The role of TRPV1 receptors in pain evoked by noxious thermal and chemical stimuli

Abstract

Transient receptor potential receptors (TRP) on primary afferent neurons respond to noxious and/or thermal stimuli. TRPV1 receptors can be activated by noxious heat, acid, capsaicin and resiniferatoxin, leading to burning pain or itch mediated by discharges in C polymodal and Adelta mechano-heat nociceptors and in central neurons, including spinothalamic tract (STT) cells. Central nociceptive transmission involves both non-NMDA and NMDA receptors, and inhibitory interneurons as well as projection neurons contribute to the neural interactions. Behavioral consequences of intradermal injection of capsaicin include pain, as well as primary and secondary hyperalgesia and allodynia. Primary hyperalgesia depends on sensitization of peripheral nociceptors, whereas, secondary hyperalgesia and allodynia result from sensitization of central nociceptive neurons, such as STT cells. Central sensitization is associated with enhanced responses to excitatory amino acids and decreased responses to inhibitory amino acids. The mechanism of the increase in responses to excitatory amino acids includes phosphorylation of NR1 subunits of NMDA receptors and GluR1 subunits of AMPA receptors. Central sensitization depends on activation of several protein kinases and other enzymes, such as nitric oxide synthase. This process is regulated by protein phosphatases. Central sensitization can be regarded as a spinal cord form of long-term potentiation.