Abstract:
There are sex differences in the sensory experience of pain. For example, the incidence of chronic pain syndromes is higher in women than in men. Studies of gonadal steroid modulation of pain have, to date, focused on the activational effects of estrogen in adult females. However, little is known about the activational effects of male gonadal hormones on nociception. We hypothesize that endogenous testosterone and/or its metabolites, dihydrotestosterone (DHT) or estrogen, have an activational effect on nociception in males. To determine the specific contribution of male gonadal hormones to sex differences in pain sensation, gonadectomized (GDX) or intact control male rats were evaluated for nociceptive behaviors in three models of pain: acute thermal or mechanical, persistent inflammatory, or chronic neuropathic injury. Using a thermal analgesiometer and von Frey monofilaments, there was no significant difference between GDX and naïve rats for acute thermal or mechanical nociceptive hind paw withdrawal thresholds. However, following subcutaneous injection of formalin into the hind paw as a persistent inflammatory stimulus, naïve rats showed significantly more hind limb flinches than GDX rats. Following unilateral spared nerve injury (SNI) as a chronic pain model, mechanical withdrawal thresholds of the contralateral paw were significantly higher in sham-GDX (intact) rats than GDX rats. The results from these specific pain models suggest that endogenous male gonadal hormones may have complex modulatory effects in persistent or chronic, but not acute pain states.