Schwann Cell TRPA1, a Proalgesic Ion Channel, Mediates Neuroinflammation and Fibromyalgia-Associated Behaviours in Mice

Transient receptor potential ankyrin 1 (TRPA1) is an ion channel that integrates the somatosensory system and is specialised in detecting thermal, mechanical, and chemical stimuli. It acts as both a sensor and an amplifier of reactive oxygen and nitrogen species, carbonylic species and lipid peroxidation products, which are overproduced in several painful conditions, including fibromyalgia. Studies have linked TRPA1 to heightened sensitivity to mechanical and cold pain in fibromyalgia patients. In a preclinical mouse model of fibromyalgia induced by reserpine administration, activated Schwann cells expressing TRPA1 trigger an intracellular pathway that leads to the production of reactive oxygen species (ROS) via NADPH oxidase (NOX) 1 and to the recruitment of macrophages in the mouse sciatic and trigeminal nerves. Such mechanisms contribute to mechanical and cold hypersensitivity and early anxiety- and depression-like behaviours. Future translational studies will be essential to validate whether pharmacological modulation of the Schwann cell TRPA1/NOX1 pathway could provide clinical benefit in fibromyalgia. (Figure presented.).