Capsaicin is the primary active component of the heat and pain-eliciting lipid-soluble fraction of the Capsicum pepper.{10293} Capsaicin is present in natural hot pepper extracts along with a number of impurities, including dihydrocapsaicin and several lesser impurities. Separation by HPLC is required in order to obtain capsaicin of consistently high purity and reproducible quality.{10294} VR1 is a heat-activated calcium ion channel which functions as part of the normal nociceptive pain pathway. Capsaicin elicits a sensation of burning pain by activation of VR1 on small, non-myelinated polymodal C-type nociceptive nerve fibers.{5122} Chronic application of capsaicin leads to desensitization of these pain fibers and has been widely exploited in various non-prescription pain remedies.