The transient receptor potential vanilloid 1 and ankyrin 1 (TRPV1 and TRPA1, respectively) channels are members of the TRP superfamily of structurally related, non‐selective cation channels. It is rapidly becoming clear that the functions of TRPV1 and TRPA1 interlink with each other to a considerable extent. This is especially clear in relation to pain and neurogenic inflammation where TRPV1 is coexpressed on the vast majority of TRPA1‐expressing sensory nerves and both integrate a variety of noxious stimuli. The more recent discovery that both TRPV1 and TRPA1 are expressed on a multitude of non‐neuronal sites has led to a plethora of research into possible functions of these receptors. Non‐neuronal cells on which TRPV1 and TRPA1 are expressed vary from vascular smooth muscle to keratinocytes and endothelium. This review will discuss the expression, functionality and roles of these non‐neuronal TRP channels away from sensory nerves to demonstrate the diverse nature of TRPV1 and TRPA1 in addition to a direct role in pain and neurogenic inflammation.

Objective To investigate the involvement of transient receptor potential ankyrin 1 (TRPA1) in inflammatory hyperalgesia mediated by tumor necrosis factor α (TNFα) and joint inflammation. Methods Mechanical hyperalgesia was assessed in CD1 mice, mice lacking functional TRP vanilloid 1 (TRPV1^−/−) or TRPA1 (TRPA1^−/−), or respective wild‐type (WT) mice. An automated von Frey system was used, following unilateral intraplantar injection of TNFα or intraarticular injection of Freund's complete adjuvant (CFA). Knee swelling and histologic changes were determined in mice treated with intraarticular injections of CFA. Results TNFα induced cyclooxygenase‐independent bilateral mechanical hyperalgesia in CD1 mice. The selective TRPV1 receptor antagonist SB‐366791 had no effect on mechanical hyperalgesia when it was coinjected with TNFα, but intrathecally administered SB‐366791 attenuated bilateral hyperalgesia, indicating the central but not peripheral involvement of TRPV1 receptors. A decrease in pain sensitivity was also observed in TRPV1^−/− mice. Intraplantar coadministration of the TRPA1 receptor antagonist AP‐18 with TNFα inhibited bilateral hyperalgesia. Intrathecal treatment with AP‐18 also reduced TNFα‐induced hyperalgesia. CFA‐induced mechanical hyperalgesia in CD1 mice was attenuated by AP‐18 (administered by intraarticular injection 22 hours after the administration of CFA). Furthermore, intraarticular CFA–induced ipsilateral mechanical hyperalgesia was maintained for 3 weeks in TRPA1 WT mice. In contrast, TRPA1^−/− mice exhibited mechanical hyperalgesia for only 24 hours after receiving CFA. Conclusion Evidence suggests that endogenous activation of peripheral TRPA1 receptors plays a critical role in the development of TNFα‐induced mechanical hyperalgesia and in sustaining the mechanical hyperalgesia observed after intraaarticular injection of CFA. These results suggest that blockade of TRPA1 receptors may be beneficial in reducing the chronic pain associated with arthritis.