The Dopaminergic Encoding of Pain and Pain Relief in the Mesolimbic Pathway

Abstract

Elucidating the chemical changes that underlie dysfunction of the central nervous system requires tools and techniques that enable rapid and accurate neurotransmitter quantification. The dopaminergic system is of major interest in many research groups due to its involvement in Parkinson’s disease, chronic pain, schizophrenia, and many more conditions. However, dopamine measurement in the CNS is challenging due to complex signaling dynamics. Phasic signals occur on the second to sub-second temporal regime while tonic changes arise over minutes to hours or longer. Presently, tonic and phasic dopaminergic signals cannot be measured simultaneously at a single probe. Using fast-scan cyclic voltammetry (FSCV) and fast-scan controlled-adsorption voltammetry (FSCAV) these studies investigated the response of the mesolimbic dopamine system to pain and pain relief as well as drug therapies. Opioids, which are known to interact with the mesolimbic reward pathway, were given to determine their influence on tonic and phasic dopamine signaling dynamics in various pain states. Using rodent models for pain, these investigations elucidated: (1) how ongoing (or sustained) pain alters both tonic and phasic dopamine release, (2) that acute thermal pain and pain relief cause a biphasic dopaminergic response in the mesolimbic pathway, and (3) a modulatory effect of mu opioids in the anterior cingulate cortex on mesolimbic dopamine release during acute pain. Thus, enhanced understanding of the the underlying biochemical mechanisms involved in pain perception and response will facilitate the development of more effective, less addictive pain therapeutics.