Sex differences in pain expressed by patients across diverse disease states: individual patient data meta-analysis of 33,957 participants in 10 randomized controlled trials

Abstract

The experience of pain is determined by many factors and has a significant impact on quality of life. This study aimed to determine sex differences in pain prevalence and intensity reported by participants with diverse disease states in several large international clinical trials. Individual participant data meta-analysis was conducted using EuroQol-5 Dimension (EQ-5D) questionnaire pain data from randomised controlled trials published between January 2000 and January 2020 and undertaken by investigators at the George Institute for Global Health. Proportional odds logistic regression models, comparing pain scores between females and males and fitted with adjustments for age and randomized treatment, were pooled in a random-effects meta-analysis. In 10 trials involving 33,957 participants (38% females) with EQ-5D pain score data, the mean age ranged between 50 and 74. Pain was reported more frequently by females than males (47% vs 37%; P < 0.001). Females also reported greater levels of pain than males (adjusted odds ratio 1.41, 95% CI 1.24-1.61; P < 0.001). In stratified analyses, there were differences in pain by disease group (P for heterogeneity <0.001), but not by age group or region of recruitment. Females were more likely to report pain, and at a higher level, compared with males across diverse diseases, all ages, and geographical regions. This study reinforces the importance of reporting sex-disaggregated analysis to identify similarities and differences between females and males that reflect variable biology and may affect disease profiles and have implications for management.

Identifying the function of the NMDA NR1C2subunit through its interaction with Magi-2 during inflammatory pain

“…We have previously noted that CFA inflammatory pain in males and females differed in response to afferent activity manipulation; female inflammatory pain appears to have more of a central component 52 . This data corroborates those findings and is consistent with the sex differences in pain observed in humans 53,54 .…”

Investigating the fluctuating nature of post-COVID pain symptoms in previously hospitalized COVID-19 survivors: the LONG-COVID-EXP multicenter study

“…Therefore, future management of post-COVID pain should be applied from a sex perspective considering biological and psychological differences. 18…”

“…Therefore, future management of post-COVID pain should be applied from a sex perspective considering biological and psychological differences. 18 Previous history of painful conditions was another factor associated with a higher risk of developing post-COVID pain. We found that up to 40% of our sample experienced pain symptoms before SARS-CoV-2 infection.…”

Differential Effects of Regulatory T Cells in the Meninges and Spinal Cord of Male and Female Mice with Neuropathic Pain

“…Sex differences in pain studies are now well established. Evidence indicates that women are more likely to suffer from chronic pain [ 22 ] and report higher pain levels than men across diverse diseases, ages, and geographical regions [ 23 ]. Although the mechanisms underlying these sex differences are not fully understood, recent studies have revealed a sex-specific involvement of different genes, proteins, hormones, and cellular responses with distinct effects on immune function, influencing pain signalling [ 24 ].…”