Anti-nociceptive Mechanisms of Testosterone in Unilateral Sciatic Nerve Ligated Male Rat

Neuropathic pain is a chronic condition which is mediated by complex mechanisms exerted by the release of nerve neurotransmitter. A correlation exists between the sex hormones and neuropathic pain, however many aspects of this correlation still remain unclear.

The aim of the current study was to determine the anti-nociceptive activity of testosterone and its interaction with the opioidergic, GABAergic, and dopaminergic receptors in sciatic nerve-ligated male rats.

In this study, 170 adult male rats were randomly allocated into the 4 experimental groups following the sciatic nerve ligation. In the experimental group 1, the animals were injected intraperitoneally (i.p.) with saline, testosterone (10 and 15 mg/kg), and morphine (5 mg/kg), and 30 minutes later with formalin into the plantar surface of the right paw. In the experimental group 2, the animals were injected with saline, testosterone (15 mg/kg), nalox-one (2 mg/kg), and testosterone (15 mg/kg)+naloxone (2 mg/kg). In the groups 3 and 4, flumazenil (5 mg/kg) and yohimbine (2 mg/kg) were injected instead of naloxone. Then, the time spent for paw licking was monitored for the first and second phases after the formalin injection.

According to the results, the injection of testosterone in a dose dependent manner decreased the time of licking and biting in the injected paw compared to the control group (P<0.05). Likewise, pretreatment with na-loxone or flumazenil significantly decreased the anti-nociceptive effect of testosterone (P<0.05). While pretreatment with yohimbine significantly increased the anti-nociceptive effect of testosterone (P<0.05).

These results suggested testosterone has an anti-nociceptive activity and this effect is mediated by the opioidergic, GABAergic, and dopaminergic receptors in the sciatic nerve-ligated male rat.