The caudal ventrolateral medulla as an important inhibitory modulator of pain transmission in the spinal cord

Abstract

The caudal ventrolateral medulla (VLM) has emerged during the last decade as one of the main components of the endogenous pain control system. Profound and long-lasting analgesia is produced by mild stimulation of the VLM. The VLMlat, the reticular formation located between the spinal trigeminal nucleus and the lateral reticular nucleus (LRt), appears to play a major role in that antinociceptive action. The projections to spinal cord laminae involved in nociceptive transmission originate exclusively in the VLMlat. The VLMlat participates in a disynaptic pathway involving spinally projecting pontine A5 noradrenergic neurons, which appears to convey α2-adrenoreceptor-mediated analgesia produced from the VLM. Neurons in the VLMlat and in lamina I are reciprocally connected by a closed loop that is likely to mediate feedback control of supraspinal nociceptive transmission. On the other hand, the LRt, which is targeted by ventral (lamina VII) and deep dorsal (laminae IV to V) horn inputs, projects to the premotor lamina VII. Nociceptive input ascending from the cord and increases in blood pressure are discussed as possible physiologic triggers of the analgesia produced by the VLM. The overall role of the VLM as a center for integration of nociceptive, cardiovascular, and motor functions is discussed. The putative therapeutic benefits of manipulating the VLM for the control of chronic pain are envisaged. © 2002 by the American Pain Society