Sex-related correspondence between mechanical hypersensitivity and the discharge of medullary pain control neurons in neuropathic rats

Abstract

Here we studied whether the sex-related difference in mechanical hypersensitivity induced by neuropathy is associated with the discharge rate of medullary pain control neurons. We performed experiments in male and female rats with spared nerve injury (SNI) model of peripheral neuropathy. Mechanical hypersensitivity was assessed behaviorally by monofilaments. Discharge rates of pain-control neurons were determined using in vivo single unit recordings under light anesthesia. Recording targets were two medullary nuclei involved in descending pain control: the rostral ventromedial medulla (RVM) and the medullary dorsal reticular nucleus (DRt). Based on the response to peripheral noxious stimulus, neurons were classified as pronociceptive RVM ON-like or DRt neurons, or antinociceptive RVM OFF-like neurons. Behavioral results indicated that the mechanical hypersensitivity induced by SNI was significantly stronger in females than males. The ongoing discharge rates of pronociceptive RVM ON-like neurons were higher and those of antinociceptive RVM OFF-like neurons lower in SNI females than SNI males. Ongoing discharge rates of pronociceptive DRt neurons were not significantly different between SNI females and males. The results suggest that a sex difference in the discharge rate of pain control neurons in the RVM but not DRt may contribute to the maintenance of stronger neuropathic hypersensitivity in females.