Journal of Pain Research (Apr 2021)
Developments in Understanding Diffuse Noxious Inhibitory Controls: Pharmacological Evidence from Pre-Clinical Research
Abstract
Mateusz Wojciech Kucharczyk,* Diego Valiente,* Kirsty Bannister Central Modulation of Pain Group, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, SE1 1UL., UK*These authors contributed equally to this workCorrespondence: Kirsty BannisterWolfson Centre for Age-Related Diseases, Guy’s Campus, King’s College London, London, SE1 1UL, UKTel +44 2078484617Fax +44 2078486806Email [email protected]: 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.Keywords: endogenous pain modulation, descending pain control, diffuse noxious inhibitory controls, descending control of nociception, conditioned pain modulation, monoamines
