Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is an active component of chilli peppers. It binds to TRPV1 (transient receptor potential channel) receptors which is a heat-activated calcium channel. It causes depletion of substance P and decrease the density of epidermal nerve fibres. The effect takes 3–4 weeks to manifest. It is available in 0.025 %, 0.075 % cream and 8 % patch. 0.075 % cream applied 3–4 times/day has shown efficacy in painful diabetic neuropathy and postherpetic neuralgia (NNT for 50 % pain relief is 6.7). It is associated with burning sensation which can be reduced by co-administration of glyceryl trinitrate or EMLA (eutectic mixture of local anaesthetics).

Eight percent patch (Qutenza): cutaneous patch containing 179 mg of capsaicin/280 cm² patch. It should be applied for 60 min and provides pain relief for up to 12 weeks. Adverse effects include redness, itching, blisters, papules and skin dryness.