Paradoxically, prolonged activation of TRPV1 with agonists, CAP and civamide, can reduce headache pain by causing a durable denervation of fibres that express this channel, but their clinical use has been restricted due to the severity of on-target side effects of burning pain and lacrimation, whilst clinical trials with TRPV1 antagonists are ongoing [23]. Here, TRPV1 is linked to Headache.