Sex-related analgesic responses to photobiomodulation therapy in rats with neuropathic pain

Abstract Neuropathic pain is associated with sensory abnormalities and remains difficult to treat. Photobiomodulation therapy (PBMT) has emerged as a non-pharmacological approach with analgesic potential; however, sex-related differences in treatment responses remain poorly understood. We investigated the effects of PBMT in male and female rats subjected to chronic constriction injury (CCI) of the sciatic nerve. Animals received infrared PBMT administered three times per week during ten sessions, and nociceptive responses were assessed using mechanical hyperalgesia and tactile allodynia throughout treatment. CCI induced significant nociceptive hypersensitivity in both sexes. PBMT progressively increased withdrawal thresholds and reduced pain-like behaviors. Females exhibited greater relative recovery in both mechanical hyperalgesia and tactile allodynia, whereas males maintained higher absolute nociceptive thresholds throughout the experimental period. Estrous cycle analysis revealed reduced pain sensitivity during metestrus compared with estrus and proestrus. These findings demonstrate that PBMT effectively attenuates neuropathic pain-like behaviors in both sexes and suggest that biological sex and hormonal status may influence therapeutic responses. The results support the inclusion of sex as a biological variable in preclinical photobiomodulation studies.