VAGAL AFFERENT STIMULATION PRODUCED EFFECTS ON NOCICEPTION IN CAPSAICIN-TREATED RATS

1. The effects of electrical stimulation of cervical vagal afferent fi bers on the nociceptive tail-flick (TF) reflex and responses of spinal dorsal horn neurons to noxious cutaneous stimulation were studied in adult rats treated as neonates with either capsaicin or vehicle. 2. Va gal afferent stimulation (VAS) produced biphasic, intensity-dependent effects on the TF reflex in vehicle-treated and untreated control rats . The TF reflex was facilitated in both groups of rats at lesser inten sities of VAS (2.5-50 muA) and fully inhibited at greater intensities of VAS (50-100 muA). In contrast, biphasic effects of VAS on the TF re flex generally were not produced in rats treated as neonates with caps aicin. Facilitation of the TF reflex was produced in these rats by les ser intensities of VAS as well as by typically ''inhibitory'' intensit ies of VAS; the TF reflex was never inhibited in 6/12 rats, even at th e greatest intensity of VAS tested (1,000 muA). When the TF reflex was inhibited by VAS in capsaicin-treated rats, the intensities required were significantly greater than those required in vehicle-treated or u ntreated rats. 3. In electrophysiological experiments, 77 neurons were recorded in the lumbar spinal dorsal horn of pentobarbital sodium-ane sthetized, paralyzed rats treated as neonates with either vehicle or c apsaicin. The neurons had receptive fields on the glabrous skin of the plantar surface of the ipsilateral hind foot, and all responded to me chanical stimuli of both nonnoxious and noxious intensities; 16/77 neu rons also responded to noxious thermal stimulation. In vehicle-treated rats, nociceptive responses of 50% of 30 units studied were biphasica lly modulated by VAS, 33% were only inhibited, and 17% were only facil itated by VAS at the intensities tested (5-500 muA). In capsaicin-trea ted rats, nociceptive responses of 32% of 47 units studied were biphas ically modulated by VAS, 15% were only inhibited, and 34% were only fa cilitated by VAS at the intensities tested (5-500 muA). In addition, n ociceptive responses of neurons facilitated at lesser intensities of V AS and not affected at greater intensities of VAS were observed in cap saicin-treated rats (19% of the 47-unit sample). Overall, the proporti on of the neuronal sample inhibited by VAS was less, and the proportio n of the sample facilitated by VAS was greater in capsaicin-treated ra ts compared with vehicle-treated rats. 4. The efficacy of the capsaici n treatment was evaluated immunocytochemically. In vehicle-treated rat s, substance P (SP) and calcitonin gene-related peptide (CGRP)-like im munoreactivity was localized in axons and terminals densely distribute d in the superficial dorsal horn of the lumbar spinal cord and Lissaue r's tract. SP- and CGRP-like immunoreactivity was also present in the nucleus tractus solitarius and the spinal trigeminal tract. Neonatal t reatment with capsaicin clearly reduced both SP- and CGRP-like immunor eactivity in the spinal cord, spinal trigeminal tract, and the nucleus tractus solitarius. 5. The present results confirm the powerful modul atory effects of cervical VAS on spinal nociceptive reflexes and spina l nociceptive transmission. VAS-produced inhibition of these response measures was selectively attenuated, whereas VAS-produced facilitation was more readily produced in rats treated as neonates with capsaicin. Thus VAS-produced inhibitory effects on spinal nociception likely dep end on capsaicin-sensitive, C-fibers in the vagus nerve, whereas VAS-p roduced facilitatory effects on nociception are independent of these a fferents.