Orphanin FQ produces gender-specific modulation of trigeminal nociception:Behavioral and electrophysiological observations

The present study aimed to determine if orphanin FQ, an endogenous ligand f or the opioid receptor like-1 receptor, produces gender-specific effects in the modulation of AF-methyl-D-aspartate (NMDA)-evoked responses of trigemi nal nociceptive neurons, and in the NMDA-induced nociceptive behavior. Sing le-unit extracellular recordings were made from nociceptive-specific and wi de dynamic range neurons in the superficial and deeper dorsal horn of the m edulla (trigeminal nucleus caudalis) in anesthetized (1.5 g/kg urethane) ra ts. In the proestrous female, orphanin FQ applied microiontophoretically pr oduced facilitation of the NMDA-evoked responses in 50% (16/32) of nocicept ive neurons, inhibition in 31% (10/32), and biphasic effects in 19% (6/32). In contrast, in the male, it inhibited the responses in 86% (18/21), and f acilitated the responses in 14% (4121). In ovariectomized animals, orphanin FQ inhibited the responses in 75% (9/12) of nociceptive neurons, facilitat ed the responses in 17% (2/12) and produced biphasic effects in 8% (1/12). In contrast, in estradiol-treated ovariectomized rats, it facilitated the r esponses in 46% (5/11), inhibited the responses in 36% (4/11) and produced biphasic effects in 18% (2/11). For behavioral studies, NMDA-induced scratching behavior was used to assess the effects of orphanin FQ. Twenty-eight male, ovariectomized and estradio l-treated ovariectomized rats were microinjected with NMDA (2 nmol in 10 Ll ) alone through a cannula implanted in the medullary region, while another 27 rats were microinjected with orphanin FQ (10 nmol in 10 mul) 10 min prio r to giving NMDA. Orphanin FQ reduced the NMDA-induced nociceptive scratchi ng behavior by 92% in the male, and by 96% in ovariectomized rats. In contr ast, in estradiol-treated ovariectomized animals, orphanin FQ facilitated t he NMDA-induced scratching behavior by 210%. We conclude from these studies that orphanin FQ is primarily pronociceptive in the female and primarily antinociceptive in the male. Furthermore, we s uggest that estrogen is involved in generating the gender-specific effects of orphanin FQ. (C) 2001 IBRO. Published by Elsevier Science Ltd. All right s reserved.