Descending control of nociception.. 많이 찾았다.

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Descending control of spinal nociceptive transmission.pdf

Afferent pain pathways 2004 review.pdf

descending control of pain.pdf

short term synaptic plasticity in the nociceptive thalamic .pdf

Descending control of nociception: Specificity, recruitment and plasticity

Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA. heinricm@ohsu.edu

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 periaqueductal 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 sensory-discriminative 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.

Descending control of spinal nociception from the periaqueductal grey distinguishes between neurons with and without C-fibre inputs.

Waters AJ, Lumb BM.

Department of Physiology, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.

Abstract

Information about noxious events in the periphery is conveyed to the spinal cord in A- and C-fibre nociceptive afferents, which have largely distinct electrical and chemical properties and which convey different qualities of the pain signal. Descending control that originates in the different functional columns of the midbrain periaqueductal grey (PAG) has important roles in the modulation of spinal nociception in different behavioural and emotional states and, it is now believed, in animal models of chronic pain. However, few studies of descending control have considered differential modulation of A- versus C-nociceptor-evoked responses. Here, we report that descending inhibitory control from the rostrocaudal extent of the dorsolateral/lateral and ventrolateral columns of the PAG preferentially targets Class 2 deep dorsal horn neurons with C-fibre inputs. Pinch-evoked responses of these neurons were depressed significantly by -37+/-4.2% (P<0.0001). In contrast, the pinch-evoked responses of Class 2 neurons without C-fibre inputs (presumably A-fibre mediated) were enhanced significantly by +34+/-11.8% (P<0.01). Further experiments indicated these facilitatory effects were at least partly due to a reduction in C-fibre-mediated segmental inhibition. We suggest this differential control of spinal nociception would be appropriate in many of the varied situations in which the PAG is believed to become active, whether short term (e.g. fight or flight) or long term (e.g. chronic pain). Additionally, the pro-nociceptive effects observed in a subset of spinal neurons may be related to the descending facilitation that has been reported in animal models of chronic pain.

To the descending pain-control system in rats, inflammation-induced primary and secondary hyperalgesia are two different things.

Vanegas H.

Instituto Venezolano de Investigaciones Cientificas (IVIC), Apartado 21827, Caracas 1020A, Venezuela. hvanegas@ivic.ve

Abstract

The periaqueductal gray matter and the rostral ventromedial medulla (RVM), with its projections to the spinal dorsal horn, constitute the efferent channel of the 'descending pain-control system'. Noxious stimulation of a peripheral tissue causes more pain if this tissue is inflamed (primary hyperalgesia). In such cases, stimulation of neighboring but uninflamed tissues also becomes more painful (secondary hyperalgesia). In animal models of inflammation, the descending pain-control system sends down, simultaneously, inhibitory and facilitatory influences, but inhibition predominates for primary hyperalgesia while facilitation predominates for secondary hyperalgesia. Descending inhibition and facilitation during peripheral inflammation are due not only to previously existing descending modulation, but also to inflammation-induced changes in RVM which involve receptors for NMDA, AMPA, cholecystokinin and neurotensin, as well as synthesis of enkephalins and nitric oxide.

Deconstructing endogenous pain modulations.

Mason P.

Department of Neurobiology, Pharmacology and Physiology, University of Chicago, MC 0926, 947 East 58th St., Chicago, IL 60637, USA. p-mason@uchicago.edu

Abstract

A pathway from the midbrain periaqueductal gray (PAG) through the ventromedial medulla (VMM) to the dorsal horn constitutes a putative endogenous nociceptive modulatory system. Yet activation of neurons in both PAG and VMM changes the responses of dorsal horn cells to non-noxious stimuli and elicits motor and autonomic reactions that are not directly related to nociception. Activation of mu-opioid receptors in VMM and PAG also modifies processes in addition to nociceptive transmission. The descending projections of VMM neurons are not specific to nociception as VMM projects to the spinal superficial dorsal horn where thermoreceptors as well as nociceptors terminate. In addition, experiments with pseudorabies virus demonstrate multi-synaptic pathways from VMM to sympathetic and parasympathetic target organs. VMM neurons respond to both noxious and unexpected innocuous stimuli of multiple modalities, and change their discharge during behaviors unrelated to pain such as micturition/continence and sleep/wake. In conclusion, all available evidence argues against the idea that PAG and VMM target nociception alone. Instead these brain stem sites may effect homeostatic adjustments made necessary by salient situations including but not limited to injury.

Ventromedial medulla: pain modulation and beyond.

Mason P.

Department of Neurobiology, Pharmacology & Physiology and Committee on Neurobiology, University of Chicago, Chicago, Illinois 60637, USA. p-mason@uchicago.edu

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. (c) 2005 Wiley-Liss, Inc.