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1 Chung-Shan Medical University
2 China Medical University
* To whom correspondence should be addressed. E-mail: tblin{at}csmu.edu.tw.
Glucose-sensitive neurons in the lateral hypothalamic area produce orexin-A (OxA) as well as orexin-B (OxB) and send their axons to the spinal dorsal horn, which predominantly expresses orexin receptor 1 (OX-1) showing a higher sensitivity to OxA. The purpose of the present study was to assess the effects of OxA on the induction of a novel form of activity-dependent reflex potentiation, spinal reflex potentiation (SRP), in the pelvic-urethral reflex activity. External urethra sphincter electromyogram in response to pelvic afferent nerve test stimulation (TS, 1/30 Hz) or repetitive stimulation (RS, 1 Hz) was recorded in anesthetized rats. TS evoked a baseline reflex activity, whereas RS produced SRP which was abolished by intrathecal OxA (30 nM, 10µL). Intrathecal SB-408124 (10 uM, 10 uL), an OX-1 antagonist, reversed the abolition on SRP caused by OxA. Although there is so far no NR2A and NR2B specific agonist avalible, NMDA reversed the abolition on the RS-induced SRP caused by the co-administration of OxA and Co-101244 (30 nM, 10µL, a NMDA NR2B subunit antagonist) but it did not reverse the abolition by the co-administration of OxA and PPPA (300 nM, 10µL, a NMDA NR2A subunit antagonist). In conclusion, the activation of descending orexinergic fibers may inhibit the repetitive afferent input-induced central sensitization of pelvic-urethral reflex activity and urethra hyperactivity, indicating that spinal orexinergic neural transmission may be a novel target for the treatment of patients with neuropathetic or post-inflammatory pain of pelvic origin.
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