Topical capsaicin. The fire of a ‘hot’ medicine is reignited

Figures & data

Figure 1. The chemical structure of capsaicin.

Box 1. Drug summary.

Drug name (generic)	Capsaicin
Indications	Neuropathic pain Joint disease (arthritis) Neuropathic itch Dermatological and localized itch Systemic itch (uremic pruritus)
Route of administration	Topical cream or patch Intranasal Intravesical Oral (dietary-culinary)
Pharmacology description/mechanism of action	TRPV1 receptor agonist initially produces nerve excitation, substance-P release and then prolonged depletion of substance P and desensitization, ultimately blocking nerve transmission in capsaicin-sensitive unmyelinated polymodal C nociceptors. Decreases density of TRPV1-positive epidermal nerve endings
Chemical structure/name	Trans-8-methyl-N-vanillyl-non- 6-enamide
Molecular formula	C18H27NO3
Molar mass	305.41 g/mol
Physico-chemical properties	Melting point: 62 – 65°C Boiling point: 210 – 220°C @ 0.01 Torr Water-insoluble, lipophilic, soluble in ethanol
Analogs and related compounds	Dihydrocapsaicin, nordihydrocapsaicin, homodihydrocapsaicin, homocapsaicin (from Capsicum extract) RTX (resiniferatoxin, a more potent TRPV1 agonist than capsaicin) Capsazepine (TRPV1 antagonist) Rutaecarpine

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Table 1. TRPV1-independent pharmacological actions of capsaicin.

Mechanism of action	Studies
Blockade of K1 ion channels	Dubois 1982 [128]; Petersen et al. 1987 [129]; Kehl 1994 [130]; Kuenzi and Dale 1996 [131]
Inhibition of NADH- oxidoreductase and other enzymes	Shimomura et al. 1989 [132]
Alters membrane fluidity/elasticity	Meddings et al. 1991 [133]; Aranda et al. 1995 [134]
Inhibitory effect of capsaicin on thrombocyte aggregation (anticoagulant effect)	Hogaboam and Wallace 1991 [135]
Inhibition of activity of clotting factors VIIIc and IX	Murray et al. 2009 [115]
Competitive inhibitor of tyrosyl-tRNA synthetase	Cochereau et al. 1996 [136,137]
Causes degeneration in neurons not expressing TRPV1	Ritter and Dinh 1993 [138]

Table 2. Clinical indications of topical capsaicin for pain relief.

Disease type	Condition	Study
Neuropathies	Meralgia paraesthetica Burning mouth syndrome Postherpetic neuralgia Diabetic neuropathy Oral neuropathic pain Trigeminal neuralgia Reflex sympathetic dystrophy HIV-related neuropathy	[84]
Joint disease	Osteoarthritis rheumatoid arthritis (mixed results)
Other painful conditions	Guillain-Barre syndrome	Morgenlander et al. 1990 [139]
	Fibromyalgia	Kroenke et al. 2009 [140]
	Postmastectomy pain syndrome	Watson et al. [80,81]
	Stump pain	Rayner et al. 1989 [141] Weintraub et al. 1990 [142]

Table 3. Indications of topical capsaicin to relieve itch and improve dermatological disorders.

Source of itch	Condition
Neuropathic itch	Notalgia paraesthetica Brachioradial pruritus Post-herpetic neuralgia (PHN)
Dermatological conditions	Itch of psoriasis Lichen simplex chronicus Prurigo nodularis Lipodermatosclerosis, lobular panniculitis* Alopecia areata
Systemic itch	Uremic pruritus (patients on hemodialysis)
Localized itch	Vulvar vestibulitis Perianal pruritus
Miscellaneous forms of itch	Aquagenic pruritus Pruritus sine materia (idiopathic, itch with no apparent cause)

*Case reports.

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