The early representation of the pain system was composed of a lateral and a medial ascending spinal pathway, which were involved in the discriminative and motivational– aversive aspects of pain processing, respectively (Melzack & Casey, 1968). This gave rise to a more elaborate concept in which a complex network of largely interconnected ascending and descending pathways distributed nociceptive information through many functionally distinct brain areas (reviewed by Lima, 1997). Accordingly, the so-called ‘supraspinal pain control system’ has recently been considered as an integrator system that dynamically adjusts pain processing and multiple brain functions in a bi- directional manner, rather than a system merely dedicated to pain modulation (Lima, 1997). Among the various pain control centres there are several engaged in autonomic processing, and in particular, cardiovascular control (Lovick, 1991). The demonstration of spinal nociceptive afferent pathways to these areas has been commonly interpreted as the anatomical basis for the well-known cardiovascular reactions to pain (Shapiro, 1961; Abram et al. 1983). However, evidence that variations in cardiovascular parameters can lead to changes in pain perception has been presented more recently (reviewed by Randich & Maixner, 1984; Zamir & Maixner, 1986). In other words, these areas may alter their nociceptive processing secondary to changes in cardiovascular function. Experimental studies aimed at demonstrating that these pain control centres mediate nociceptive–cardiovascular Physiological Society Symposium Nociceptors as Homeostatic Afferents: Central Processing The caudal medullary ventrolateral reticular formation in nociceptive–cardiovascular integration. An experimental study in the rat Deolinda Lima *†‡, António Albino-Teixeira †§ and Isaura Tavares *† * Instituto de Histologia e Embriologia, § Instituto de Farmacologia e Terapêutica da Faculdade de Medicina and † IBMC, Universidade do Porto, Al. Hernani Monteiro, 4200-319, Porto, Portugal The endogenous pain control system is composed of multiple functionally distinct brain regions, which are thought to integrate nociceptive information with various brain functions. The clear involvement of some pain control centres in cardiovascular modulation has been claimed as a strong indication of their role in nociceptive–cardiovascular integration. Particular emphasis has been given to their putative function in triggering cardiovascular reactions to pain. However, the possibility of their participation in the less-studied influence of cardiovascular conditions in pain perception has been largely ignored. We have recently addressed this issue by investigating the involvement of the caudal ventrolateral medullary reticular formation (cVLM) in hypertension-induced hypoalgesia. Circuits capable of conveying cVLM-elicited antinociception include a direct reciprocal cVLM–spinal loop, and two disynaptic spinal pathways relaying in rostroventromedial medullary (RVM) neurones and A 5 noradrenergic neurones. In the three pathways, the cVLM neurones involved are circumscribed to a small area of reticular formation located laterally to the lateral reticular nucleus, the VLMlat. The VLMlat has a vasodepressor effect similar to that obtained from the cVLM. In the spinal cord dorsal horn, c-fos expression evoked by noxious stimuli is decreased in hypertensive animals, as compared to normotensive animals. In hypertensive animals following lesion of the VLMlat, spinal c-fos expression is identical to that observed in normotensive animals. The collected data point to a role for the VLMlat in the depression of spinal nociceptive processing in response to rises in blood pressure. Since hypertension-induced hypoalgesia is mediated by spinal a 2 -adrenoreceptors, this effect could be conveyed by the cVLM–A 5 –spinal pathway. Experimental Physiology (2002) 87.2, 267–274. 2354 Presented at a scientific meeting of the Physiological Society at the University of Bristol in September 2001. Publication of The Physiological Society ‡ Corresponding author: limad@med.up.pt ) by guest on July 13, 2011 ep.physoc.org Downloaded from Exp Physiol (