Descending control of nociception: Specificity, recruitment and plasticity

Abstract

The dorsal horn of the spinal cord is the location of the first synapse in pain pathways, and as such, offers a very powerful target for regulation of nociceptive transmission by both local segmental and supraspinal mechanisms. Descending control of spinal nociception originates from many brain regions and plays a critical role in determining the experience of both acute and chronic pain. The earlier concept of descending control as an "analgesia system" is now being replaced with a more nuanced model in which pain input is prioritized relative to other competing behavioral needs and homeostatic demands.Descending control arises from a number of supraspinal sites, including the midline periaqueductral gray-rostral ventromedial medulla (PAG-RVM) system, and the more lateral and caudal dorsal reticular nucleus (DRt) and ventrolateral medulla (VLM). Inhibitory control from the PAG-RVM system preferentially suppresses nociceptive inputs mediated by C-fibers, preserving sensorydiscriminative information conveyed by more rapidly conducting A-fibers. Analysis of the circuitry within the RVM reveals that the neural basis for bidirectional control from the midline system is two populations of neurons, ON-cells and OFF-cells, that are differentially recruited by higher structures important in fear, illness and psychological stress to enhance or inhibit pain. Dynamic shifts in the balance between pain inhibiting and facilitating outflows from the brainstem play a role in setting the gain of nociceptive processing as dictated by behavioral priorities, but are also likely to contribute to pathological pain states.

Nociception and autonomic nervous system

“…Functional neuroimaging studies in humans indicate that PAG activation by nociceptive inputs is modulated by attention, emotion, expectation of pain and expectation-related placebo analgesia [54][55][56][57][58][59][60][61]. Experimental studies using chemical microstimulation indicate that the different columns of the PAG organize different coping strategies to pain and other stressors [62][63][64][65][66]. The lateral and dorsolateral PAG initiate flight or fight responses associated with tachycardia, hypertension, and redistribution of blood flow, i.e., sympathoexcitatory responses mediated by neurons of the ventrolateral medulla (VLM), which activate sympathetic preganglionic neurons controlling cardiovascular effectors [65][66][67][68].…”

“…PAG is a critical component of the pain modulation network that exerts a dual control, inhibitory or excitatory, on nociceptive transmission in the dorsal horn and trigeminal nucleus. The balance between inhibition and facilitation of nociception is dynamic and can be altered in different behavioral, emotional, and pathologic states [63,69]. The PAG exerts its pain modulatory effects primarily via its descending projection to the rostral VM (RVM).…”

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

“…The limbic system mediates the emotional and motivation-related aspects of nociception, while the somatosensory cortex is mainly responsible for pain differentiation and localization (Apkarian et al 2005 ) . Additional pathways descending from a handful of brain regions, including the periaqueductal gray, rostroventromedial medulla, lateral reticular nucleus, and some brainstem monoamine cell groups, modulate nociception (Heinricher et al 2009 ) .…”

Nociceptors: the sensors of the pain pathway

“…The relay neurons project to the medulla, mesencephalon, and thalamus, which in turn project to somatosensory and anterior cingulate cortices to drive sensory-discriminative and affective-cognitive aspects of pain, respectively (38). Local inhibitory and excitatory interneurons in the dorsal horn as well as descending inhibitory and facilitatory pathways originating in the brain modulate the transmission of nociceptive signals, thus contributing to the prioritization of pain perception relative to other competing behavioral needs and homeostatic demands (39).…”