P < 0.01). These findings demonstrate, for the first time in humans, a clear relationship between the cyclical changes in serum concentrations of estradiol and the endothelium’s response to IR.

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Assessment of pain perception and pressure threshold for pain changes during the premenstrual phase of the menstrual cycle

10.25148/etd.fi14061563 ◽

1996 ◽

Author(s):

Lisa Marie Cullen

Keyword(s):

Menstrual Cycle ◽

Pain Perception ◽

Pressure Threshold

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Comparison of pregnenolone sulfate, pregnanolone and estradiol levels between patients with menstrually-related migraine and controls: an exploratory study

The Journal of Headache and Pain ◽

10.1186/s10194-021-01231-9 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Cecilia Rustichelli ◽

Elisa Bellei ◽

Stefania Bergamini ◽

Emanuela Monari ◽

Flavia Lo Castro ◽

...

Keyword(s):

Exploratory Study ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Allosteric Modulator ◽

Positive Allosteric Modulator ◽

Pregnenolone Sulfate ◽

Menstrually Related Migraine ◽

History Of ◽

Estradiol Levels

Abstract Background Neurosteroids affect the balance between neuroexcitation and neuroinhibition but have been little studied in migraine. We compared the serum levels of pregnenolone sulfate, pregnanolone and estradiol in women with menstrually-related migraine and controls and analysed if a correlation existed between the levels of the three hormones and history of migraine and age. Methods Thirty women (mean age ± SD: 33.5 ± 7.1) with menstrually-related migraine (MM group) and 30 aged- matched controls (mean age ± SD: 30.9 ± 7.9) participated in the exploratory study. Pregnenolone sulfate and pregnanolone serum levels were analysed by liquid chromatography-tandem mass spectrometry, while estradiol levels by enzyme-linked immunosorbent assay. Results Serum levels of pregnenolone sulfate and pregnanolone were significantly lower in the MM group than in controls (pregnenolone sulfate: P = 0.0328; pregnanolone: P = 0.0271, Student’s t-test), while estradiol levels were similar. In MM group, pregnenolone sulfate serum levels were negatively correlated with history of migraine (R2 = 0.1369; P = 0.0482) and age (R2 = 0.2826, P = 0.0025) while pregnenolone sulfate levels were not age-related in the control group (R2 = 0.04436, P = 0.4337, linear regression analysis). Conclusion Low levels of both pregnanolone, a positive allosteric modulator of the GABAA receptor, and pregnenolone sulfate, a positive allosteric modulator of the NMDA receptor, involved in memory and learning, could contribute either to headache pain or the cognitive dysfunctions reported in migraine patients. Overall, our results agree with the hypothesis that migraine is a disorder associated with a loss of neurohormonal integrity, thus supporting the therapeutic potential of restoring low neurosteroid levels in migraine treatment.

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A preliminary study exploring the change in ankle joint laxity and general joint laxity during the menstrual cycle in cis women

Journal of Foot and Ankle Research ◽

10.1186/s13047-021-00459-7 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Tomomi Yamazaki ◽

Sae Maruyama ◽

Yuki Sato ◽

Yukako Suzuki ◽

Sohei Shimizu ◽

...

Keyword(s):

Menstrual Cycle ◽

Ankle Joint ◽

Length Change ◽

Joint Laxity ◽

Anterior Talofibular Ligament ◽

Menstrual Phase ◽

Anterior Drawer ◽

Linear Distance ◽

Significant Difference ◽

Early Follicular Phase

Abstract Background The purpose of the present study was to examine the relationship between ankle joint laxity and general joint laxity (GJL) in relation to the menstrual cycle, which was divided into four phases based on basal body temperature and ovulation, assessed using an ovulation kit. Methods Participants were 14 female college students (21–22 years) with normal menstrual cycles (cis gender). Anterior drawer stress to a magnitude of 120 N was applied for all participants. Anterior talofibular ligament (ATFL) length was measured as the linear distance (mm) between its points of attachment on the lateral malleolus and talus using ultrasonography. Data on ATFL length from each subject were used to calculate each subject’s normalized length change with anterior drawer stress (AD%). The University of Tokyo method was used for evaluation of GJL. AD% and GJL were measured once in each menstrual phase. Results There was no statistically significant difference between AD% in each phase. GJL score was significantly higher in the ovulation and luteal phases compared with the early follicular phase. AD% and GJL showed a positive correlation with each other in the ovulation phase. Conclusions Although it is unclear whether estrogen receptors are present in the ATFL, the present study suggests that women with high GJL scores might be more sensitive to the effects of estrogen, resulting in ATFL length change in the ovulation phase.

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Menstrual cycle phase and time of day alter reference signal controlling arm blood flow and sweating

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1985.249.2.r186 ◽

1985 ◽

Vol 249 (2) ◽

pp. R186-R191 ◽

Cited By ~ 29

Author(s):

L. A. Stephenson ◽

M. A. Kolka

Keyword(s):

Blood Flow ◽

Menstrual Cycle ◽

Water Vapor Pressure ◽

Reference Signal ◽

Time Of Day ◽

Cycle Phase ◽

Menstrual Cycle Phase ◽

Cutaneous Vasodilation ◽

Effector Activity ◽

Exercise Transients

The changes occurring in the esophageal temperature (Tes) thresholds for initiation of heat loss responses as affected by the circadian period and menstrual cycle were studied. Four women exercised at 60% peak Vo2 in 35 degrees C (ambient water vapor pressure 1.73 kPa) for 30 min at 0400 and 1600 during the follicular (F) and luteal (L) phase. Tes, arm sweating rate (msw), and forearm blood flow (FBF) were measured frequently. At rest, Tes averaged 0.3 degrees C higher during L than F at both 0400 and 1600 and approximately 0.4 degrees C higher at 1600 than at 0400 during both phases. During exercise transients, the slopes of the FBF:Tes and the msw:Tes relationships were not different among treatments. The thresholds for initiation of sweating and cutaneous vasodilation were higher at 1600 than 0400 during both phases. Thresholds during F at 0400 averaged 36.44 degrees C for msw and 36.80 degrees C for vasodilation. The thresholds during L at 1600 averaged 37.46 and 37.53 degrees C for sweating and vasodilation, respectively. Our data indicate that the thermoregulatory effector activity during exercise is a function of numerous inputs, and one of these may be hormonal or hormonal-like in action. Controlling time of day and menstrual cycle phase are as important as controlling for aerobic power, age, and fitness in studying female thermoregulatory responses during exercise.

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