Ventromedial medulla: pain modulation and beyond

Abstract

The midbrain periaqueductal gray (PAG) and ventromedial medulla (VMM) are generally viewed as the core of an endogenous descending modulatory system. However, available data demonstrate that PAG and VMM do not specifically target nociceptive transmission and that activation of either structure affects numerous homeostatic physiological processes. Pseudorabies virus (PRV) is a useful tracer that is retrogradely and transynaptically transported. PRV injections into homeostatic effector organs invariably label VMM neurons, both serotonergic and nonserotonergic. Studies in anesthetized rats have implicated two types of nonserotonergic VMM neurons in nociceptive modulation: ON cells are thought to facilitate nociception and OFF cells to inhibit nociception. Yet, in the unanesthetized animal, the discharge of VMM neurons changes in response to innocuous stimuli and during situations unrelated to nociception. In particular, VMM cells appear to modulate the timing of micturition, with ON cells promoting the initiation of voiding and OFF cells promoting urine storage. VMM cells also modulate sensory transmission. During both micturition and sleep, OFF cells discharge and sensory responsiveness is depressed. In sum, the VMM is hypothesized to modulate spinal sensory, autonomic, and motor circuits in order to maintain homeostasis.