Short communication Efficacy of nociceptin inhibition on WDR neuron activity is enhanced in mononeuropathic rats Maria Luisa Sotgiu * , Paola Bellomi, Gabriele E.M. Biella Istituto Bioimmagini e Fisiologia Molecolare, CNR, Via Fratelli Cervi 93, 20090 Segrate (Mi), Italy Accepted 19 November 2003 Abstract Nociceptin (NC), administered microiontophoretically at different concentrations, significantly reduced the spontaneous and stimulus- evoked activity on WDR neuron in rats with chronic constriction of one sciatic nerve and showing signs of neuropathic pain. The effect was not antagonized by Naloxone. The same concentrations of NC were ineffective on the noxious stimulus evoked responses of WDR neurons in sham and intact rats. This result indicates a facilitated inhibitory action of NC on nociceptive transmission in this pain model. D 2003 Elsevier B.V. All rights reserved. Keywords: Nociceptin; Wide dynamic range neuron; Noxious evoked activity; CCI rat Nociceptin (NC)/orphanin FQ is a widely distributed endogenous peptide that plays a role in a variety of functions [12,13]. Physiological and behavioral evidence indicates the dual involvement of NC in the modulation of nociception, with a prevailing inhibitory effect at the spinal cord level [11,15,16]. Intrathecal NC has been shown to produce an analgesic effect on different animal models of pain [9,20]. In the neuropathic pain model, abnormal signs of pain like sponta- neous pain and hyperalgesia have been associated with altered activity in wide dynamic range (WDR) neurons [17]. We investigated the potential effects of NC on this altered activity. In rats with behavioral signs of neuropathic pain we applied, microiontophoretically, different concentrations of NC, continuously recording the spontaneous and stimulus- evoked activities of WDR neurons. Fifteen adult male Sprague – Dawley rats in the study underwent, under deep anesthesia (Nembutal 50 mg/kg) and in aseptic conditions, a unilateral sciatic nerve constriction (11 rats) according to Bennett and Xie [1], or a sham operation without constriction (4 rats). Before surgery and prior to the electrophysiological experiments we evaluated thermal and mechanical reflexes by (1) the hot-plate test (52 jC), measuring the paw licking latency (PLL in s), and (2) the von Frey calibrated filaments, measuring the withdrawal threshold (WT in g). The values on the injured paw lower than those before surgery were taken as the indexes of thermal and mechanical hyper- algesia, respectively. For the electrophysiological experiments, performed 2 weeks after surgery, the rats were anesthetized with Nem- butal (40 mg/kg i.p. for induction, 10 mg/kg i.v. for maintenance) and paralyzed with gallamine triethiodide (20 mg/kg/h). After cannulation of the jugular vein, one common carotid artery and the trachea, the rats were mounted in a metal frame where they underwent a lam- inectomy from L1 to S1. Body temperature, arterial blood pressure and heart rate were monitored continuously. The stability of the arterial pressure (values of 90–110 mmHg) and heart rate (values of 320 F 10 beats/min) signalled adequate anesthesia. A seven-barrelled glass micro-pipette (home-made) was positioned, under a dissecting micro- scope, on the surface of the spinal cord ipsilateral to the constriction, or to the sham surgery, and advanced at 2-Am steps. Extracellular activity was recorded using the central barrel filled with 3 M NaCl. The depth of the neurons was taken from the mean microdrive readings of descent and on returning to the cord surface. The iontophoretic barrels were filled with nociceptin (NC: 1, 2, and 2.5 mM, pH 5.5), naloxone (nalo 5 mM, pH 5.0), the vehicle and saline for the automatic neutrali- zation of tip currents. Small retention currents (2–5 nA) were used to avoid leakage, by diffusion, of the active substances. Substances, 0006-8993/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.brainres.2003.11.025 * Corresponding author. Tel.: +39-21717530; fax: +39-21717558. E-mail address: maria.luisa.sotgiu@ibfm.cnr.it (M.L. Sotgiu). www.elsevier.com/locate/brainres Brain Research 998 (2004) 251 – 254