Central mechanisms of pain suppression

In contrast to a classic view that the brain was a passive receiver of the pain message, Melzack and Wall proposed in 1965 that the brain exerted descending control upon spinal nociceptive transmission. This chapter reviews the substrates mediating endogenous pain-modulation. The respective roles of the ventrolateral periaqueductal gray (vlPAG) and rostroventromedial medualla (RVM) in the mediation of not only pain-inhibitory, but also pain-facilitatory responses are described behaviorally, neuroanatomically, neurochemically and neurophysiologically. How this intrinsic pain-modulatory system is activated by other brain nuclei (limbic system and cortex) and by exogeneous environmental factors is described. The emergence of sex differences and neurohormonal factors in mediating pain modulation is also considered. The neurophysiological underpinnings of RVM "ON-" and "OFF-cells" and their respective roles in endogenous pain-facilitatory and pain-inhibitory responses are discussed in detail. Finally, how these pain-modulatory responses relate to other neurobehavioral adapatations are considered, including how animal studies can inform human pain conditions and their detection through functional imaging.