Gender differences in paclitaxel-induced neuropathic pain behavior and analgesic response in rats

BACKGROUND: Females show greater sensitivity than males to several modalities of experimental pain. However, the gender differences in paclitaxel-induced neuropathic pain have not been studied. The current study examined the gender differences in neuropathic pain behavior and the effect of analgesics in a paclitaxel-induced neuropathic pain model in rats. METHODS: Neuropathic pain was induced by intraperitoneal injection of paclitaxel (2 mg/kg) on 4 alternate days in Sprague-Dawley rats of both genders. Mechanical allodynia was measured using a von Frey filament. The gender differences in analgesic responses were determined after administration of morphine (2 or 5 mg/kg), ketamine (2 or 5 mg/kg), or combined morphine (2 mg/kg) and ketamine (2 mg/kg). RESULTS: Paclitaxel induced mechanical allodynia, which began to manifest on day 4, peaked within 10 days, and plateaued for at least 2 months after the first paclitaxel injection. No gender difference in the manifestation of mechanical allodynia was observed. A 2 mg/kg dose of ketamine increased the mechanical threshold only in males. The 5 mg/kg dose of ketamine significantly increased the mechanical threshold in both genders. Morphine (2 and 5 mg/kg) dose-dependently increased the mechanical thresholds in both genders. The 2 mg/kg dose of ketamine enhanced the antinociceptive effect of 2 mg/kg morphine only in females. CONCLUSIONS: No gender difference in paclitaxel-induced neuropathic pain or analgesic response to ketamine or morphine was observed in Sprague-Dawley rats. Low dose ketamine enhanced the analgesic effect of morphine on paclitaxel-induced mechanical allodynia but only in female rats.