TRPA1 as a therapeutic target for nociceptive pain.

Daniel Souza Monteiro de Araujo, Romina Nassini, Pierangelo Geppetti, Francesco De Logu

Expert opinion on therapeutic targets 2020 Oct

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Chronic pain affects approximatively 30-50% of the population globally. Pathologies such as migraine, diabetic neuropathy, nerve injury and treatment with chemotherapeutic agents, can induce chronic pain. Members of the transient receptor potential (TRP) channels, including the TRP ankyrin 1 (TRPA1), have a major role in pain. We focus on TRPA1 as a therapeutic target for pain relief. The structure, localization, and activation of the channel and its implication in different pathways to signal pain are described. This paper underlines the role of pharmacological interventions on TRPA1 to reduce pain in numerous pain conditions. We conducted a literature search in PubMed up to and including July 2020. Our understanding of the molecular mechanisms underlying the sensitization of central and peripheral nociceptive pathways is limited. Preclinical evidence indicates that, in murine models of pain diseases, numerous mechanisms converge on the pathway that encompasses oxidative stress and Schwann cell TRPA1 to sustain chronic pain. Programs to identify and develop treatments to attenuate TRPA1-mediated chronic pain have emerged from this knowledge. Antagonists explored as a novel class of analgesics have a new and promising target in the TRPA1 expressed by peripheral glial cells.

Citation

Daniel Souza Monteiro de Araujo, Romina Nassini, Pierangelo Geppetti, Francesco De Logu. TRPA1 as a therapeutic target for nociceptive pain. Expert opinion on therapeutic targets. 2020 Oct;24(10):997-1008