Sex differences in the cerebral BOLD signal response to painful heat stimuli

Abstract

There are limited data addressing the question of sex differences in pain-related cerebral processing. This study examined whether pain-related blood oxygenation level-dependent (BOLD) signal change measured with functional magnetic resonance imaging (fMRI) demonstrated sex differences, under conditions of equivalent pain perception. Twenty-eight healthy volunteers (17 women, 11 men) were subject to a fMRI scan while noxious heat stimuli were applied to the dorsum of the left foot. Significant BOLD signal modulation was observed in several nociceptive processing regions of interest (ROIs) in all subjects. There were no sex differences in the spatial extent of BOLD signal change for any ROI, but the signal amplitude was lower for women in most ROIs and significantly so for the primary somatosensory cortex (S1), the midanterior cingulate cortex, and the dorsolateral prefrontal cortex (DLPFC). The BOLD signal response could be positive or negative, and frequently, both polarities were observed within a single ROI. In most ROIs, women show proportionately more voxels with negative signal change than men, and this difference was statistically significant for the S1 and the DLPFC. The time course of the negative signal change was very similar to that of the positive signal change, suggesting that the latter was not "driving" the former. The location of negative and positive clusters formed distinct patterns in several of the ROIs, and these patterns suggest something other than a local "steal" phenomenon as an explanation for the negative signal changes. Sex differences in baseline cerebral blood flow may contribute to the BOLD signal differences observed in this study. nociception; fMRI; somatosensory cortex; neuroimaging; prefrontal cortex; negative blood oxygenation level-dependent signal A NUMBER OF STUDIES HAVE FOUND that women are more sensitive to experimental painful stimulation than men. Yet, this is neither a universal nor large effect, given that no differences are found in approximately one-third of the published studies, and statistically significant differences are often in the smallto-moderate range (9, 27). Nonetheless, enough of a difference is found with enough regularity to suggest that women and men may perceive painful stimuli differently. Related to this are observations from both animal and human studies that nociceptive processing may be different between men and women, thereby providing a basis for sex differences in perception and behavior (7,19).Only a few neuroimaging studies have reported sex differences in cerebral responses to noxious stimuli. A 15 O-positron emission tomography (PET) study reported significantly greater activation in women vs. men in several regions of interest (ROIs) in response to noxious heat (24). In that report, sex differences in the PET results may have been related to sex differences in perceived pain intensity. In contrast, a subsequent PET study reported significantly greater activation in men vs. women in some of the same ROIs in response to painful laser sti...

Sex differences in regional brain response to aversive pelvic visceral stimuli

“…In view of our earlier findings in IBS patients of greater limbic and paralimbic activation in female patients, one may speculate that a breakdown in these counter regulatory mechanisms in women results in a maladaptive activation of arousal systems during physiological visceral stimuli. In combination with the results of Moulton and associates (39), the present data suggest that the tendency of healthy women to elicit more deactivation, or inhibition, may be a general sex-related characteristic and applies to both cortical and subcortical structures. Further research is needed with larger samples to ascertain the relative strength of these effects in different structures.…”

“…However, the recent presentation of similar sex-related differences in response to a somatic pain stimulus by Moulton and associates (39) and the previous report of greater BOLD signal decreases in women in response to rectal distension (2, 10) increase our confidence in these findings. In addition, we have not discussed sex differences in the peak signal amplitude within each region as we have signal spatial extent, nor have we explored possible sex differences in signal time-course and within-region localization of activations relative to deactivations.…”

“…In addition, we have not discussed sex differences in the peak signal amplitude within each region as we have signal spatial extent, nor have we explored possible sex differences in signal time-course and within-region localization of activations relative to deactivations. Although previous studies (27,39) and our own investigations to date have not found strong sex differences in these measures (5-8), they are important in characterizing sex differences in brain response and further analyses, as well as additional studies, are in progress.…”

Sex and gender differences in pain and inflammation: a rapidly maturing field

“…Thirteen papers are published in this issue; another one was published earlier this year (13); several more are in the review process. The studies accepted for the call so far run the gamut from research with humans involving brain imaging (1,17), psychophysics (8), methodology (18), and a study focused on men (19) to research with animals involving actions of analgesics, such as morphine (5,16,20), nonsteroidal anti-inflammatory agents (9), and acid-sensing ion channels (6), actions of hormones (11,12), cannabinoid molecular biology of the entire brain (3), and psychosocial issues (13).…”

Chronic cough hypersensitivity syndrome

“…В исследованиях с использованием магнитно резонансной томогра фии у женщин и мужчин наблюдались различные паттерны активации головного мозга в ответ на фи зические или термические раздражители [20][21][22] и кашель [23].…”