Chloride regulation in the pain pathway

Theodore J Price; Fernando Cervero; Michael S Gold; Donna L Hammond; Steven A Prescott

doi:10.1016/j.brainresrev.2008.12.015

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Journal article

Peer reviewed

Chloride regulation in the pain pathway

Theodore J Price, Fernando Cervero, Michael S Gold, Donna L Hammond and Steven A Prescott

Brain Research Reviews, Vol.60(1), pp.149-170

2009

DOI: 10.1016/j.brainresrev.2008.12.015

PMCID: PMC2903433

PMID: 19167425

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Abstract

Melzack and Wall's Gate Control Theory of Pain laid the theoretical groundwork for a role of spinal inhibition in endogenous pain control. While the Gate Control Theory was based on the notion that spinal inhibition is dynamically regulated, mechanisms underlying the regulation of inhibition have turned out to be far more complex than Melzack and Wall could have ever imagined. Recent evidence indicates that an exquisitely sensitive form of regulation involves changes in anion equilibrium potential ( E anion), which subsequently impacts fast synaptic inhibition mediated by GABA A, and to a lesser extent, glycine receptor activation, the prototypic ligand gated anion channels. The cation-chloride co-transporters (in particular NKCC1 and KCC2) have emerged as proteins that play a critical role in the dynamic regulation of E anion which in turn appears to play a critical role in hyperalgesia and allodynia following peripheral inflammation or nerve injury. This review summarizes the current state of knowledge in this area with particular attention to how such findings relate to endogenous mechanisms of hyperalgesia and allodynia and potential applications for therapeutics based on modulation of intracellular Cl − gradients or pharmacological interventions targeting GABA A receptors.

Disinhibition

NKCC1

Cation-chloride cotransporters

KCC2

Inflammatory pain

Neuropathic pain

Details

Title: Subtitle: Chloride regulation in the pain pathway
Creators: Theodore J Price - University of Arizona, Department of Pharmacology, USA
Fernando Cervero - McGill University, Department of Anesthesia, McGill Centre for Research on Pain, Canada
Michael S Gold - University of Pittsburgh, Department of Medicine, USA
Donna L Hammond - University of Iowa, Department of Anesthesia, USA
Steven A Prescott - University of Pittsburgh, Department of Neurobiology, USA
Resource Type: Journal article
Publication Details: Brain Research Reviews, Vol.60(1), pp.149-170
DOI: 10.1016/j.brainresrev.2008.12.015
PMID: 19167425
PMCID: PMC2903433
NLM abbreviation: Brain Res Rev
ISSN: 0165-0173
eISSN: 1872-6321
Publisher: Elsevier B.V
Language: English
Date published: 2009
Academic Unit: Iowa Neuroscience Institute; Nursing; Anesthesia; Neuroscience and Pharmacology
Record Identifier: 9984007158602771

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