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Developments in Understanding Diffuse Noxious Inhibitory Controls: Pharmacological Evidence from Pre-Clinical Research

Research output: Contribution to journalReview articlepeer-review

Original languageEnglish
Pages (from-to)1083-1095
Number of pages13
JournalJournal of Pain Research
Volume14
DOIs
Published2021

Bibliographical note

Funding Information: KB and MWK are funded by a grant from the Academy of Medical Sciences (SBF004\1064) awarded to KB. DV receives funding from the European Union’ s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 814244. Funding Information: KB and MWK are funded by a grant from the Academy of Medical Sciences (SBF004\1064) awarded to KB. DV receives funding from the European Union?s Horizon 2020 research and innovation programme under the Marie Sk?odowska-Curie grant agreement No 814244. Publisher Copyright: © 2021 Kucharczyk et al. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Bulbospinal pathways regulate nociceptive processing, and inhibitory modulation of nociception can be achieved via the activity of diffuse noxious inhibitory controls (DNIC), a unique descending pathway activated upon application of a conditioning stimulus (CS). Numerous studies have investigated the effects of varied pharmacological systems on the expression status of a) DNIC (as measured in anaesthetised animals) and b) the descending control of nociception (DCN), a surrogate measure of DNIC-like effects in conscious animals. However, the complexity of the underlying circuitry that governs initiation of a top-down inhibitory response in reaction to a CS, coupled with the methodological limitations associated with using pharmacological tools for its study, has often obscured the exact role(s) of a given drug. In this literature review, we discuss the pharmacological manipulation interrogation strategies that have hitherto been used to examine the functionality of DNIC and DCN. Discreet administration of a substance in the spinal cord or brain is considered in the context of action on one of four hypothetical systems that underlie the functionality of DNIC/DCN, where interpreting the outcome is often complicated by overlapping qualities. Systemic pharmacological modulation of DNIC/DCN is also discussed despite the fact that the precise location of drug action(s) cannot be pinpointed. Chiefly, modulation of the noradrenergic, serotonergic and opioidergic transmission systems impacts DNIC/DCN in a manner that relates to drug class, route of administration and health/disease state implicated. The advent of increasingly sophisticated interrogation tools will expedite our full understanding of the circuitries that modulate naturally occurring pain-inhibiting pathways.

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