Hot peppers make it hurt less – Binshtok and colleagues reported one of those very clever experiments that creates envy from those less imaginative. They used capsaicin to selectively open TRPV1 channels allowing an otherwise impermeant local anesthetic (QX-314) to enter and block the sensory channel with absolutely no motor blockade. QX-314 is a charged lidocaine derivative that will not penetrate neuronal membranes and thus has no local anesthetic activity when applied to small sensory nerves. Capsaicin is a selective agonist for the noxious heat sensitive channel TRPV1 but not for motor channels. The effect of capsaicin on the channel allowed QX-314 access to the local anesthetic site of action and thus blocked further sodium influx though these channels. Hind paw injection of QX-314 together with capsaicin produced a long acting (> 2h) increase in mechanical and thermal nociceptive thresholds. When applied near the sciatic nerve there was a long acting decrease in pain sensitivity without motor blockade in contrast to application of lidocaine which produced both sensory and motor block (Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers. Nature 2007;449:607-610).
David S. Smith, M.D., Ph.D.
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