Exploring Novel Therapeutic Targets in the Common Pathogenic Factors in Migraine and Neuropathic Pain

Abstract

Migraine and neuropathic pain (NP) are evocative of painful, disabling, chronic conditions which exhibit resembling symptoms and thus considered to share a common etiology. Calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant search for more effective therapeutic targets for pain management. This scoping review overviews human studies of common pathogenic factors in migraine and NP to explore potential novel therapeutic targets. CGRP causes inflammation in the meninges; monoclonal antibodies and inhibitors target CGRP. Gluta-mate-induced hyperexcitability and subsequent sensitization are closely linked to an alteration of the tryptophan (Trp)-kynurenine (KYN) metabolic system; the Trp-KYN system may serve as a potential target. Microglial overaction is observed in migraine and NP; modifying the microglial activity may be a possible approach. Cytokine-induced inflammation is a leading hypothesis of the pathogenesis of the conditions; alleviating neuroinflammation may complement a pain-relieving armamentarium. Transient receptor potential (TRP) ion channels evoke the release of several substances; TRP ion channels may potentially emerge as new targets. The endocannabinoid system plays a major role in the pain trafficking pathway; modification of the system may open a new path toward discovery of new analgesics. Here we highlight the mechanism of those common pathogenic factors to explore therapeutic targets for innovative pain management in migraine and NP.

Activated Tryptophan-Kynurenine metabolic system in the human brain is associated with learned fear

“…The kynurenine (KYN) metabolic pathway, as a crucial component of Trp catabolism, is primarily responsible for disrupting Trp metabolism. Consequently, all processes associated with the metabolism of Trp into the KYN pathway have been extensively investigated and documented in both humans and animals (Chess et al, 2009;Balogh et al, 2021;Tanaka et al, 2021b;Polyák et al, 2023;Tajti et al, 2023). Indeed, it has been widely described that stress-induced situations can activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to increased levels of corticosterone (CORT) and inflammatory processes.…”