Elsevier

Current Anaesthesia & Critical Care

Volume 19, Issues 5–6, October–December 2008, Pages 338-343
Current Anaesthesia & Critical Care

Focus on: Pain medicine applications
Capsaicin: A review of its pharmacology and clinical applications

https://doi.org/10.1016/j.cacc.2008.07.003Get rights and content

Summary

Capsaicin is a naturally occurring alkaloid derived from chillies that is responsible for its hot pungent taste. It is an odourless fat soluble compound that is rapidly absorbed through the skin. Capsaicin is thought to produce analgesia by depleting substance P in small fibre nociceptor neurons on which Transient Receptor Potential action channel (subfamily V), type 1 (TRPV1) is predominantly located. It binds to the vanilloid receptor TRPV1, which acts as a molecular integrator of chemical and physical painful stimuli.

Topically applied capsaicin is useful in alleviating pain associated with diabetic neuropathy and chronic musculoskeletal pain. It is used to increase the bladder capacity and reduce incontinence in patients with bladder hyperactivity. Capsaicin can reduce post-operative nausea and vomiting when applied at acupressure points. It may be used to treat pruritis associated with renal failure and protect the stomach against non-steroidal anti-inflammatory drug induced gastritis. The development of capsaicin analogues and TRPV1 antagonists may provide more effective and better tolerated therapeutic agents in the future. Synthetic agents that are less pungent and target the TRPV1 receptor may prove to be more efficacious and more tolerable than naturally occurring capsaicin for the treatment of pain and inflammatory disease states.

Section snippets

Chemistry

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is a naturally occurring alkaloid extracted from fruit of the capsicum plant family. It is a member of the vanilloid family of compounds such as vanillin from vanilla, eugenol from bay leaves and cloves, zingerone from ginger and capsaicin from hot peppers.4 The vanilloids possess a vanillyl (4-hydroxy-3-methoxybenzyl) moiety and this confers their biological activity. Structurally, like other vanilloids, capsaicin has a benzene ring and long

Dosage and administration

Capsaicin is currently available as a topical cream in either a 0.025% or a 0.075% preparation. The recommended dosing is application 2–4 times daily to the affected areas. Parenteral capsaicin preparations are not available currently.

Pharmacokinetics

Topical capsaicin is well absorbed from the skin. Maximal cutaneous concentrations of capsaicin are rapidly achieved when capsaicin is applied topically. These concentrations are greater with isopropyl preparations compared with propylene glycol or mineral oil preparations. The half-life of capsaicin is approximately 24 h.8 In a study of 12 subjects the topical application of 3% solutions of capsaicin (55% capsaicin, 35% hydrocapsaicin and 10% other analogues) using three different vehicle

Mechanism of action

The mechanism of action of capsaicin and other vanilloids has been extensively studied over the past decade.2 Nearly 20 years ago, it was demonstrated that capsaicin releases substance P from afferent nociceptive neurons.3 Capsaicin activates afferent nociceptive neurons and evokes sensations ranging from hotness to burning. Its analgesic properties are mediated by the depletion of substance P that leads to the desensitisation of small afferent sensory neurons.

Capsaicin and other vanilloids

Adverse effects

Topical application of capsaicin causes irritation and burning. Approximately 54% of patients using capsaicin experience one or more local adverse events (compared to 15% with placebo).1 This corresponds to a number needed to harm (NNH) of 2.5. If withdrawal from active treatment is used as a measure the number needed to harm is closer to 10. The initial burning side effect of capsaicin cannot be reliably prevented with the use of topical local anaesthetics and this is a major limitation in the

Clinical uses

Capsaicin has been used for a number of diverse clinical conditions. The efficacy of the clinically significant uses of capsaicin is summarised in Table 1.

Future directions and therapies

A greater understanding of the mechanism of action of agonists and antagonists at the TRPV1 receptor and the structural activity relationships between these will enable the development of more effective and tolerable therapeutic agents. Woolf suggested that adding capsaicin into extended release drugs such as oxycontin and ritalin would be a safe way to deter abuse. When taken as prescribed, the capsules release their active ingredients over time, but when crushed, chewed, injected or snorted,

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