Circuitry and plasticity of the dorsal horn – Toward a better understanding of neuropathic pain. (6th August 2015)

• Record Type: Journal Article
• Authors: West, S.J.; Bannister, K.; Dickenson, A.H.; Bennett, D.L.
• Is Part Of: Neuroscience. Volume 300(2015)
• Page Start: 254
• Page End: 275
• Publication Date: 2015-08-06
• Subjects: 5HT 5-hydroxytryptamine -- AMPA alpha-amino3-hydroxy-5-methyl-4-isoxazoleproprionic acid -- BDNF brain-derived neurotrophic factor -- CGRP calcitonin gene related peptide -- CVLM caudal ventrolateral medulla -- DH dorsal horn -- DRG dorsal root ganglion -- GABA gamma-aminobutyric acid -- GAD(65) glutamic acid decarboxylase (65) -- IB4 isolectin B4 -- KCC2 potassium-chloride cotransporter 2 -- LC locus coeruleus -- LTP long-term potentiation -- mGlu metabotropic glutamate receptor -- NA noradrenaline -- NGF nerve growth factor -- NK-1 neurokinin 1 -- NKCC1 sodium-potassium-chloride cotransporter 1 -- NMDA N-methyl-d-aspartate receptors -- NS nociceptive specific -- PAD primary afferent depolarization -- PAG periaqueductal gray -- PKCγ protein kinase C gamma -- RVM rostral ventromedial medulla -- WDR wide dynamic range neurons; neuropathic pain -- plasticity -- dorsal horn -- descending control -- primary afferent; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.05.020
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: We review the contribution of plasticity in the dorsal horn to hypersensitivity following peripheral nerve injury. Primary afferent neurons show spontaneous activity, phenotypic changes, and altered connectivity. Dorsal horn neurons undergo activity-dependent plasticity, and show altered expression patterns and connectivity. Descending controls to the dorsal horn are modulated which help to drive the neuropathic phenotype. Abstract: Maladaptive plasticity within the dorsal horn (DH) of the spinal cord is a key substrate for development of neuropathic pain following peripheral nerve injury. Advances in genetic engineering, tracing techniques and opto-genetics are leading to a much better understanding of the complex circuitry of the spinal DH and the radical changes evoked in such circuitry by nerve injury. These changes can be viewed at multiple levels including: synaptic remodeling including enhanced excitatory and reduced inhibitory drive, morphological and electrophysiological changes which are observed both to primary afferent inputs as well as DH neurons, and ultimately circuit-level rewiring which leads to altered connectivity and aberrant processing of sensory inputs in the DH. The DH should not be seen in isolation but is subject to important descending modulation from the brainstem, which is further dysregulated by nerve injury. Understanding which changes relate to specific disease-states is essential, and recent work has aimed to stratify patient populations in a mechanistic fashion. In this review we will discuss how such pathophysiological mechanisms may lead to the distressing sensory phenomena experienced by patients suffering neuropathic pain, and the relationship of such mechanisms to current and potential future treatment modalities.