A meta-analytic review of pain perception across the menstrual cycle

Abstract

The purpose of this article is to review the sixteen published studies that examine associations between the perception of experimentally induced pain across menstrual cycle phases of healthy females. We also performed a meta-analysis to quantitatively analyze the data and attempt to draw conclusions. The results suggest that there are relatively consistent patterns in the sensitivity to painful stimulation. These patterns are similar across stimulus modality with the exception of electrical stimulation. The magnitude of the effect was approximately 0.40 across all stimulation. For pressure stimulation, cold pressor pain, thermal heat stimulation, and ischemic muscle pain, a clear pattern emerges with the follicular phase demonstrating higher thresholds than later phases. When the effect size was pooled across studies (excluding electrical) comparisons involving the follicular phase were small to moderate (periovulatory phase, d(thr) = 0.34; luteal phase, d(thr) = 0.37; premenstrual phase, d(thr) = 0.48). The pattern of effects was similar for tolerance measures. Electrical stimulation was different than the other stimulus modalities, showing the highest thresholds for the luteal phase. When the effect size was pooled across studies for electrical stimulation, effect sizes were small to moderate (menstrual (d(thr) = -0.37), follicular d(thr) = -0.30) periovulatory d(thr) = -0.61), and premenstrual d(thr) = 0.35) phases. This paper raises several important questions, which are yet to be answered. How much and in what way does this menstrual cycle effect bias studies of female subjects participating in clinical trials? Furthermore, how should studies of clinical pain samples control for menstrual related differences in pain ratings and do they exist in clinical pain syndromes? What this paper does suggest is that the menstrual cycle effect on human pain perception is too large to ignore.

Caveolin proteins and estrogen signaling in the brain

“…Thus far, it has been determined that caveolin proteins functionally link estrogen receptors with mGluRs in striatal neurons [92]; other regions await verification. Through influencing these additional regions, rapid estrogen receptor signaling has been suggested to modulate multiple cellular processes, such as motor control and drug addiction [12,[95][96][97], sexual receptivity [91], the control of the estrous cycle [98], and nociception [14,99]. Furthermore, while we and others hypothesize GPCRs to act as intermediaries between estrogen receptors and G proteins, others have postulated that estrogen receptors directly activate the G proteins [100].…”

“…However, in addition to its actions on intracellular estrogen receptors, estradiol can also affect a variety of cellular processes through stimulation of surface membrane receptors. Not only have these rapid acting effects of estrogens been shown to play a role in sex behavior, but also in brain and spinal cord regions involved with, but not limited to, learning and memory, motor function, nociception and drug addiction [9][10][11][12][13][14][15]. The majority of these reported membrane-initiated actions of estradiol in the nervous system appear dependent on a subpopulation of ERα and/ or ERβ that are localized to the membrane surface [16][17][18], but see [19][20][21].…”

The effects of menstrual-related pain on attentional interference

“…The second phase was a non-pain/pain free day, and was defined as the midfollicular phase, prior to ovulation. This phase was chosen because previous studies suggest that pain sensitivity is relatively low [24], and was determined by counting from the first day of menstruation i.e., days 5-9 of an average 28-day cycle.…”

Anxiety sensitivity and pain: Generalisability across noxious stimuli

“…Order of pain stimuli was counterbalanced within gender, with half of the participants receiving the cold followed by the heat stimulus, with this order reversed for the remaining half. Resting blood pressure, menstrual phase and negative mood state were also recorded, as previous research has suggested that these may operate as potential process variables underlying sex and anxiety sensitivity differences in pain (Fillingim and Maixner, 1996;Keogh and Birkby, 1999;Riley et al, 1999).…”