Influence of sex and gonadal hormones on pain perception in a neuropathic pain model in old rats.

Despite growing evidence that nociceptive stimuli are processed and modulated by distinct neural mechanisms depending on biological sex and aging, these factors remain underrepresented in experimental and clinical pain research. Most preclinical studies continue to rely on young male rodents, overlooking potential differences in neuropathic pain perception between sexes and age groups. Understanding these variations is critical for advancing pain management strategies. Aged rats (22 months old) of both sexes were divided into three groups: orchiectomized (Orch) males, non-orchiectomized (Non-orch) males, and females. The animals underwent L5 spinal nerve ligation and were assessed for mechanical allodynia on the plantar surface of their left hind paw before nerve ligation and on days 7, 14, 21, and 28 post-ligation. By day 14, Non-orch males showed a significantly higher withdrawal threshold than Orch males, with an average difference of 8.46 g (P<0.005), which remained significant and increased over time, peaking at day 28, with 13.07 g (P<0.0006). By day 28, Non-orch males also showed greater mechanical allodynia than females, with an estimated mean difference of approximately 8 g (P=0.038). These findings suggest that male gonadal hormones mitigate neuropathic pain-induced mechanical allodynia. The study underscores the role of testosterone in pain modulation and highlights the need for further research on the interplay between hormonal regulation, aging, and neuropathic pain mechanisms.