Abstract
Transient receptor potential vanilloid 1 (TRPV1), a non-selective cation channel, is a receptor activated by high temperatures and chemical agonists such as the vanilloids and protons. Because of these properties, TRPV1 has emerged as a polymodal nocisensor of nociceptive afferent neurons. TRPV1 is thought to be a central transducer of hyperalgesia and a prime target for controlling pain pharmacologically because it is a point where many proalgesic pathways converge and it is upregulated and sensitized by inflammation and injury. However, whether TRPV1 agonists promote or inhibit inflammation remains unclear. We recently demonstrated that SA13353 (1-[2-(1-adamantyl)ethyl]-1-pentyl-3-[3-(4-pyridyl)propyl]urea), a novel TRPV1 agonist, inhibits tumor necrosis factor-a production by the activation of capsaicin-sensitive afferent neurons and reduces the severity of symptoms in kidney injury, lung inflammation, arthritis, and encephalomyelitis. These results suggest that TRPV1 agonists may act as anti-inflammatories in certain inflammatory and autoimmune conditions in vivo. Given the potential deleterious effects of inhibiting the population of channels with a protective function, caution should be taken in the use of potent TRPV1 antagonists as a general strategy to treat inflammation. Further studies are required to clarify the role of TRPV1 and neuropeptides, which are released because of TRPV1 activation in inflammation and autoimmune diseases.
Highlights
Voltage-dependent Ca2+ channels are well known for causing Ca2+ influx into the cell
Transient receptor potential vanilloid 1 (TRPV1) is predominantly expressed in neurons with small and medium diameters that are important in the development of neurogenic pain and inflammation [2] and to a lesser extent in non-peptidergic neurons (Aδ-fibers) that play a critical role in mediating chronic [3] and mechanical pain [4]
TRPV1 activation leads to the release of neuropeptides, such as substance P (SP), calcitonin gene-related peptides (CGRP), and somatostatin [8]
Summary
Voltage-dependent Ca2+ channels are well known for causing Ca2+ influx into the cell. Studies have focused largely on the role of neuropeptides, which are released in periphery from small diameter sensory C-fiber neuron by activation of TRPV1 in neurogenic inflammation [9,10]. Analysis of the molecular and functional properties of TRPV1 has shown that this ion channel is a polymodal nocisensor, which is subject to allosteric modulation by many proalgesic pathways. This property and its ability to become sensitized by proinflammatory mediators have raised enormous interest in TRPV1 as a prime transducer of pathological pain. The role of TRPV1 in inflammation and autoimmune diseases is controversial; several studies have demonstrated a proinflammatory effect [18,19], while others have identified a protective role of TRPV1 in systemic inflammation and sepsis [20,21,22]
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