1.Research Background
TRPV1, the transient receptor potential vanilloid 1, has been risen the concerns for the reason that it is link to the target of the pain. the transient receptor potential vanilloid 1 is a novel member of the transient receptor potential (TRP) family of ion channels.
1) TRP family
TRP channels are largely expressed on the plasma membrane in numerous types of the cells, also including the neurons cells. There are seven families of TRP. They are TRPC, TRPV, TRPM, TRPA, TRPP, TRPML and TRPN, among which the letters C, V, M, A, P, M, L, N stand for canonical, vanilloid, melastatin, ankyrin, polycystin, mucolipin and Drosophila NOMPC respectively. Recently the eighth TRP family was indentified and named as TRPY in which the Y represents yeast.TRP superfamily is based on the differences in their amino acid sequences and topological structures, while it is difficult to differentiate the function of individual family and member simply according to the classification. Actually, TRPs play a plenty of physiological and pathological roles in response to various extracellular and intracellular stimuli, such as changes of temperature pH, or osmolarity, injury, depletion of calcium stores, as well as volatile chemicals and cytokines. Once activated, TRP channels function as an integrator of several signaling pathways to elicit a serial of responses. TRPs share common structure features, including six putative transmembrane spanning domains with intracellular C and N termini and a pore lining between the fifth and sixth transmembrane domains.
2) TRPV1
As for TRPV, it is classified as Group 1 TRP channel because of the strongest similarity with Drosophila TRP. There are six different members in this family. Compared to the rest of the members, TRPV1 was first identified and cloned in the late 1990s. it can be activated by multiple stimuli, such as moderate heat (ge;43℃), low pH, capsaicin, ethanol endogenous lipids, black pepper, and garlic as well as inflammatory mediators. The transient receptor potential vanilloid 1 is expressed in most neurons and widely investigated. In nerve injury associated with neuropathic pain and chronic pain, TRPV1 plays a central role. The transient receptor potential vanilloid 1 is regarded as a major target for the development of novel agents for the control of pain and visceral hyperrexia in inflammatory conditions.
For one thing, the transient receptor potential vanilloid 1 is predominantly expressed by primary afferent neurons subserving nociception-that is, sensory neurons with mostly unmyelinated fibers. For another, TRPV1 in nociceptive afferent neurons is upregulated in inflammation, which is true both for rodents with experimental colitis induced by trinitrobenzene sulfonic.
3 ) The advantage of TRPV1 antagonist
The transient receptor potential vanilloid 1 activation with agonists is known to have analgesic effects because it leads to desensitization of sensory neurons, making them less sensitive to painful stimuli. However, prolonged use of agonists such as topical muscle pain relievers containing capsaicin as the active component, is associated with side effects such as burning sensation, irritation , and neurotoxicity due to continuous influx of Ca2 ions into the cells. TRPV1 receptor antagonists on the other hand inhibit the activation of the primary sensory neurons and therefore may have fewer side effects than TRPV1 agonist.
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