Pain condition and sex differences in the descending noradrenergic system following lateral hypothalamic stimulation

Abstract The lateral hypothalamus (LH) is known to modulate nociception via the descending noradrenergic system in acute nociception, but less is known about its role in neuropathic pain states. In naive females, LH stimulation produces opposing effects of α-adrenoceptors, with α2-adrenoceptors mediating antinociception, while pronociceptive α1-adrenoceptors attenuate the effect. Whether this opposing response is seen in neuropathic conditions or in naive males is unknown. We used a mixed factorial design to compare male and female rats with chronic constriction injury (CCI) to naive rats, measured by Total Paw Withdrawal (TPW) responses to a thermal stimulus. Rats received one of three doses of carbachol to stimulate the LH followed by intrathecal injection of either an α1- or an α2-adrenoceptor antagonist (WB4101 or yohimbine, resp.) or saline for control. Overall, naive rats showed a more pronounced opposing alpha-adrenergic response than CCI rats (p