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Etiology and Pharmacology of Neuropathic Pain

Alles, SRA; Smith, PA; (2018) Etiology and Pharmacology of Neuropathic Pain. Pharmacol Reviews , 70 (2) pp. 315-347. 10.1124/pr.117.014399. Green open access

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Injury to or disease of the nervous system can invoke chronic and sometimes intractable neuropathic pain. Many parallel, interdependent, and time-dependent processes, including neuroimmune interactions at the peripheral, supraspinal, and spinal levels, contribute to the etiology of this "disease of pain." Recent work emphasizes the roles of colony-stimulating factor 1, ATP, and brain-derived neurotrophic factor. Excitatory processes are enhanced, and inhibitory processes are attenuated in the spinal dorsal horn and throughout the somatosensory system. This leads to central sensitization and aberrant processing such that tactile and innocuous thermal information is perceived as pain (allodynia). Processes involved in the onset of neuropathic pain differ from those involved in its long-term maintenance. Opioids display limited effectiveness, and less than 35% of patients derive meaningful benefit from other therapeutic approaches. We thus review promising therapeutic targets that have emerged over the last 20 years, including Na+, K+, Ca2+, hyperpolarization-activated cyclic nucleotide-gated channels, transient receptor potential channel type V1 channels, and adenosine A3 receptors. Despite this progress, the gabapentinoids retain their status as first-line treatments, yet their mechanism of action is poorly understood. We outline recent progress in understanding the etiology of neuropathic pain and show how this has provided insights into the cellular actions of pregabalin and gabapentin. Interactions of gabapentinoids with theα2δ-1 subunit of voltage-gated Ca2+channels produce multiple and neuron type-specific actions in spinal cord and higher centers. We suggest that drugs that affect multiple processes, rather than a single specific target, show the greatest promise for future therapeutic development.

Type: Article
Title: Etiology and Pharmacology of Neuropathic Pain
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1124/pr.117.014399
Publisher version: http://dx.doi.org/10.1124/pr.117.014399
Language: English
Additional information: Copyright © 2018 by The Author(s) This is an open access article distributed under the CC BY Attribution 4.0 International license.
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10045021
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