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ORIGINAL ARTICLE
Year : 2009  |  Volume : 21  |  Issue : 2  |  Page : 51-54 Table of Contents   

Capsaicin-fighting fire with fire


Department of Oral Medicine, Diagnosis and Radiology, KLE'S V.K. Institute of Dental Sciences, Belgaum, Karnataka, India

Date of Web Publication1-Dec-2009

Correspondence Address:
Arvind Shetti
1386/2a Plot no 14 Shiva Basav Sadan Jadhav Nagar, Belgaum, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-1363.57885

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   Abstract 

Chronic pain conditions involving the maxillofacial region represent a major health problem and patients with persistent pain are difficult to manage successfully. Most of these conditions are often comorbid with additional health issues. Capsaicin has been studied in various models of pain and neuropathy. Currently, its best known use is as a topical analgesic and anti-inflammatory. Its use as a noxious stimulus offers several benefits and has been used with considerable success in conditions like postherpetic neuralgia, atypical facial pain, musculoskeletal pain etc. Adverse events from capsaicin are mainly at the application site (burning, stinging, erythema), and systemic events are rare. This review highlights the emerging evidence on the use of capsaicin in the commonly encountered orofacial pain conditions.

Keywords: Capsaicin, chronic orofacial pain, resiniferatoxin, vanilloid receptor


How to cite this article:
Agarwal P, Keluskar V, Bagewadi AS, Shetti A. Capsaicin-fighting fire with fire. J Indian Acad Oral Med Radiol 2009;21:51-4

How to cite this URL:
Agarwal P, Keluskar V, Bagewadi AS, Shetti A. Capsaicin-fighting fire with fire. J Indian Acad Oral Med Radiol [serial online] 2009 [cited 2019 Dec 12];21:51-4. Available from: http://www.jiaomr.in/text.asp?2009/21/2/51/57885


   Introduction Top


Capsaicin is a chemical irritant that is the active ingredient in hot chili peppers of the genus Capsicum[Figure 1]. [1] A popular theory holds that the name Capsicum was derived from the Greek kapto, meaning "to bite", which appropriately describes the main characteristic of the fruit. The active ingredient in hot pepper was first isolated by Thresh (1846) more than a century ago. Capsaicin has been studied extensively to exploit its potential therapeutic value and as a means to probe the physiology of pain transmission. [2] Capsaicin has been in use for decades as a pharmacological tool to identify sensitive neurons and to explore the function of this class of neurons in the healthy organism or their contribution to disease states. The three characteristic effects of capsaicin (excitation/desensitization/neurotoxicity) can be used therapeutically but sensitization to capsaicin is of particular interest as a novel approach to mitigate neuropathic pain insensitive to traditional painkillers such as opiates. [1]


   Receptors Top


Capsaicin's effects are mediated via specific membrane receptors located on the terminals of primary afferent neurons. Resiniferatoxin is an analog of capsaicin isolated from the milky juice (latex) of Euphorbium resinifera and is about 1,000 times more potent. Chemically, capsaicin and resiniferatoxin are vanilloids; hence their receptor is termed the vanilloid receptor. Capsazepine is a competitive vanilloid receptor antagonist that inhibits capsaicin binding and reverses the physiologic effects of capsaicin, including its antinociceptive properties. Capsazepine is not an analgesic by itself, suggesting that there is no endogenous capsaicin-like ligand which is tonically activating the receptor in pain states. [1]


   Mechanism of Action/Pharmacology Top


The effect of capsaicin on pain is thought to be mediated through its effects on sensory neurons with unmyelinated C-fibers, which participate in the transmission of nociceptive information to the central nervous system and release a number of proinflammatory mediators involved in pain pathways. Capsaicin activates sensory nerve fibers through an ion channel known as vanilloid receptor Subtype 1 (Caterina et al., 1997). After activation of the vanilloid receptor Subtype 1, capsaicin and other vanilloids desensitize sensory neurons, making them refractory to subsequent noxious stimuli (Szallasi, 1996). However, the initial irritation due to excitation of sensory neurons by capsaicin causes uncomfortable side-effects. In addition to desensitizing C-fiber afferent neurons, capsaicin also alters the release from peripheral terminals of substance P, neurokinin A, calcitonin gene-related peptides, and other neurotransmitters/neuropeptides involved in inflammatory responses. The desensitization of C-fibers produced by capsaicin is caused by the depletion of these neuropeptides [Figure 2]. [3]


   Place in Therapy Top
[2]

Arthritis - Pain FDA Labeled Indication

It is indicated for the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, strains, and sprains. [4]

Guillain-Barre syndrome

Effective in treating pain associated with Guillain-Barre syndrome in one case report. [5]

Musculoskeletal pain FDA Labeled Indication

Indicated for the temporary relief of minor aches and pains of muscles joints associated with arthritis, simple backache, strains and sprains. [6]

Nasal polyp, Post-surgical, recurrence of; Prophylaxis

Intranasal application post surgery reduced recurrence of nasal polyps. [7]

Neuropathy - Postoperative complication

Topical capsaicin has reduced or eliminated post-surgery neuropathy caused by various types of surgery in a majority of subjects in a double-blind, placebo-controlled crossover trial. Ninety-nine cancer patients with post-surgery neuropathic pain were given capsaicin cream 0.075% or inert placebo to be applied to the painful area four times per day for eight weeks; in the next eight weeks, treatments were switched to the alternate compound. At the end of the first eight weeks, the capsaicin group experienced a 53% reduction in pain, compared to a 17% reduction in the placebo group. There was significantly more skin burning, redness, and coughing associated with capsaicin treatment. [8]

Post-herpetic neuralgia

Capsaicin appears to have some efficacy in this condition. In addition, it is considerably safer than most other regimens currently employed particularly antidepressants and neuroleptics. In an open trial of patients diagnosed with post-herpetic neuropathy, 56% of 23 patients treated with topical capsaicin (0.025%) had good to excellent pain relief at four weeks. [9],[10] Two other open trials of post-herpetic pain supported these findings [Table 1]. [11]

Pain, Refractory

It provides temporary relief to some types of refractory pain. Topical capsaicin 5-10%, applied after regional anesthesia, provided marked temporary relief in 9 of 10 patients with intractable pain and prolonged relief with repeated applications in 7 of 10 patients in an open trial. [12]

Psoriasis

Capsaicin reduces the itching, scaling and erythema of psoriasis in some patients. Concentration of 0.01% and 0.025% were both more effective than placebo in treating moderate to severe psoriasis in a double-blind study. [11]


   Capsaicin Analog Top


The ultrapotent capsaicin analog, RTX, is at present undergoing clinical trials. Compared to capsaicin, RTX has at least four major advantages:

  1. Because of its ultrapotency, it may be used in much lower concentrations (in theory, RTX is ultrapotent for the vanilloid receptor-mediated, desired actions of capsaicin only, but not for its receptor-unrelated side-effects, which makes capsaicin a 'double-edged sword);
  2. It favors desensitization (tachyphylaxis) to irritation, which is the main factor limiting the therapeutic use of capsaicin (the mechanisms underlying this phenomenon are discussed above); moreover, at least in rat experiments,
  3. It has a much broader therapeutic window: a full desensitization to pain or neurogenic inflammation may be achieved by means of a single RTX injection, without unacceptable toxicity; and, finally,
  4. Unlike capsaicin, it not only suppresses chemogenic pain but is effective against noxious heat-evoked pain in normal rats, or cold-evoked pain in animals with spinal cord injury. [2]



   Capsaicin Formulations Top


Capsaicin is available in various combinations with local anesthetics and analgesics in the concentration ranging from 0.025% to 0.075% in the form of gels, creams and sprays.

Generic and Brand Names of Capsaicin Products: Capsagel, Capsagesic-HP Arthritis Relief (high potency), Capsin, RT Capsin, Capsoderma, Capzasin, Capzasin-HP, Capzasin-P, Dolorac, Double Cap, Dr.s Cream, Eucalyptamint 2000, Menthac Arthritis Cream with Capsaicin, Pain Enz, Penecine Topical Pain Reliever, Rid-A-Pain, Salonpas Pain Patch with Capsaicin, Trixaicin, Trixaicin-HP, Zostrix, Zostrix-HP.


   Randomized Control Trials Top


Capsaicin was significantly better than placebo for the treatment of both neuropathic and musculoskeletal pain [Figure 3]. In neuropathic conditions, the mean treatment response rate (percentage of patients with at least 50% pain relief) at four weeks for capsaicin 0.075%, was 57% (range 53-75% in individual trials), and the mean placebo response rate was 42% (range 31-55%). The number needed to treat was 6.4 (95% confidence interval 3.8 to 21). The mean treatment response rate at eight weeks for capsaicin 0.075% was 60% (range 20-75%), and the mean placebo response rate was 42% (range 10-65%). The number needed to treat was 5.7 (4.0 to 10). These effects were supplementary to unchanged oral therapy.

In musculoskeletal conditions, the mean treatment response rate at four weeks for capsaicin 0.025% or plaster was 38% (range 34-42%) and the mean placebo response rate was 25% (range 17-37%). The number needed to treat was 8.1 (4.6 to 34). Only one of the three trials with efficacy data allowed concomitant oral therapy. [6]




   Adverse Reactions Top


Dermatologic

Local discomfort, characterized by burning, stinging, and redness of the skin occur frequently with capsaicin cream; local discomfort is increased when capsaicin cream is applied less than three to four times daily. These reactions usually diminish with continued therapy but can be persistent and severe in some patients. Burning and other local reactions were more common with 0.025% capsaicin cream as compared to a 0.01% cream in psoriasis patients in one study. Itching was also reported during initial applications in these patients. [14]

Neurologic

Topical capsaicin in concentrations of 1% or greater has been associated with neurotoxicity and thermal hyperalgesia. [15]

Respiratory

Capsaicin inhalation has been associated with cough and a transient increase in airway resistance. These effects are felt to be related to stimulation of sensory airway nerves. Inhaled cough induced by capsaicin has been exacerbated by pretreatment with angiotensin converting enzyme (ACE) inhibitors. [16]

Teratogenicity/Effects in Pregnancy

Fetal risk cannot be ruled out. Available evidence is inconclusive or is inadequate for determining fetal risk when used in pregnant women or women of childbearing potential.

Systemic administration

In high concentrations it can be toxic, causing degeneration of axons and axon terminals. In neonates, systemic administration results in gross neurotoxicity and death of cell bodies, leading to permanent sensory deficits. [15]


   Conclusion Top


Despite the disparities in the results of the past studies evaluating the efficacy of capsaicin, within the last decade, controlled trials have frequently suggested this compound as an effective topical analgesic in the control of various pain conditions. Although when topically applied, it has moderate to poor efficacy in the treatment of chronic musculoskeletal or neuropathic pain, it may be useful as an adjunct or sole therapy for a small number of patients who are unresponsive to, or intolerant of, other treatments. However, the wide distribution of its receptors also suggests that these drugs might cause a broad range of side-effects. The two major limitations that have to be overcome: first, low doses of the commercially available preparations (doses available are not more than 1%). Second, intense initial burning effects which reduces patient compliance. More, adequately powered, randomized controlled trials are necessary for a definitive assessment of this matter. Other therapeutic indications may eventually appear.

 
   References Top

1.Szallasi A, Blumberg PM. Vanilloid receptors: new insights enhance potential as a therapeutic target. Pain 1996;68:195-208.  Back to cited text no. 1      
2.Wachtel RE. Capsaicin. Regional Anesthesia and Pain Medicine 1999;24:361-3.  Back to cited text no. 2      
3.Chancellor MB, de Groat WC. Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder. J Urol 1999;162:3-11.  Back to cited text no. 3      
4.Deal CL, Schnitzer TJ, Lipstein E, Seibold JR, Stevens RM, Levy MD, et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther 1991;13:383-95.  Back to cited text no. 4      
5.Morgenlander JC, Hurwitz BJ, Massey EW. Capsaicin for the treatment of pain in Guillain-Barre syndrome. Ann Neurol 1990;28:199.   Back to cited text no. 5      
6.Mason L, Moore RA, Derry S, Edwards JE, McQuay HJ. Systematic review of topical capsaicin for the treatment of chronic pain BMJ 2004;328:991.   Back to cited text no. 6      
7.Zheng CQ, Wang ZM, Lacroix JS. Effect of intranasal treatment with capsaicin on the recurrence of polyps after polypectomy and ethmoidectomy. Acta Otolaryngol (Stockh) 2000;120:62-6.   Back to cited text no. 7      
8.Dubner R. Topical capsaicin therapy for neuropathic pain. Pain 1991;47:247-8.   Back to cited text no. 8      
9.Watson CP, Evans RJ, Watt VR. Post-herpetic neuralgia and topical capsaicin. Pain 1988;33:333-40.   Back to cited text no. 9      
10.Bernstein JE, Bickers DR, Dahl MV, Roshal JY. Treatment of chronic postherpetic neuralgia with topical capsaicin. J Am Acad Dermatol 1987;17:93-6.   Back to cited text no. 10      
11. Peikert A, Hentrich M, Ochs G. Topical 0.025% capsaicin in chronic post-herpetic neuralgia: efficacy, predictors of response and long-term course. J Neurol 1991;238:452-6.  Back to cited text no. 11      
12.Robbins WR, Staats PS, Levine J, Fields HL, Allen RW, Campbell JN, et al. Treatment of intractable pain with topical large-dose capsaicin: preliminary report. Anesth Analg 1998;86:579-83.   Back to cited text no. 12      
13.Bernstein JE, Parish LC, Rapaport M, Rosenbaum MM, Roenigk HH Jr. Effects of topically applied capsaicin on moderate and severe psoriasis vulgaris. J Am Acad Dermatol 1986;15:504-7.   Back to cited text no. 13      
14.Bernstein JE. Capsaicin in dermatologic disease. Semin Dermatol 1988;7:304-9.  Back to cited text no. 14      
15.Buck SH, Burks TF. The neuropharmacology of capsaicin: review of some recent observations [review]. Pharmacol Rev 1986;38:179-226.   Back to cited text no. 15      
16.Hakas JF. Topical capsaicin induces cough in patient receiving ACE inhibitor. Ann Allergy 1990;65:322.   Back to cited text no. 16      


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1]



 

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  In this article
    Abstract
    Introduction
    Receptors
    Mechanism of Act...
    Place in Therapy
    Capsaicin Analog
    Capsaicin Formul...
    Randomized Contr...
    Adverse Reactions
    Conclusion
    References
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