Sex-specific effects of neuropathic pain on long-term pain behavior and mortality in mice

Abstract

Supplemental Digital Content is Available in the Text.Mice were tested for pain after injury until death. Sex differences were observed in pain behavior over time and in the relationship between pain and lifespan.

Sexually Dimorphic Pattern of Pain Mitigation Following Prophylactic Regenerative Peripheral Nerve Interface (RPNI) in a Rat Neuroma Model

“…It is widely recognized that the use of sex-specific sham or control groups is crucial to control for baseline differences in pain sensitivity and pain-related behaviors between males and females. 6,24,25 These differences may be the result of the influence of sex hormones on the nervous system, variations in the expression of certain genes and receptors, or even differences in baseline pain sensitivity and behavior. 24,[26][27][28][29] These led to The National Institute of Health policy on Rigor and Reproducibility (Notice of Transparency 15-102 and Notice of Transparency 16-011), which emphasizes the importance of sex as a biological variable to research investigation.…”

Spared nerve injury decreases motivation in long-access homecage-based operant tasks in mice

“…Efforts to support larger scale or multisite, preclinical studies should help overcome some of these limitations. 10,64,68 Altogether, we used a battery of behavior tests often used to study negative affective behavior to determine the neuropsychiatric impact of long-term neuropathic injury in C57BL/6J mice. Although our most notable single results were from homecagebased, long-access operant tasks, we have also demonstrated that normalized behavioral scores across a battery of assays can identify generalized negative affective states induced by chronic…”

Chronic pain and premature mortality in men and women, using data from UK Biobank. Reply.

“…Our original analysis asked if there was a relationship between age at death and pain severity. We were particularly interested in pain severity as an independent measure, as opposed to simple presence of chronic widespread pain (CWP), because of the results of our recent paper ( 3 ) — which, although not yet published, were known to us at the time — showing a correlation between pain severity and lifespan in male but not female mice. Pain severity data have only been made available recently in the UKB, and these data only reflect a subset of participants.…”

“…The bigger question of whether there is indeed a sex-specific relationship between chronic pain and longevity in humans, as there clearly is in mice ( 1 , 3 ), remains open; a more definitive answer will be obtainable once survival percentages descend to approximately 50%. We would remind the reader, however, that the main focus of our paper ( 1 ) was the sex-dependent role of telomere dysfunction and cellular senescence on chronic pain (e.g., the male-specific TP53 gene association), not sex‑dependent pain epidemiology per se.…”