TRPV1 Agonism
Nociceptors are specialized nerve cell endings that are responsible for the sensation of pain. In people with neuropathic pain, primary afferent nociceptors that remain intact after disease or injury become persistently hyperactive, spontaneously transmitting excessive pain signals to the spinal cord in the absence of painful stimuli. It is postulated that these residual nociceptors become hyperactive as a result or exposure to higher-than-normal concentrations of neurotrophins such as nerve growth factor.
Nociceptors express a receptor called the transient receptor potential vanilloid 1 receptor (TRPV1—formerly known as vanilloid receptor 1 or VR1). TRPV1 is a ligand-gated ion channel activated by agonists such as capsaicin and other factors such as heat and acidosis. When capsaicin activates TRPV1, calcium enters the nerve fiber and pain signals are initiated. When TRPV1 is strongly activated through exposure to high concentrations of capsaicin, excessive calcium enters the nerve fibers, initiating processes that result in long-term yet reversible impairment of nociceptor function, temporarily reducing their ability to send pain signals.