Question: 

Acetylsalicylic acid (ASA) has long been used for the treatment of pain but its efficacy in the early phase of inflammation besides the long known one in the late phase remains elusive. It was suggested that ASA directly inhibit the native capsaicin receptor TRPV1 (Neuroscience Letters 320, 2002:61ff). We therefore investigated the effect of ASA-like drugs on TRPV1 using the calcium imaging technique.

Methodology: 

Full-length rat TRPV1-GFP was transiently transfected in HEK293 cells, loaded with FURA-2-AM and investigated using calcium-imaging. Cells were activated repetitively with capsaicin (300nM for 30s), 30s before and during the second stimulus capsazepine (CPZ), ASA, methyl salicylate (MS), salicylic acid (SA), vehicle or combinations of those were applied.

Results: 

Capsaicin activated TRPV1 cells with an EC50 of about 200nM that was inhibited by the competitive antagonist CPZ (IC50 about 30nM). ASA, SS, and MS (1mM, each) significantly reduced capsaicin responses by about 59%, 61% and 19%, respectively (p<0.001, each, unpaired T-Test vs. vehicle). However, increasing doses of ASA, SA and MS as well as co-application of ASA with CPZ reduced the amount of inhibition. ASA, MS or SA alone (up to 100mM) did not increase intracellular calcium.

Conclusion: 

These results suggest a new mechanism for the action of ASA-like drugs directly at the nociceptive TRPV1. Because SS and MS lack an acetylic side chain, we can exclude any mechanism of acetylation as for the well-known COX inhibition. We suggest a direct, immediate and complex interaction of those drugs with the capsaicin receptor that needs further clarification.