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Pain Perception in Women With Dysmenorrhea

From the Department of Obstetrics and Gynecology and Department of Neurophysiology, Rambam Medical Center, Technion Faculty of Medicine, Haifa, Israel.

Address reprint requests to: E. Z. Zimmer, MD, Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa, 31096 Israel; E-mail: etan{at}tx.technion.ac.il.

	ABSTRACT

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
OBJECTIVE: To determine if systemic processing of pain differs in women with and without dysmenorrhea.

METHODS: Twenty-two dysmenorrheic women and 31 nondysmenorrheic women were studied by pain threshold and supra-threshold magnitude estimation to heat stimuli, pain-evoked potentials by laser stimuli, and anxiety scores four times across their menstrual cycles.

RESULTS: Significant differences were found between dysmenorrheic and nondysmenorrheic women. In all four examinations across the menstrual cycle, dysmenorrheic women had longer latencies of pain-evoked potentials (383.08 ± 6.8 msec versus 345.05 ± 7.0 msec, P < .001), higher magnitude estimations on visual analog scale of supra-threshold pain (83.29 ± 2.87 versus 63.50 ± 3.82, P < .001), and higher state anxiety scores (37.69 ± 1.7 versus 29.20 ± 1.9, P = .002).

CONCLUSION: Women with dysmenorrhea show enhanced pain perception compared to nondysmenorrheic women. This augmentation of pain perception may be part of the development of dysmenorrhea.

Dysmenorrhea occurs in about 15–50% of young women and is the leading cause of school and work absence in this age group.¹ It has been shown that women with dysmenorrhea have increased likelihood of additional pain syndromes such as migraine,² fibromyalgia,³ and irritable bowel disorder.⁴ They have also been reported to be more susceptibile to psychologic disorders such as depression, anxiety, and somatization,⁵ as well as to be more likely to give histories of childhood physical and sexual abuse.⁶ Therefore, it may be that dysmenorrheic women have a different mode of systemic pain processing, such that the peripheral nociceptive message induced by uterine activity during menstruation is augmented to a larger extent as compared with nondysmenorrheic women. The present study was designed to compare pain perception and processing in dysmenorrheic and nondysmenorrheic women. A multidimensional approach with subjective and objective pain assessment tools was used.

	MATERIALS AND METHODS

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Because dysmenorrhea occurs in 15–50% of young women, it was estimated that a study group of about 20–25 dysmenorrheic women and a similar number of nondysmenorrheic controls would identify differences of at least two standard deviations in pain perception scoring between the two groups of women. The study was approved by the Rambam Medical Center Review Board in accordance with the Declaration of the Health Helsinki. College students from the Faculty of Health Sciences volunteered for the study and gave written informed consent. Women with systemic disease, or hormonal, psychiatric or gynecologic disorders, or substance abuse were excluded. Included were healthy Jewish white nulligravid women between 19–30 years of age who had regular menstrual cycles (28–33 days) and had not used oral contraceptives for at least half a year. During the study period of 6 months, 53 women fulfilled the inclusion criteria. Twenty-two women had dysmenorrhea and 31 did not. Dysmenorrhea was defined as severe cramping abdominal pain associated with symptoms such as fatigue, nausea, headache, or diarrhea, and use of analgesic treatment, which caused disability or absence from work on the first days of menstruation.

The women were examined four times across the menstrual cycle: first or second day of menstruation; midfollicular phase, on days 5–9 of the cycle; expected day of ovulation, days 14–17 of the cycle; and midluteal phase, on days 21–24 of the cycle. The timing of each session was adjusted individually for each woman, according to the length of her menstrual cycle. Recordings were performed in the morning hours to reduce a possible circadian effect. Women were asked to avoid analgesics for 24 hours before study sessions, even if they suffered from pain. All sessions were similarly designed. First, women completed a questionnaire to score their level of anxiety; then a blood sample was taken for estrogen and progesterone. This was followed by assessment of spontaneous pain, pain threshold, and score of supra-threshold pain. Finally, laser stimuli were applied to the women’s hands and evoked potentials were recorded.

The Spielberger State-Trait Anxiety questionnaire administered to each subject has two parts.⁷ The first part assesses the level of anxiety state and the second part assesses the anxiety trait. Each part includes 20 statements that describe an emotional condition. Subjects are asked to rate their feelings about each sentence on a four-point scale. The anxiety level is determined by summing the scores of all 20 statements into a scale, which ranges from 20 to 80. An emotional state exists at a given moment in time and is characterized by subjective feelings of tension, apprehension, worry, and nervousness. Personality traits can be conceptualized as relatively enduring differences among people with specific tendencies to perceive the world in certain ways and in dispositions to react or behave in a specified manner with predictable regularity.

Plasma estradiol and progesterone levels were measured by radioimmunoassay employing the Solid-Phase kit (I-125) of the Coat-A-Count (DPC, Diagnostic Products Corporation, Los Angeles, CA). In each study session, subjects were asked to report the level of perceived spontaneous pain before the examination. Self-reports of pain were assessed by a 100-mm visual analog scale (VAS)⁸ ranging from "no pain" to "the worst pain imaginable."

The Quantitative Sensory Test was performed with a Thermal Sensory Analyzer (TSA-2001, Medoc, Israel), using a 30 x 46 mm² contact thermode. Pain threshold was determined by applying a thermode to the thenar eminence of the nondominant hand. The temperature was elevated from 32°C up to the point at which women reported that heat sensation became painful. To assess the supra-threshold magnitude of perceived pain, three stimuli of 4.5°C above the pain threshold were given, and the evoked perception was obtained on the VAS. Pain threshold is a specific point at the very end of the pain spectrum. The pain supra-threshold is a measure of amount of pain inflicted by stimuli above the threshold level. These two parameters may vary independently, and the measuring of both of them is warranted.

Pain-evoked potentials were elicited by stimuli produced by a water-cooled CO₂ laser (D48-2-28W, SynradInc., Mukilteo, WA). Stimulus generation was controlled by a computer, which was connected to a pulse generator (Master-8-VP, AMPI, Ramot, Israel). Electroencephalogram was recorded at multiple sites by means of a CEEGraph (Biologic, Mundeleing, IL). Electrodes were placed with a special cap (Electro-Cap Int., Eaton, OH), and measurements of latency and amplitude of the potentials were performed. The laser beam was directed to the area of the superficial radial nerve at the dorsal aspect of the hand, which is a nongynecological site. The stimulus elicited a painful sensation resembling a pin-prick. After determining the level of the stimulus and familiarizing the subjects with this kind of stimulation, one block of 30 stimuli with an interstimulus interval of 5 seconds was given, using a constant intensity. At the end of the block, subjects were asked to report, by means of the VAS, the level of overall pain induced by the laser stimulation. Full details of the recording procedure for pain-evoked potentials have been reported by our laboratory.⁹

Each variable, psychophysical and neurophysiological, was analyzed within a mixed-model analysis of variance with repeated measures with status (dysmenorrhea versus nondysmenorrhea), session (the four points across the menstrual cycle), and the interaction of status x session as independent factors.

	RESULTS

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All 53 women who volunteered for the study completed it. All were students in the Faculty of Health Sciences and their educational and socioeconomic status were similar. The mean ± standard deviation age of women with dysmenorrhea was 23.7 ± 2.8 years. In the control group, it was 24.1 ± 3.1 years. These differences were not significant. The estradiol and progesterone levels obtained confirmed that patients were evaluated at appropriate phases across the menstrual cycle (Table 1).

The score of self-reported endogenous pain as measured by the VAS was significantly higher during the menstruation period in dysmenorrheic women compared with nondysmenorrheic women (54.80 ± 1.6 versus 0.27 ± 1.83, P < .001), thus confirming that subjects were correctly assigned to the study and control groups. No significant differences in spontaneous pain were observed between both groups of patients in the other sessions of the study. No significant differences were found in the heat pain thresholds between the study and control groups (42.04 ± 0.51°C for dysmenorrheic women versus 41.37 ± 0.54°C for nondysmenorrheic women). Heat pain threshold did not change across the menstrual cycles.

The VAS scores for supra-threshold pain were significantly higher across the menstrual cycle in the dysmenorrheic women as compared with the nondysmenorrheic women (83.29 ± 2.87 versus 63.50 ± 3.82, P < .001). There were no significant differences in the VAS scoring between the four study sessions in either dysmenorrheic or nondysmenorrheic women. These results indicate that magnitude estimation of supra-threshold heat pain was not affected by the phase of the menstrual cycle or from the presence or absence of menstrual pain.

There was a significant session effect (menstrual cycle phase) on the latency and amplitude of the laser-evoked potentials in both groups. The longest latency and the highest amplitude were recorded during the follicular phase, whereas the shortest latency and the lowest amplitude were observed in the luteal phase (Table 2). Overall, dysmenorrheic women had significantly longer latencies in all study sessions compared with nondysmenorrheic women (383.08 ± 6.8 msec versus 345.05 ± 7.0 msec, P < .001) (Table 2). However, there was no significant difference between dysmenorrheic and nondysmenorrheic women regarding the evoked potential amplitude (23.26 ± 1.8 versus 25.53 ± 2.5).

	DISCUSSION

TOP ABSTRACT MATERIALS AND METHODS RESULTS DISCUSSION REFERENCES

 
We found that dysmenorrheic women differ from nondysmenorrheic women in perception and response to pain stimuli. Dysmenorrheic women had a longer latency of pain-evoked potentials, a higher psychophysical rating of pain, and a higher level of anxiety state. These findings were evident across the entire menstrual cycle and not only during menstruation. The study demonstrates that these changes represent a systemic phenomenon rather than a regional change in the pelvis because pain stimuli were applied to the patient’s hand, which obviously does not belong to the reproductive system.

We assessed systemic pain perception in our patients four times across the menstrual cycle and used two modes of pain stimuli—contact heat and laser stimuli. We observed no changes in response to heat stimuli across the menstrual cycle. However, laser pain stimuli elicited the longest latency and highest amplitude of evoked potentials in the follicular phase and the shortest latency and lowest amplitude of evoked potentials in the luteal phase. Previous studies on pain perception across the menstrual cycle revealed the following data.

Fillingim et al,¹⁰ who evaluated healthy women, found less ischemic pain sensitivity during the midfollicular phase as compared with the ovulatory and luteal phases, whereas thermal pain responses did not vary significantly across the menstrual cycle. Hapidou and Rollman¹¹ assessed both normally menstruating women and users of oral contraceptives. They measured pain sensitivity with palpation of rheumatological tender points and with pressure dolorimetry. The number of tender points identified by palpation was greater in the follicular phase as compared with the luteal phase. A meta-analysis¹² of 16 studies that examined pain perception across the menstrual cycle phases of healthy women revealed that the highest thresholds for pressure stimulation, cold pressure pain, thermal heat stimulation, and ischemic muscle pain were observed in the follicular phase while electrical stimulation was different, showing the highest thresholds in the luteal phase.

Considering pain perception in dysmenorrheic and nondysmenorrheic women, there are conflicting data in the literature. For instance, Goolkasian¹³ reported that the ability to discriminate between cold pressure painful and nonpainful stimuli varied cyclically in nondysmenorrheic women, whereas dysmenorrheic women showed a consistent pain reaction throughout the entire menstrual cycle. Amodei and Nelson-Gray¹⁴ did not find significant differences in pain thresholds and tolerance levels between dysmenorrheic and nondysmenorrheic women exposed to pressure pain. However, on a self-report measure of pain, patients with severe dysmenorrhea reported the highest degree of pain and distress during the premenstrual and menstrual phases.

Giamberardino et al¹⁵ applied electrical stimulations to different segmental sites of the body. They found that the lowest pain sensitivity was in the luteal phase of both dysmenorrheic and nondysmenorrheic women. However, there were significant differences between both groups of patients regarding the modality and site of stimulation. For instance, changes in pain threshold were observed in nondysmenorrheic women only after stimulation of the abdominal muscle and subcutis, whereas in dysmenorrheic women such changes were also significant after stimulation of the abdominal skin and limb muscle and skin.

According to these previous studies, and our study as well, it seems that the menstrual phase, dysmenorrhea status, and modality of pain stimulation all have interacting effects on pain sensitivity. However, the relative significance of each of these variables needs further evaluation. The main limitation of studies that evaluate pain threshold and supra-threshold is that they rely on a subjective assessment of pain. The present study is of importance because pain-evoked potentials are an objective and quantitative pain assessment tool.^16,17

The amplitude of pain-evoked potentials reflects the extent of neural activation evoked by the stimulus, and bares relation to the intensity of perception. Decreased amplitude has been found in cases of spinal or peripheral diseases where loss of neurons caused a diminution of sensation.¹⁶ High amplitudes were found in cases of increased pain perception such as in fibromyalgia.¹⁸ The latency of pain-evoked potential reflects the time needed for processing sensory data. Stimuli of personal meaning delay the evoked potential response (increased latency) reflecting probably more elaborate processing before reaching a decision as expressed by the wave.¹⁹ We found that dysmenorrheic women had increased latency of pain-evoked potentials. It may be suggested that this finding reflects an increased impact of the pain message on the perception.

The present study suggests that dysmenorrhea is not necessarily determined solely by the inducing organ, the uterus, but may reflect an enhanced pain perception. However, further studies are needed to find out if dysmenorrheic women are susceptible to pain in general and therefore more apt to perceive dysmenorrhea, or if dysmenorrhea leads to a general lowering of the pain threshold such that women with it are secondarily more susceptible to having pain. Increasing our understanding of the pain mechanism will improve the treatment of these patients, which probably needs a multidisciplinary approach.

	Footnotes

 
We are indebted to Dr. Elliot Sprecher for his help in the analysis of data.

PII S0029-7844(01)01465-X

Received November 20, 2000. Received in revised form May 7, 2001. Accepted May 24, 2001.

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7. Spielberger CD. Current trends in theory and research on anxiety. In: Spielberger CD, ed. Anxiety — Current trends in theory and research. New York: Academic Press, 1972: 3–19.

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16. Treede RD. Evoked potentials related to pain. In: Boivie J, Hansson P, Lindblom U, eds. Touch, temperature, and pain in health and disease: Mechanisms and assessment.Seattle, WA: IASP Press, 1994:437–89.

17. Agostino R, Cruccu G, Romaniello A, Innocenti P, Inghilleri M, Manfredi M. Dysfunction of small myelinated afferents in diabetic polyneuropathy, as assessed by laser evoked potentials. Clin Neurophysiol 2000;111:270–6.[Medline]

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