Gender Differences in Pain Threshold, Unpleasantness, and Descending Pain Modulatory Activation Across the Adult Life Span: A Cross Sectional Study

• Published in: The journal of pain Vol. 25; no. 4; pp. 1059 - 1069
• Main Authors: Failla, Michelle D., Beach, Paul A., Atalla, Sebastian, Dietrich, Mary S., Bruehl, Stephen, Cowan, Ronald L., Monroe, Todd B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2024
• Subjects: Adult; Brain - diagnostic imaging; Brain Mapping - methods; Cross-Sectional Studies; Evoked pain; Female; FMRI; Gender differences; Humans; Longevity; Magnetic Resonance Imaging - methods; Male; Neuroimaging; Pain; Pain Threshold - physiology; Sex Factors; Succinimides; Thermal pain; Neuroimaging; Gender differences; Thermal pain; Evoked pain; FMRI
• ISSN: 1526-5900; 1528-8447; 1528-8447
• DOI: 10.1016/j.jpain.2023.10.027

The neurobiological underpinnings of gender differences in pain perception, and how these differences may be modified by age, are incompletely understood, placing patients at risk of suboptimal pain management. Using functional magnetic resonance imaging, we examined brain responses in the descending pain modulatory system (DPMS, specifically, dorsolateral prefrontal cortex, anterior cingulate cortex, insula, hypothalamus, amygdala, and periaqueductal gray, during an evoked pain task. We investigated the interaction of age and gender in our sample of healthy adults (27 females, 32 males, 30–86 years) on DPMS response. In a perceptually matched thermal pain paradigm, we investigated pain unpleasantness and neural responses for 3 heat pain percepts: just noticeable pain, weak pain, and moderate pain (MP). Females reported just noticeable pain at a lower temperature, but reported less unpleasantness at weak pain and MP percepts, compared to males. There was a significant age-by-gender interaction during moderate pain in the right anterior cingulate cortex and bilateral insula, such that, males had a stronger positive relationship between DPMS response and age compared to females in these regions. Our results indicate that differences in DPMS responses may explain some gender differences in pain perception and that this effect may change across the adult lifespan. Gender differences in pain have been well-documented but the brain mechanisms for these differences are still unclear. This article describes potential differences in brain functioning during different levels of pain that could explain differences in pain responses between men and women across the adult lifespan. •Both age and gender may impact pain perception in adults age 30 to 89.•Descending pain modulation may be a source of underlying gender differences in pain.•Age and gender interact in response to evoked pain in the insula and cingulate cortex.•Assessing pain unpleasantness may improve gender-specific identification of pain.