Capsaicin provides analgesia by which mechanism, and what is a common initial sensation?

• A. Degradation of substance P with desensitization of nociceptors; burning or stinging sensation initially
• B. Blockade of central mu receptors with immediate numbness
• C. Inhibition of COX enzymes with rapid relief
• D. Activation of endorphin receptors causing euphoria

Answer: (A)

Capsaicin relieves pain by exhausting a key pain-carrying chemical in peripheral nerves. It binds to TRPV1 receptors on C-fiber nociceptors and triggers an initial surge of activity that releases substance P, producing the characteristic burning or stinging sensation. With continued exposure, substance P is depleted and the nociceptive terminals become desensitized, so the nerves transmit less pain signals. That combination—release and subsequent depletion of substance P with desensitization of nociceptors—explains the analgesia produced by capsaicin. Other options describe opioid receptor blockade, COX inhibition, or endorphin receptor effects, which are not how capsaicin works.