LOCUS-COERULEUS MODULATES THALAMIC NOCICEPTIVE RESPONSES VIA ADRENOCEPTORS

This study investigated the parafascicular (PF) neuronal nociceptive r esponses and their modulation following electrical stimulation of the locus coeruleus (LC) and intrathecal (i.t.) or intracerebroventricular (i.c.v.) administration of two ol-adrenoceptor antagonists, the alpha (2)-antagonist, yohimbine, and the alpha(1)-antagonist, prazosin. The main results were as follows: (1) the nociceptive evoked discharges in PF neurons were suppressed by preceding stimulation of LC; (2) the su ppressive effect of LC stimulation on PF neurons was replaced by a fac ilitatory effect following pretreatment of i.t. yohimbine in 14 units tested, while i.t. prazosin failed to alter the LC-induced suppression , even when the prazosin dose was doubled; (3) i.c.v. pretreatment wit h prazosin strengthened the suppressive effect of LC stimulation on PF neurons; (4) i.c.v. norepinephrine (NE) administration induced, in PF neurons, a biphasic response to noxious stimulation; an early, brief (about 10 min) inhibitory effect followed by a late, long-lasting faci litatory effect; and (5) i.c.v. pretreatment of yohimbine or prazosin prevented the inhibitory or facilitatory responses released by NE, res pectively. These results provide evidence that: (1) the LC-descending projections exhibit a suppressive effect on nociceptive transmission a t the spinal level through alpha(2)-receptors; and (2) the LC-ascendin g projections exhibit dual effects, facilitatory and inhibitory, at th e medial thalamus (PF) level through alpha(1)- and alpha(2)-receptors, respectively. (C) 1998 Elsevier Science B.V.