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Evidence that TRPA1 plays an important role in TNFα-induced mechanical hyperalgesia The mechanisms linking TNFα and inflammatory pain are unclear. Previously, we have shown that TRPV1 is involved in the thermal hyperalgesia induced by TNFα (Russell et al., 2009) and that TNFα levels are raised in a model of joint inflammation induced by CFA (Keeble et al., 2005). Here, we sought to investigate the contribution of TRPA1 receptors in inflammatory hyperalgesia induced by intraplantar (i.pl.) TNFα injection. Mechanical hyperalgesia was assessed in both hindpaws by using an automated Von Frey system. Measurements were taken before (baseline) and after treatment. Statistical analysis was carried out using ANOVA followed by Dunnet’s test for comparison of means. P values less than 0.05 were considered significant. Animals received TNFα (10 pmol/paw, ipsilateral paw) and Tyrode (50 µl/paw, contralateral paw). TRPA1 involvement was analyzed in WT and TRPA1 knockout (TRPA1KO) mice and also in CD1 mice treated with the selective TRPA1 receptor antagonist AP-18 (25 nmol/paw, co-injected with TNFα). TNFα evoked a significant and sustained bilateral mechanical hyperalgesia in WT mice (up to 7 days). On the other hand, TRPA1KO mice only exhibited ipsilateral hyperalgesia that was significant for up to 4 h after TNFα injection. In addition, local treatment with AP-18 significantly prevented TNFα-induced mechanical hyperalgesia in CD1 mice (2-4 h). Herein, these results show that TRPA1 is important to the development of TNFα-induced mechanical hyperalgesia. Thus, we present new and relevant evidence of TRPA1 participation in pain processing. We suggest TRPA1 plays a role in maintaining inflammatory hyperalgesia associated to TNFα.
Keeble, J., Russell, F., Curtis, B., Starr, A., Pinter, E., Brain, S.D. (2005) Arthritis Rheum. 52: 3248-3256. |
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