Functional interactions between glutamate receptors and TRPV1 in trigeminal sensory neurons

Background Elevated glutamate levels within injured muscle exacerbate pain conditions and modulate functional properties of muscle nociceptors via peripheral glutamate receptors. Direct injections of capsaicin in muscle tissue significantly lower mechanical thresholds, and the blockade of TRPV1 attenuates mechanical hyperalgesia resulting from eccentric muscle contraction. This study explores how the two receptorchannel systems that have been independently implicated in muscle pain and hyperalgesia interact together, which should offer novel perspectives on how various receptors and channels in nociceptors operate as ‘functional units’. We hypothesized that activation of peripheral glutamate receptors leads to TRPV1-dependent mechanical hyperalgesia via distinct intracellular signaling pathways.