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REVIEW ARTICLE
Year : 2012  |  Volume : 2  |  Issue : 1  |  Page : 8-15

Capsaicin: A promising therapy - A critical reappraisal


Department of Pharmacology, J L N Medical College and Hospital, Ajmer, Rajasthan, India

Date of Submission06-Jul-2011
Date of Acceptance03-Aug-2011
Date of Web Publication23-Feb-2012

Correspondence Address:
Naveen Chhabra
c/o Dr. M. L. Aseri, I/3 J L N Medical College and Hospital Campus, Ajmer, Rajasthan
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2231-0738.93124

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   Abstract 

Capsaicin, major capsainoid, derived from dried fruit of chilli pepper, is synthesized in the interlocular septa of chilli peppers by addition of a branched-chain fatty acid to vanillylamine. An extensive, although largely forgotten, literature addresses the utility of the capsaicin therapy as either adjunctive or main treatment strategy for a number of diseases. Topical capsaicin has been shown to improve the outcome in neuropathic and musculoskeletal pain, post herpetic neuralgia, arthritic pain, burning mouth syndrome, pain due to fibromyalgia, psoriatic disorder, burning mouth syndrome, various allergic disorders, and as intranasally for cluster headache. Capsaicin is under development therapy for various diseases, it may develop as a new treatment therapy for a number of diseases in near future. However, studies with systemic ingestion are limited and have been shown gastrointestinal adverse effects, which may be major limitations to systemic capsaicin therapy.

Keywords: Capsaicin, pain, vanilloid receptor


How to cite this article:
Chhabra N, Aseri M L, Goyal V, Sankhla S. Capsaicin: A promising therapy - A critical reappraisal. Int J Nutr Pharmacol Neurol Dis 2012;2:8-15

How to cite this URL:
Chhabra N, Aseri M L, Goyal V, Sankhla S. Capsaicin: A promising therapy - A critical reappraisal. Int J Nutr Pharmacol Neurol Dis [serial online] 2012 [cited 2018 Nov 18];2:8-15. Available from: http://www.ijnpnd.com/text.asp?2012/2/1/8/93124


   Introduction Top


Capsaicin and several related compounds are called capsaicinoids. Capsaicinoids are derived from the dried fruit of the plants of the solanaceae family, produced as secondary metabolites by chilli peppers. Capsaicin is the main capsaicinoid in chilli peppers, followed by dihydrocapsaicin. Other minor capsaicinoids are nordihydrocapsaicin, homodihydrocapsaicin, homocapsaicin, and nonivamide. Besides these six natural capsaicinoids, one synthetic member of the capsaicinoid family also exists. P.A. Bucholz, first isolated the capsaicin molecule in 1816 in crystalline form, later again by L.T. Thresh. L.T. Thresh gave it name "capsaicin." Capsaicin was first synthesized by Spath and Darling. [1],[2] In 1961, similar substances were isolated from chilli peppers by the Kosuge and Inagaki, who named them capsaicinoids. [3],[4] Pure capsaicin is a hydrophobic, colorless, odorless, and crystalline to waxy compound. Capsaicin is synthesized in the interlocular septa of chilli peppers by addition of a branched-chain fatty acid to vanillylamine. Biosynthesis depends upon the AT3 gene, which is located at the pun 1 locus and which encodes a putative acetyltransferase. [5] IUPAC name for capsaicin is: 8-methyl-N-vanillyl 1-trans-6-nonenamide. Chemical Abstracts Service (CAS) registry number is 404-86-4. Capsaicin is a phenylpropanoid compound. [6]


   Chemical and Physical Properties of Capsaicin Top


Molecular formula

C 18 H 27 NO 3 ; molecular mass is: 305.41 g/mol; melting point; 62-65°C; boiling point 210-220°C @ 0.01 Torr; vapor pressure: Very low; specific gravity: 1.0073-1.1073.

Mechanism of action

Capsaicin, as a member of vanilloid family, binds selectively to vanilloid receptor subtype 1 (VR1). VR1 is ion-channel-type receptor that is related to transient receptor potential vanilloid 1 (TRPV1) receptor family and located on the membrane of pain and heat sensing neurons. [7],[8] By binding to VR1 receptor, the capsaicin molecule produces the same sensation that is produced by excessive heat or abrasive damage; this explains the burning pain caused by capsaicin. [9] Capsaicin also triggers release of the neuropeptide P from the C-type sensory nerve fibers. Neurons, not having TRPV1 receptors, remain unaffected. On prolonged activation of TRPV1 receptors having neurons by capsaicin depletes presynaptic substance P. Systemic exposure to low-dose capsaicin enhances sensory nerve functions and also increases substance P in nonneuronal tissues. [10] The capsaicin (vanilloid) receptor also plays an important role in transducing thermal and inflammatory pain. Mice lacking the VR 1 genes deficits in thermal- or inflammation-induced hyperalgesia, which confirms the involvement of this channel in pain sensation, especially the sensation of heat-evoked pain. [11]

Capsaicin differentially modulates voltage-activated calcium channel (VACC) currents in dorsal root ganglion (DRG) neurons of rats. Capsaicin decreases or increases VACC currents. This effect of capsaicin on different VACCs in small DRG neurones, which most likely express the TRPV1 receptor, may represent another mechanism of action of capsaicin in addition to opening of TRPV1. [12]

Capsazepine, a competitive antagonist at the vanilloid (capsaicin) receptor, blocks voltage-activated calcium currents in sensory neurones. The block of calcium current showed some voltage-dependence, but there was no indication of any selectivity of action for a calcium channel subtype. The data suggest that capsazepine, in addition to its competitive antagonism of vanilloid receptors, has a nonspecific blocking action on VACCs which should be taken into account when interpreting the effects of this substance on intact preparations in vitro or in vivo. [13]

Toxicity

Dermal toxicity


Capsaicin is highly irritant material. Dermal LD 50 is reported >512 mg/kg in mouse. Dermal exposure results in burning or stinging pain in humans. After prolonged exposure or in the presence of preexisting dermatitis, blistering and rashes occur. Dermal exposure in mouse ears causes edema within 1 hour of application. [14],[15] Capsaicin when applied to skin or mouth causes a long lasting desensitization. [16]

Eye toxicity

Intense tearing, pain, conjunctivitis, blepharospasm, and corneal lesions are reported in rats and mice. [14],[17]

Oral toxicity

Ingestion in large amount by adults or in small amounts by children causes nausea, abdominal pain, and diarrhea. The guinea pig appears to be the most susceptible species to the oral capsaicin toxicity. Acute oral LD 50 in guinea pig is 1.1 mg/kg, [18] while acute oral LD 50 reported in male mice is 118.8 mg/kg and 97.4 mg/kg in female mice. In male rats, it is 23.6 mg/kg and in female rats 29.7 mg/kg. [19] Oral lethal dose estimated in human is 0.5-5g/kg. [20] Respiratory paralysis is reported as cause of death after oral exposure.

Inhalation toxicity

Inhalation of capsaicin vapors causes lung irritation and sensitization, temporarily bronchoconstriction, cough, and incoordination of upper body movement in humans. [21] Airway resistance is increased in both mild asthamatics and nonasthamatics at the doses lower than that elicits the cough response. [22] A study comparing the effect of nebulized capsaicin (10−7 M, 0.03 g/m M, 0.03 g/m 3 ) to diluten alone on the pattern of breathing showed that capsaicin increases mean inspiratory flow. [23]

The effect of inhaled capsaicin has been studied in humans also. Inhaling 2.4 × 10−10 , and 2.4 × 10−9 M capsaicin results in a dose dependant fall in specific airways conductance (maximum fall was reported within 20 seconds of exposure which lasts for less than 60 seconds). There was no difference in the magnitude or duration of bronchoconstriction between normal, smoking, or asthamatic patients. [24]


   Uses and Effects of Capsaicin Top


Capsaicin and antinociception

Capsaicin activates poorly myelinated primary afferent neurons, causes membrane depolarization and the opening of cation selective, ion channel which are blocked by ruthenium red (A polyvalent dye). Antinociception produced by capsaicin does not involve neurotoxicity, sensory neuropeptide depletion, activity at peripheral receptors; rather, systemic capsaicin produces antinociceptin by activating capsaicin receptors on afferent nerve terminals in the spinal cord. However, local or topical application of capsaicin block C-fiber conduction and inactive neuropeptide release from peripheral nerve endings. [25] On the basis of the ability of capsaicin ability to activate TRPV1 expressed in nociceptive sensory neurons, various topical and injectable formulations are being developed as potential treatment of various pain syndrome. Capsaicin (0.025-0.075%) is used in topical ointments to relieve the peripheral neuropathies. Capsaicin is key ingredient of a promising drug underdevelopment for postsurgical and osteoarthritic pain. The analgesic effect induced by capsaicin is enhanced in inflammatory states. Capsaicin induces its analgesic effect following an initial excitatory response. It has been demonstrated that the vanilloid system plays an important role in inflammatory hyperalgesia. A study showed that the VR1 antagonist capsazepine (30 μg; i.pl.) prevented the thermal hyperalgesia induced by carrageenan in mice. [26] Capsaicin is currently available as topical ointments, as well as a high-dose dermal patch, which is to be applied for 30-60 minute every 90 days), to relieve the pain of peripheral neuropathy such as postherpetic neuralgia caused by shingles. It may be used as a cream for the temporary relief of minor aches and pains of muscles and joints associated with arthritis, simple backache, strains, and sprains, often in compounds with other rubefacients. The treatment typically involves the application of a topical anesthetic until the area is numb.

Intranasal capsaicin for cluster headache

It has been suggested that treatment of cluster headache (CH) patients with topical capsaicin may desensitize sensory neurons by depleting the nerve terminals of substance P. A study was conducted to investigate whether capsaicin is effective in aborting CH attacks. Patients suffering from acute CH were randomized to receive either capsaicin or placebo in the ipsilateral nostril for 1 week. Patients were instructed to record the severity of each headache for 15 days. Headaches on days 8-15 of the study were significantly less severe in the capsaicin group versus the placebo group. There was also a significant decrease in headache severity in the capsaicin group on days 8-15 compared to days 1-7, but not in the placebo group. Episodic CH patients appeared to benefit more than chronic CH patients. These results recommend intranasal capsaicin could be a new treatment strategy for the treatment of CH. However, further confirmatory studies are needed to investigate the efficacy of intranasal capsaicin in this disease. [27]

Capsaicin and postherpetic neuralgia

Two published studies [28],[29] compared topical capsaicin (0.075% cream) with placebo for the treatment of postherpetic neuralgia and reported a statistically significant improvement in the patients; experiencing pain relief from capsaicin cream as compared to placebo. Burning or stinging was the main adverse effect; this diminished after the first week with regular application of the cream. Both studies recommended that capsaicin should be applied four times daily. Capsaicin avoids problems with drug interactions and systemic toxicity; therefore, it is suggested that topical capsaicin be considered for initial management of postherpetic neuralgia.

Topical capsaicin for the treatment of chronic pain

Six double blind placebo controlled trials (656 patients) were conducted for analysis of relative benefit from topical capsaicin 0.075% compared with placebo in neuropathic conditions and three double blind placebo controlled trials (368 patients) were conducted for analysis of relative benefit from topical capsaicin 0.025% or plaster compared with placebo in musculoskeletal conditions. Recommendation from these studies is that topically applied capsaicin has moderate to poor efficacy in the treatment of chronic musculoskeletal or neuropathic pain, it may be useful as an adjunctive or sole therapy for a small number of patients who are unresponsive to, or intolerant of, other treatments. [30]

Topical capsaicin in the treatment of arthritis

Substance P has been implicated in the pathogenesis of inflammation and pain in arthritis. Capsaicin (a substance P depletor) was evaluated for treatment of osteoarthritis (OA) pain and with rheumatoid arthritis (RA) pain in a double-blind randomized study which included 70 patients of OA and 31 of RA. The patients were instructed to apply 0.025% capsaicin cream or its vehicle (placebo) to painful knees four times daily for 4 weeks. 80% of the capsaicin-treated patients in this study experienced a reduction in pain after 2 weeks of treatment. Transient burning at the sites of drug application was the major adverse effect reported by 23 of the 52 capsaicin-treated patients. Capsaicin cream is a safe and effective treatment for arthritis. [31]

Topical capsaicin cream in diabetic neuropathic pain

A double-blind, vehicle-controlled, multicentric study with parallel randomized treatment assignments trial conducted at 12 sites included 277 men and women with painful peripheral polyneuropathy and/or radiculopathy. Participants were unresponsive or intolerant to conventional therapy and were experiencing pain that interfered with functional activities and/or sleep. Either 0.075% capsaicin cream or vehicle cream was applied to the painful areas 4 times/day. The results of this study suggest that topical 0.075% capsaicin is effective for reducing pain in patients. [32]

EEG changes to skin pain and muscle pain induced by capsaicin

In a study by Chang et al., electroencephalogram EEG changes were compared produced by skin pain (induced by intracutaneous capsaicin) and muscle pain (induced by intramuscular capsaicin). It was observed that skin pain produces similar but not identical EEG topographic pattern as muscle pain evoked. However, muscle pain induced a significant beta-2 activity in the extensive frontal, parietal, and occipital areas compared to skin pain. [33]

A study was conducted to investigate the interactions between glutamate and capsaicin in inducing muscle pain and sensitization in humans in healthy volunteers. In this study, it was observed that intramuscular injection of glutamate and capsaicin interact and influence pain and sensitization to muscle nociceptors. Glutamate causes a sensitization to subsequent administration of capsaicin, whereas capsaicin is associated with desensitization to subsequent injection of glutamate. [34]

Capsaicin and euphoriant effect

People experiences pleasurable and euphoriant effects from eating capsaicin flavored foods. This is due to pain-stimulated release of endorphins. This effect can be blocked by compounds that compete opoid receptors sites with opoids and endorphins.

Axonal effects of capsaicin

Direct axonal application of capsaicin results in the excitation of both A -delta and C fibers which is followed by a nonspecific but reversible blockade of impulse propagation. [35]

Capsaicin and taste receptors

A study was conducted to evaluate the effects of capsaicin on K + current in taste receptors cells isolated from the rat circumvallate papilla. Observations from this study were that capsaicin directly inhibits K + current of the taste receptors cells and modify the gustatory sensation. [36]

The effects of transcranial magnetic stimulation on acute pain induced by capsaicin

A study was conducted to evaluate effects of 1-Hz repetitive transcranial magnetic stimulation on acute pain induced by capsaicin. In this study, it was observed that repetitive transcranial magnetic stimulation over M1 (primary motor cortex area) have beneficial effects on acute pain, and these effects are caused by functional changes of medial prefrontal cortex (MPFC), and caudal anterior cingulate cortex (ACC). [37]

Capsaicin and cardiovascular effects

Acute cardiac effect of capsaicin has been reported primarily as hypotension and bradycardia. Pure trans-capsaicin when delivered directly to systemic circulation at high dose levels in dogs is rapidly eliminated, induces transient tachycardia and hypertension, does not alters the duration of cardiac action potentials, and causes minimal organ toxicities. [38]

Capsaicin and tumors

Studies suggest that capsaicin by promoting apoptosis kills the prostate cancer cells and lung cancer cells. A study was performed on tumors formed by human prostate cancer cells culture grown in mouse models and showed that tumors treated with capsaicin were reduced to one-fifth of their original size. [39] Another studies conducted in Japan and China showed that capsaicin inhibits the growth of leukemic cancer cells. [40] Capsaicin at low concentration act as a CoQ1 mimic by protecting against rotenone induced ROS formation and mitochondrial membrane potential collapse. At higher concentration, capsaicin and CoQ1 became cytotoxic. The cytotoxic mechanism for both capsaicin and CoQ1 was shown to involve a collapse of the mitochondrial membrane potential, however only capsaicin causes ROS formation. [41] Another study conducted by Lo et al. suggested that capsaicin induces cell death in gastric adenomatous cells by promoting apoptosis via Bcl-2 sensitive pathway and is protective from gastric cancer. [42]


   Capsaicin and Gastrointestinal Tract Top


The effects of capsaicin on reflux, gastric emptying and dyspepsia and gastric ulcers

The effects of capsaicin were evaluated on heartburn, dyspepsia, gastric acidity and emptying, and gastro-esophageal reflux and the hypothesis that capsaicin induces heartburn and exacerbates symptoms by sensitizing the esophagus were investigated in a study conducted by Stanley et al., which showed that capsaicin enhances noxious postprandial heartburn, presumably by direct effects on sensory neurons. [43] Capsaicin decreases the gastric basal output, increases the non parietal (buffering) component of gastric secretory responses, gastric emptying, and release of glucagon. Capsaicin prevents the indomethacin- and ethanol-induced gastric mucosal injury, while capsaicin itself enhances the gastric transmucosal potential difference. Investigations carried out in recent years showed that chilli or its active principal "capsaicin" is not the cause of gastric ulcer; even capsaicin is helpful in preventing and healing of gastric ulcers by stimulating alkali, mucus secretions, and gastric mucosal blood flow. It acts by afferent neurons in the stomach and signals for protection against injury causing agents. Capsaicin exhibits gastric cytoprotection, essentially by stimulating sensory neurons, and this action is facilitated by endogenous prostaglandins through EP2/IP receptors, probably sensitizing the sensory neurons to capsaicin. [44]

Capsaicin increases intestinal absorption of cefazolin

The mechanism accounting for capsaicin-induced increase in intestinal cefazolin absorption is probably that capsaicin associated with increase TRPV1 increases intrinsic permeability of cefazolin in intestine. [45]

Capsaicin and respiratory system

Inhaled capsaicin in humans causes cough and transient increase in airways resistant by stimulation of sensory nerves in the airway. The induced cough can be modulated by using opoids and local anesthetics and the increase in airway resistance by anticholinergic agents. [46]

A study was conducted to evaluate the effects of enalapril and imidapril in the capsaicin cough challenge test and on spirometry. In this study, it was observed that neither enalapril nor imidapril significantly alters the capsaicin cough threshold. A small but significant reduction in forced expiratory volume in 1 second and forced vital capacity was recorded after enalapril treatment but not with imidapril treatment. [47]

Capsaicin and cystic fibrosis

Cystic fibrosis transmembrane conductance regulator (CFTR) is a transporter protein. Defective functioning of this transporter protein results in defective chloride transports across the various epithelial cells in different tissue such as respiratory, gastrointestinal, hepatobilliary, and reproductive tracts. Steatorrhea is resulted from deficiency of pancreatic enzymes, caused by defects of chloride transport in the intestinal epithelial cells which play important role in gastrointestinal symptoms in cystic fibrosis. [48] Tomohiko et al., conducted a study to investigate the effect of capsaicin on CFTR. In this study, wild-type and mutant CFTR chloride channel currents using patch-clamp methods were recorded. The effects of capsaicin were compared with genistein (a CFTR activator). It was observed that both capsaicin and genistein potentiate the c-AMP-stimulated G551D-CFTR, ∆ F508-CFTR, and 8SA mutant channel currents. Results of this study suggest that capsaicin and genistein may bind to a common binding site. The binding site for capsaicin is located at the cytoplasmic domain of CFTR. Capsaicin found to be partial agonist of genistein in activation of CFTR chloride channel. It was suggested that both of these compounds affects ATP dependent gating of CFTR. [49]

Antiplatelet effects of capsaicin

Capsaicin was studied by Wang et al. for its effects on platelets. In this study, it was observed that capsaicin had some membrane stabilizing properties which interfere with the activation of phospholipase A2. Capsaicin was found potent inhibitor of platelet aggregation and release reaction in rats. It inhibited the aggregation of rat platelet induced by collagen and thrombin, but only slightly reduced those caused by arachdionic acid. The IC 50 of capsaicin on collagen-induced platelet aggregation was recorded about 85 μg/ml. [50]

Capsaicin effect on blinking

A study was conducted to understand the effects of transdermally applied capsaicin on blinking. In this study, no effects of topical capsaicin were detected in eye blink rates in humans. However, when capsaicin was applied to a female subject with blepharospasm, it showed a dramatic restoration of her vision subsequent to blinking modification. Deactivation of abnormal A- to- C fibers crossed in the trigeminal -facial pathways thought to be the most likely mechanism of this improvement. [51]

Capsaicin and burning mouth syndrome

Burning mouth syndrome (BMS) could be considered as an expression of atypical facial pain. Systemic capsaicin is therapeutically effective for the short -term treatment of BMS but gastrointestinal toxicity limits its large-scale, long-term use. [52],[53]

Capsaicin sensitive nerve fibers and uterine contractility

In a study conducted by Klukovis et al., the role of capsaicin sensitive nerves in the modulation of neurogenic contraction was studied in nonpregnant and term pregnant rat uteri. It was observed that capsaicin-sensitive afferent nerves, by the release of sensory neuropeptides, significantly contribute to the modulation of uterine contractility both in nonpregnant and term pregnant rats. It is suggested that uterine sensory nerves activation may be part of a trigger mechanism leading to preterm contractions evoked by inflammation etc. [54]

Capsaicin in allergy and immunology

A study was conducted by Taylor-Clark et al., to investigate specifically the hypothesis that histamine and capsaicin activate the trigeminal sensory nerves innervating the guinea pig nasal mucosa. In this study guinea pig trigeminal neurons were assessed for their responses to histamine and capsaicin by studying changes in the intracellular free calcium concentration, and assessed for substance P immune-reactivity. Results of this study showed that most (about 60%) of the sensory neurons innervating the nasal mucosa did not express the neuropeptide substance P, including nearly all large-diameter neurons, but also a significant number of small-diameter neurons (presumably C-fiber neurons). [55]

Capsaicin in treatment fibromyalgia

The efficacy and safety of 0.025% capsaicin cream was evaluated as a treatment for the pain associated with primary fibromyalgia. Capsaicin-treated patients reported significantly less tenderness in the tender points than patients who received vehicle at week 4 (P=0.03). There were no statistically significant differences between groups in the visual analog scale for pain. A significant increase (P=0.02) in grip strength was noted at week 2 for the capsaicin-treated patients. The most common adverse effect attributable to capsaicin was transient burning or stinging at the application site. This study suggests that capsaicin cream may be a useful therapy for pain associated with primary fibromyalgia; however, additional confirmatory studies are needed. [56]

Capsaicin in treatment of psoriasis vulgaris

The effects of topically applied capsaicin (a known inhibitor of cutaneous vasodilatation) on moderate and severe psoriasis were evaluated in a double-blind study, which included patients with symmetrically distributed psoriatic lesions. Capsaicin was applied topically to one side of their body and an identical-appearing vehicle was applied to the other side of body for 6 weeks. After 3 and 6 weeks of treatment, patients were evaluated for the changes in scaling and erythema and overall improvement of the psoriasis. In this study, significantly greater overall improvement was observed on sides treated with capsaicin compared to sides treated with vehicle. Similarly, significantly a greater reduction in scaling and erythema was observed on the side of capsaicin application. Burning, stinging, itching, and redness of the skin were noted by nearly half of the patients on initial applications of study medication but diminished or vanished upon continued application. These results suggest that topical application of capsaicin may be a useful new approach in the treatment of psoriasis. [57] Capsaicin creams are available for use to treat psoriasis as an effective way to reduce itching and inflammation.

Capsaicin in pruritic psoriasis

Substance P has been implicated in the pathophysiology of psoriasis and pruritus. Topical capsaicin is a potent substance P depletor, were evaluated in a study for treatment of patients with pruritic psoriasis. This study showed that topically applied capsaicin is effective therapy for treating pruritic psoriasis. [58]

Capsaicin for the treatment of acute lipodermatosclerosis and lobular panniculitis

In the literature two case has been reported suffering from acute lipodermatosclerosis refractory to several conventional treatment regimens and one case of acute lobular panniculitis in a pregnant woman with venous insufficiency, were cured successfully within a short period of 3 weeks with topical 0.075% capsaicin cream. [59]

Skin and hepatic metabolism of capsaicin

In vitro metabolism of pure capsaicin was studied in a study, which showed that the metabolism of capsaicin was similar in humans, rats, and dog's microsome and S9 fractions. In these assays, 3 major metabolites were detected and identified as 16-hydroxyl capsaicin, 17-hydroxycapsaicin and 16,17-dehydroxycapsaicin. In addition to these three metabolites, rat microsome and S9 fractions also produced vanillylamine and vanillin. Biotransformation of capsaicin is slow in human skin in vitro, with the majority of applied capsaicin remaining unchanged and a small fraction is metabolized to vanillylamine and vanillic acid. Metabolism of capsaicin by cytochrome P 450 enzymes in skin is minimal relative to hepatic metabolism. [60]


   Conclusions Top


Capsaicin (A substance P depletor), by topical route, has given promising results in neuropathic pain, pain in musculoskeltal disorders, postherpetic neuralgia, pain due to fibromyalgia, psoriatic disorder, burning mouth syndrome, various allergic disorders, and intranasally for CH. Capsaicin has also shown promising results in preliminary studies for blepharo spasm, prostatic cancer, lung cancer, and various leukemias. It has also shown to be a cytoprotective agent for gastric cells in animal studies. Main adverse effects reported with topical therapy are burning and stinging at the site of application, which resolves spontaneously after few applications. Topical capsaicin avoids problem of systemic toxicity and drug interaction. However, studies with systemic capsaicin are limited. Capsaicin is underdevelopment drug for a number of diseases and may develop as initial treatment therapy for a number of diseases in near future time.

 
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