Differential gene expression in trigeminal ganglia of male and female rats following chronic constriction of the infraorbital nerve.

BACKGROUND: The mechanisms underlying sex-based differences in pain and analgesia are poorly understood. In this study, we investigated gene expression changes in trigeminal ganglia (TG) of male and female rats exposed to infraorbital nerve chronic constriction injury (IoN-CCI). METHODS: Somatosensory assessments were performed prior to IoN-CCI and at selected time points postsurgery. Selected gene expression changes were examined with real-time quantitative polymerase chain reaction (RT-PCR) in ipsilateral TG at 21 days postsurgery. RESULTS: Rats exposed to IoN-CCI developed significant mechanical allodynia and hyperalgesia on days 19 and 21 postsurgery. During this period, females developed significantly more allodynia but not hyperalgesia compared to males. At 21 days postsurgery, expression levels of 44 of the 84 investigated pain-related genes in ipsilateral TG were significantly regulated relative to naïve rats in either sex. Csf1 and Cx3cr1 were up-regulated in both sexes, but the magnitude of regulation was significantly higher in females (p = 0.02 and p = 0.001, respectively). Htr1a and Scn9a were down-regulated in both sexes, but the down-regulation was significantly more pronounced in males (p = 0.04 and p = 0.02, respectively). Additionally, Cck, Il1a, Pla2g1b and Tnf genes were significantly regulated in females but not in males, and Chrna4 gene was significantly down-regulated in males but not in females. CONCLUSIONS: Our findings suggest sex-dependent gene regulation in response to nerve injury, which may contribute to sex dimorphism of trigeminal neuropathic pain. Further studies are needed to establish gene expression changes over time and correlate these with hormonal and other physiological parameters in male and female. SIGNIFICANCE: We present novel sex-specific transcriptional regulation in trigeminal ganglia that may contribute to male-/female-based differences in trigeminal neuropathic pain. These findings are expected to open new research horizons, particularly in male versus female targeted therapeutic regimens.