Effects of progesterone on neuropathic pain responses in an experimental animal model for peripheral neuropathy in the rat: A behavioral and electrophysiological study

Progesterone (PROG) is promising as an important protective agent against various injuries to the nervous system. The present study was designed to investigate whether starting PROG administration, when symptomatology is already established, would alleviate the expression of nociceptive behaviors (mechanical allodynia and thermal hyperalgesia) and electrophysiological changes in a chronic constriction injury (CCI) model of neuropathic pain in rats. Male rats were given PROG (1.5, 3, 6 and 12 mg/kg, i.p.) 12 days after CCI induction, and dosing continued daily until day 26. Behavioral tests were done immediately before surgery (day 0) and on days 12, 26, 28, and 35 post-CCI, and were followed by electrophysiological measurements in the last day. PROG at doses of 6 or 12 mg/kg reduced both the thermal hyperalgesia and mechanical allodynia induced by CCI. Electrophysiological data indicated that CCI-induced animals had a remarkable decrement of both compound muscle and nerve action potential amplitudes recorded in the gastrocnemius muscle and sural nerve, respectively. CCI also caused a significant reduction in motor and sensory conduction velocities measured in the sural and tibial nerves, respectively. PROG at doses of 6 or 12 mg/kg induced a significant recovery of all electrophysiological changes. Our data indicated that starting PROG therapy when symptomatology is already established, and continuing it for a sufficient period of time, may have a therapeutic effect. This suggests that PROG may offer new strategies for the treatment of neuropathic pain.