Sex Differences in Pain: Spinal Cord Injury in Female and Male Mice Elicits Behaviors Related to Neuropathic Pain

Abstract

We thank the Animal Resources Center (ARC) husbandry staff at the Health Discovery Building for excellent animal care, and Dr. Laura Fonken for helpful critique and feedback on the manuscript. Partial support was provided by University of Texas at Austin start-up funds (ADG), the Wings for Life Foundation (ADG) and Mission Connect, a program of the TIRR Foundation (ADG)..

Effects of dim light at night in C57BL/6J mice on recovery after spinal cord injury

“…4 ). As previously reported (Gaudet et al, 2017; Lee et al, 2023b), moderate T9 contusion SCI induces post-operative heat hyperalgesia and mechanical allodynia relative to sham surgery. We established that dLAN elicited a decrease in the SUDO threshold in SCI mice at 13 dpo— indicating that dLAN exacerbated SCI-induced mechanical allodynia at that timepoint ( Fig.…”

“…As previously reported (Gaudet et al, 2017;Lee et al, 2023b), moderate T9 contusion SCI induces post-operative heat hyperalgesia and mechanical allodynia relative to sham surgery.…”

“…Testing for neuropathic pain-associated behaviors was performed as previously described (Gaudet et al, 2017, 2021; Lee et al, 2023b). Mice were acclimated to the von Frey and Hargreaves apparatus for two 40-60 min sessions, followed by two pre-surgery tests (average of the two pre-surgery scores are presented here).…”

“…Mice received sham surgery (sham LD: n=6 (4 females and 2 males); sham dLAN: n=7 (3 females and 4 males)) or 65 kDyn T9 contusion SCI (SCI LD: n=10 (5 females and 5 males), force: 67.5 ± 0.9 kDyn; displacement: 532 ± 17 m) (SCI dLAN: n=8 (6 females and 2 males), force: 68.3 ± 0.9 kDyn; displacement: 524 ± 12 m). Mice were prospectively excluded from analysis if the Infinite Horizon force/displacement curves suggested a slip or bone hit; if SCI displacement was 100 m higher or lower than the mean displacement; if mice died during surgery or prior to the experimental endpoint due to ill health/related euthanasia; or if the BMS score was unusually high at 1 dpo (BMS of 3 or greater) (Lee et al, 2023b). 5 male SCI mice were excluded (2 died during surgery, 1 died during bladder care, 1 due to bone hit, 1 due to high 1 dpo BMS score), 2 male sham mice were excluded (died during surgery), and 1 female sham mouse was excluded (died during surgery) (these mice are excluded from the final numbers presented above).…”

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

“…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. By comparing males and females directly, it can be challenging to determine whether observed differences in pain sensitivity or pain-related behaviors are a result of the baseline biological differences or the effects of the treatment or intervention being tested.…”