Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Biology, Life Sciences & Biomedicine - Other Topics, SENSORY NEURONS, INFLAMMATION INCREASES, VANILLOID RECEPTOR-1, IN-VITRO, HYPERALGESIA, ANTAGONIST, ACTIVATION, MOUSE, MODEL, TRP channels, inflammatory pain, mouse, neuroscience, sensory neurons, Animals, Female, Ganglia, Spinal, Hindlimb, Hot Temperature, Inflammation, Male, Mice, Mice, Inbred C57BL, Nociceptors, TRPA1 Cation Channel, TRPM Cation Channels, TRPV Cation Channels, Up-Regulation, C14/17/091#54271207, G0B7620N#55525059, 0601 Biochemistry and Cell Biology, 31 Biological sciences, 32 Biomedical and clinical sciences, 42 Health sciences

Abstract:

Genetic ablation or pharmacological inhibition of the heat-activated cation channel TRPM3 alleviates inflammatory heat hyperalgesia, but the underlying mechanisms are unknown. We induced unilateral inflammation of the hind paw in mice, and directly compared expression and function of TRPM3 and two other heat-activated TRP channels (TRPV1 and TRPA1) in sensory neurons innervating the ipsilateral and contralateral paw. We detected increased Trpm3 mRNA levels in dorsal root ganglion neurons innervating the inflamed paw, and augmented TRP channel-mediated calcium responses, both in the cell bodies and the intact peripheral endings of nociceptors. In particular, inflammation provoked a pronounced increase in nociceptors with functional co-expression of TRPM3, TRPV1 and TRPA1. Finally, pharmacological inhibition of TRPM3 dampened TRPV1- and TRPA1-mediated responses in nociceptors innervating the inflamed paw, but not in those innervating healthy tissue. These insights into the mechanisms underlying inflammatory heat hypersensitivity provide a rationale for developing TRPM3 antagonists to treat pathological pain.