TRPV1 is primarily expressed on, small myelinated and unmyelinated medium size, sensory neurons in dorsal root and trigeminal ganglia, where sensory neurons cluster. TRPV1 receptors are also found in muscles, joints, the urinary bladder and kidneys. The functional activity of TRPV1 has been demonstrated, within the central nervous system, in the spinal cord and specific sites in the brain including the hypothalamus, cerebellum, locus coeruleus, periaqueductal grey and cortex. Activation of TRPV1 sets off an influx of calcium and sodium ions which in turn initiates a cascade of events that result in membrane depolarization, neuronal firing and transduction of neural impulses. TRPV1 phosphorylates as a response to several algesic agents, resulting in a lower threshold of channel activation. Some substances such as bradykinin, nerve growth factor and protons have been reported to sensitize the TRPV1 receptor. Activation of TRPV1 results in the release of pro-nociceptive peptides, which decreases when treated with TRPV1 antagonists. In general, most channel antagonists bind in the pore region, interacting with residues from all four monomers of the tetrameric channel.