Investigation of the role of intracellular receptors NOD1 and NOD2 in the pathophysiology of chronic pain

Abstract

Among pattern recognition receptors (PRRs), the Toll-like receptors (TLRs) and NOD-like receptors (NLRs) are the most important and responsible for recognizing of pathogen-associated molecular patterns (PAMPs). Moreover, these PRRs also recognize damage-associated molecular patterns (DAMPs), endogenous substances released both in the damaged tissue as in circulation, and that mediate several physiopathological processes. Chronic pain is an important public health problem and, increasingly, there is a need to understand it in order to obtain new treatments. In the last years, advances have been achieved with regard to molecular mechanisms involved in the induction and maintenance of chronic pain. Accordingly, several studies have reported that glial cells present in the central nervous system, especially in the spinal cord, participate in these mechanisms, which are still not completely understood. It was recently shown that PRRs, such as the TLRs, participate in the process of glial activation and, in models of inflammation / infection of the central nervous system, the receptors NLRs and TLRs cooperate in the activation of glial cells, which leads us to hypothesize that also in chronic pain models, activation of microglia depends on NOD receptors. In the present study, we will evaluate the role of receptors NOD1 and NOD2 in the genesis of inflammatory and neuropathic chronic pain, focusing on its importance in the activation of glial cells and their signaling pathways (RIPK2). (AU)