RNA-Seq Reveals Sex Differences in Gene Expression during Peripheral Neuropathic Inflammation and in Pain Relief from a COX-2 Inhibiting Theranostic Nanoemulsion

• Published in: International journal of molecular sciences Vol. 24; no. 11; p. 9163
• Main Authors: Deal, Brooke, Phillips, Katherine, Crelli, Caitlin, Janjic, Jelena M, Pollock, John A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23-05-2023; MDPI
• Subjects: Activating transcription factor 3; Analysis; Animals; ATF3; Biology; Care and treatment; celecoxib; COX-2 inhibitor; COX-2 inhibitors; Dorsal root ganglia; Drug dosages; Drug withdrawal; Females; Gender differences; Gene expression; Genes; Inflammation; Males; Nanoemulsions; neuroinflammation; Pain; Pain perception; RNA; RNA sequencing; RNA-seq; Sciatic nerve; Sex differences; Sexes; Sexual dimorphism; Surgery; Massachusetts; Germany; rat CCI; COX-2 inhibitor; RNA-seq; celecoxib; neuroinflammation; transcriptome; nanoemulsion; nanotheranostic; ATF3; sex differences
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24119163

Given decades of neuroinflammatory pain research focused only on males, there is an urgent need to better understand neuroinflammatory pain in females. This, paired with the fact that currently there is no long-term effective treatment for neuropathic pain furthers the need to evaluate how neuropathic pain develops in both sexes and how it can be relieved. Here we show that chronic constriction injury of the sciatic nerve caused comparable levels of mechanical allodynia in both sexes. Using a COX-2 inhibiting theranostic nanoemulsion with increased drug loading, both sexes achieved similar reduction in mechanical hypersensitivity. Given that both sexes have improved pain behavior, we specifically explored differential gene expression between sexes in the dorsal root ganglia (DRG) during pain and relief. Total RNA from the DRG revealed a sexually dimorphic expression for injury and relief caused by COX-2 inhibition. Of note, both males and females experience increased expression of
(
), however, only the female DRG shows decreased expression following drug treatment. Alternatively,
and
expression appear to play a sex specific role in relief in males. The sex differences in RNA expression reveal that comparable behavior does not necessitate the same gene expression.