Author: erica galliano
Date: 11/09/2008


Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is an active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in any tissue with which it comes into contact. Capsaicin and several related compounds are called capsaicinoids and are produced as secondary metabolites by chili peppers, probably as deterrents against certain mammals and fungi

La capsaicina è l’alcaloide che conferisce sapore piccante ai peperoncini , appartiene alla famiglia dei capsacinoidi, è una molecola insolubile in acqua, solubile nell’alcol, idrofoba, incolore e inodore. La capsaicina non viene alterata dalla cottura, dal congelamento e dagli enzimi digestivi.

Meccanismo d’azione
la sensazione di bruciore e di dolore è data dal legame della capsaicina alle fibre amieliniche C e alle fibre mieliniche A delta dei neuroni sensoriali primitivi, la capsaicina si lega al recettore TRPV1, un canale per i cationi. In seguito al legame con la capsaicina il canale si apre ed entrano Sodio e Calcio, ne consegue la depolarizzazione e l’innesco di un potenziale d’azione.
Il legame della capsaicina alla terminazione nervosa sensitiva causa la liberazione di

  • sostanza P,
  • neurokinina A,
  • glutammato e
  • CGRP.

Questo meccanismo è alla base della sensazione di dolore e di bruciore, inoltre la sostanza P e il CGRP liberati dalla terminazione nervosa danno vasodilatazione e liberazione di istamina

i canali TRPV1

Il TRPV1 è un recettore canale che appartiene alla superfamiglia dei TRP ion channel (transient receptor potential).
Il canale TRPV1 è attivato da:
• capsaicina, in quanto molecola idrofoba, il suo sito di legame può trovarsi sia nella porzione intracellulare che extracellulare del recettore.
• Calore: 43° C
• pH< 6
dove si trovano
• Sono molto espressi dai gangli delle radici dorsali del midollo spinale
• Nel SNC si trovano nell’ippocampo e nell’ipotalamo

Desensibilizzazione dei neuroni: meccanismo alla base dell’analgesia
la prolungata o ripetuta applicazione della capsaicina porta ad una riduzione della capacità di trasmettere lo stimolo nocicettivo, dato non solo dalla capsaicina, ma anche da parte di altri stimoli nocicettivi.
La desensitizzazione farmacologica fa sì che il ripetuto stimolo con la capsaicina porti ad una progressiva riduzione della risposta.
La desensitizzazione funzionale: l’aumento del Ca dato dalla capsaicina attiva la calcineurina, una fosfatasi che defosforila il canale TRPV1 e altre proteine coinvolte nella trasmissione dello stimolo nocicettivo, tra cui VACCs (voltage-activated Ca2+ channels)
Il canale TRPV1 è regolato da processi di fosforilazione e defosforilazione. Quando il canale è fosforilato è più sensibile agli stimoli, quando è defosforilato lo è meno.

Dopo il trattamento con capsaicina lo stimolo nocicettivo non è seguito dal rilascio di trasmettitori. Il blocco del rilascio di trasmettitori inibirebbe la trasmissione del segnale nocicettivo tra i neuroni sensoriali e i neuroni del midollo spinale, inoltre ci sarebbe anche una riduzione della infiammazione neurogenica evocata dal rilascio di neuropeptidi da parte delle terminazioni periferiche.
Gli effetti analgesico e antinfiammatorio della capsacina sono limitati alle fibre sensibili alla capsaicina.
il danno è in parte osmotico, e in parte mediato dal calcio. L’aumento del Sodio comporta un richiamo di acqua e la lisi osmotica della cellula. L’aumento del Calcio comporta l’attivazione di proteasi calcio-dipendenti che distruggono la terminazione nervosa. La degenerazione nervosa può essere irreversibile

Calcium-dependent desensitization of vanilloid receptor TRPV1: a mechanism possibly involved in analgesia induced by topical application of capsaicin.

Functional changes in the vanilloid receptor subtype 1 channel during and after acute desensitization

2012-12-02T15:08:34 - Gianpiero Pescarmona

Cerotto alla Capsaicina

splo dolori post-erpetici?

  • multiple sclerosis
  • acufeni
2012-03-27T08:52:16 - martina gerbino


Hot chile peppers have been used as an alternative medicine for centuries. Although some chiles are quite hot, most are valued for their soothing effects on the digestive system, relief from symptoms of colds, sore throats and fevers, circulation, especially for cold hands and feet, and as a hangover remedie. Peppers can act as a heart stimulant which regulates blood flow and strengthens the arteries, possibly reducing heart attacks. Nutritionally, fresh chile peppers are an excellent source of calcium and vitamin C.
Medical use and health benefits of hot chili peppers
Capsaicin (trans-8-methyl-N-Vanilyl-6-nonenamide) is the pungent ingredient found in red pepper and hot chili pepper. It has principally been used as spice, food additive, as drugs. Capsaicin belongs to the plant genus Capsicum of family Solanaceae. Capsaicin activates TRPV1 a protein which in humans is encoded by the trpv1 gene.

Anti-carcinogenic properties

A number of phytochemicals present in medicinal plants are known to possess substantial anti-carcinogenic and anti-mutagenic activities. Capsaicin is a known phytochemical that preferentially repress the growth of various immortalized or malignant cell lines via induction of apoptosis.

Induction of apoptosis is in association with significant elevation of intracellular reactive oxygen species production in cells. Inhibitory effects of capsaicin on cancer development in multiple organs, such as, stomach, lung, and liver have been extensively documented.
These inhibitory effects of capsaicin on promoter through the inactivation of two defined eukaryotic transcription factors, nuclear factor-kappa β NF-kB, and activator protein 1 AP-1 have been reported.
Therefore, capsaicin suppresses TPA-stimulated activation of NF-kB through inhibition of IkBa degradation and blockade of the subsequent nuclear translocation of p65 in human promyelocytic leukemia HL-60 cells.

Mechanism of NF-κB action. In this figure, the NF-κB heterodimer between Rel and p50 proteins is used as an example. While in an inactivated state, NF-κB is located in the cytosol complexed with the inhibitory protein IκBα. Through the intermediacy of integral membrane receptors, a variety of extracellular signals can activate the enzyme IκB kinase(IKK). IKK, in turn, phosphorylates the IκBα protein, which results in ubiquitination, dissociation of IκBα from NF-κB, and eventual degradation of IκBα by the proteosome. The activated NF-κB is then translocated into the nucleus where it binds to specific sequences of DNA called response elements (RE). The DNA/NF-κB complex then recruits other proteins such as coactivators and RNA polymerase, which transcribe downstream DNA into mRNA, which, in turn, is translated into protein, which results in a change of cell function.

A Chinese study focused on the role of capsaicin in Human Leukemia
Capsaicin was shown to inhibit human HL-60 cells, through the induction of G0-G1 cell cycle arrest via the inhibition of cyclin E and the induction of apoptosis through the production of Ca2+ and activation of caspase-3.

Study results demonstrated that capsaicin induced apoptosis via the mitochondria-dependent pathway and promoted the expression of Bax and the release of cytochrome c as well as the activation of caspase-3, but decreased the levels of Bcl-2 in HL-60 cells.
Cytochrome c is released by the mitochondria in response to pro-apoptotic stimuli. The sustained elevation in calcium levels precedes cyt c release from the mitochondria. The release of small amounts of cyt c leads to an interaction with the IP3 receptor (IP3R) on the endoplasmic reticulum(ER), causing ER calcium release. The overall increase in calcium triggers a massive release of cyt c, which then acts in the positive feedback loop to maintain ER calcium release through the IP3Rs. This explains how the ER calcium release can reach cytotoxic levels. This release of cytochrome c in turn activates caspase 9, a cysteine protease. Caspase 9 can then go on to activate caspase 3 andcaspase 7, which are responsible for destroying the cell from within.

Involvement of Bax, Bcl-2, Ca2+ and Caspase-3 in Capsaicin induced Apoptosis of Human Leukemia HL-60 Cells

Another recent study reports that capsaicin has a profound antiproliferative effect on prostate cancer cells, inducing the apoptosis of both androgen receptor (AR)-positive (LNCaP) and -negative (PC-3, DU-145) prostate cancer cell lines associated with an increase of p53, p21, and Bax.
It demonstrates that this component of chili peppers provoked, approximately 80% of the prostate cancer cells to follow molecular mechanisms which lead to programmed cellular death (apoptosis).
It also slows down the growth of the prostate tumor through the regulation of the androgen receptors, the proteins activated by steroids which control the expression of certain genes associated with growth.

Capsaicin, a Component of Red Peppers, Inhibits the Growth of Androgen-Independent, p53 Mutant Prostate Cancer Cells

Capsaicin and H pylori

Nicolas L JONES demonstrate that capsaicin exerts a time- and concentration-dependent inhibition of the growth of H. pylori in vitro. The effect of capsaicin was specific for H. pylori as demonstrated by a lack of bactericidal activity against a nonpathogenic human commensal E. coli strain. In addition, capsaicin continued to exhibit antibacterial activity at reduced pH values suggesting that the efficacy of capsaicin could be independent of pH. Taken together, these findings imply that either capsaicin or chili peppers could have a therapeutic effect in H. pylori-associated disease by inhibiting the growth and colonization of the organism. The maximum inhibitory dose of capsaicin tested corresponds to 1 mg ml−1 of chili. This concentration is achievable through diet in populations with a high consumption of chili. For example, the per capita consumption of chili in India is 3 g per day . For cultures which do not ingest chili, capsaicin could be administered in capsule form. In addition, the time course of bactericidal activity in vitro is comparable to that of antimicrobial agents currently recommended for H. pylori eradication therapy . Taken together, these findings suggest that capsaicin holds promise as a nutritional agent in the treatment and prevention of H. pylori-induced gastrointestinal disease.

Growth of H. pylori strain LC 11 incubated with capsaicin (50 μg ml−1) over time. Results are expressed as a percentage of bacterial growth in the absence of capsaicin for the mean of two separate experiments. The absolute values for growth of H. pylori without capsaicin were 1.3×106, 3.9×107, and 8.0×107 cfu at times 1, 4, and 6 h.
Capsaicin as an inhibitor of the growth of the gastric pathogenHelicobacter pylori


Capsaicin cream or gel is used to help control neuropathic pain (numbness, tingling, burning, shooting, or electric-shock-like pain), such as post-herpetic neuralgia (pain in areas affected by shingles). You can buy creams or gels over the counter, without a prescription. The capsaicin patch is more potent, and requires a prescription.

TRPV1maybe a novel target for pharmacological treatment of chronic pain states associated with bone cancer metastasis.
A recent study demonstrates that acute or chronic administration of a TRPV1 antagonist or disruption of the TRPV1 gene results in a significant attenuation of both ongoing and movement-evoked nocifensive behaviors. Administration of the antagonist had similar efficacy in reducing early, moderate, and severe pain-related responses.

Malignant bone tumors occur in patients with primary bone cancer but far more commonly occur as distant metastases of nonbone primary tumors, notably those in breast, prostate, and lung.
As such, bone is the most common site of origin of chronic pain in patients with metastatic lung, prostate, and breast cancers or myeloma.

TRPV1in animals show impaired thermal hypersensitivity in response to tissue inflammation, supporting the idea that TRPV1 serves as a detector of injury-induced chemical stimuli that excite primary afferent nociceptors or sensitize their response to heat.

TRPV1 channel plays a role in the integration of nociceptive signaling in a severe pain state and
that antagonists of TRPV1 may be effective in attenuating difficult-to-treat mixed chronic pain states, such as those encountered in patients with bone cancer pain.
The ability of a TRPV1 antagonist to maintain its analgesic potency with disease progression is probably influenced by the fact that sensory nerve fibers innervating the tumor-bearing mouse femur maintain their expression of TRPV1 even as tumor growth and tumorinduced bone destruction progresses.

Selective Blockade of the Capsaicin Receptor TRPV1 Attenuates Bone Cancer Pain

2012-02-19T10:21:55 - Giacomo Vallome

Role of TRPV1 and capsaicin in diabetes and obesity

The transient receptor potential cation channel subfamily vanilloid member 1 (TRPV1), also known as the capsaicin receptor, is a protein that, in humans, is encoded by the TRPV1 gene. It was the first isolated member of the transient receptor potential vanilloid receptor proteins which in turn are a sub family of the transient receptor potential protein group. This protein is a member of the TRPV group of transient receptor potential family of ion channels.

Capsaicin activates TRPV1, and, upon prolonged application TRPV1 activity, would decrease (desensitization), leading to alleviation of pain. Agonist can be applied locally to the painful area as through a patch or an ointment. Numerous capsaicin-containing creams are available over the counter, containing low concentrations of capsaicin (0.025 – 0.075%). 8% capsaicin patches have recently become available for clinical use, with supporting evidence demonstrating that a 30 minute treatment can provide up to 3 months analgesia by causing regression of TRPV1 containing neurones in the skin.

Capsaicin is the active component of chili peppers, which are plants belonging to the genus Capsicum. It is an irritant for mammals, including humans, and produces a sensation of burning in anytissue with which it comes into contact. Capsaicin and several related compounds are called capsaicinoids and are produced as a secondary metaboliteby chili peppers, probably as deterrents against certain herbivores and fungi. Pure capsaicin is a hydrophobic, colorless, odorless, crystalline to waxy compound.

The capsaicin receptor transient receptor potential vanilloid subfamily member 1 (TRPV1) is highly expressed on sensory nerve fibers innervating the pancreas. Indeed, the role of TRPV1 in mediating pain during pancreatitis is well established.
The initial excitation of these nerves by capsaicin is followed by a reversible refractory state (desensitization) or, under certain conditions (such as neonatal treatment), neurotoxicity. Ablation of TRPV1-positive fibers, by subcutaneous capsaicin treatment, not only ameliorates pancreatitis pain but also diminishes aging-associated weight gain and improves glucose tolerance both in mice on a high-fat diet and in rat models of type 2 diabetes. New evidence implies an unexpectedl role for TRPV1 in type 1 (autoimmune) diabetes. Non-obese diabetic (NOD) mice carry a hypofunctional TRPV1 mutant. Ablation of nerves carrying this mutant TRPV1 by capsaicin prevents immune-mediated destruction of islet beta cells despite the persistence of diabetogenic T cells. Collectively, these findings establish a crucial link among sensory nerves, obesity and diabetes and identify pharmacological TRPV1 blockade as a novel therapeutic approach for diabetes prevention and weight control.
Obesity-induced inflammation contributes to the development of obesity-related metabolic disorders such as insulin resistance, type 2 diabetes, fatty liver disease, and cardiovascular disease.  Dietary capsaicin may reduce obesity-induced glucose intolerance by not only suppressing inflammatory responses but also enhancing fatty acid oxidation in adipose tissue and/or liver, both of which are important peripheral tissues affecting insulin resistance. The effects of capsaicin in adipose tissue and liver are related to its TRPV1 expression/activation (and expression/activation of another receptor).

The emerging role of TRPV1 in diabetes and obesity. (2008)

Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. (2010)

Type 1 diabetes

Non-obese diabetic or NOD mice are used as an animal model for type 1 diabetes. Diabetes develops in NOD mice as a result of insulitis, a leukocytic infiltrate of the pancreatic islets. Onset of diabetes is associated with a moderate glycosuria and a non-fasting hyperglycaemia.  Onset of diabetes also varies between males and females: commonly, onset is delayed in males by several weeks.
Type 1 diabetes is a form of diabetes mellitus that results from autoimmunedestruction of insulin-producing beta cells of the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose. The classical symptoms are polyuria (frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss.
In type 1 diabetes, insulin deficiency is produced by T cell-mediated death of pancreatic beta cells. TRPV1 pancreatic sensory neurons control islet inflammation and insulin resistance. Eliminating these neurons in diabetes-prone NOD mice prevents insulitis and diabetes, despite systemic persistence of pathogenic T cell pools. Insulin resistance and beta cell stress of prediabetic NOD mice are prevented when TRPV1 neurons are eliminated. TRPV1 mediates depressed neurogenic inflammation. Concordantly, insulin sensitivity is enhanced in TRPV1 (-/-) mice, whereas insulitis/diabetes-resistant mice, carrying wild-type TRPV1, show restored TRPV1 function and insulin sensitivity. So, there is a fundamental role for insulin-responsive TRPV1 sensory neurons in beta cell function and diabetes pathoetiology.

TRPV1+ sensory neurons control beta cell stress and islet inflammation in autoimmune diabetes. (2006)

Type 2 diabetes

The Zucker Diabetic Fatty (ZDF) rat is a popular obese, type 2 diabetes research model. They're also used in researches about hyperlipidemia, glucose intolerance, obesity and hyperinsulinemia.
Type 2 diabetes is a metabolic disorder that is characterized by high blood glucose, in the context of insulin resistance and relative insulin deficiency. The classic symptoms are excess thirst, frequently having to urinate, and constant hunger. Type 2 diabetes makes up about 90% of cases of diabetes. Obesity is the primary cause of type 2 diabetes in people who are genetically predisposed to the disease.
The system that regulates insulin secretion from beta-cells in the islet of Langerhans has a capsaicin-sensitive inhibitory component. This component is probably the islet-innervating sensory fibers. Systemic capsaicin application before the development of hyperglycemia prevents the increase of fasting, non-fasting, and mean 24-h plasma glucose levels, and the deterioration of glucose tolerance assessed on the fifth week following the injection. These effects were accompanied by enhanced insulin secretion and a TRPV1-coexpressing islet-innervating fibers. Elimination of these fibers contributes to the prevention of the deterioration of glucose homeostasis, through increased insulin secretion in Zucker Diabetic Fatty rats. The activity of islet-innervating capsaicin-sensitive fibers may have a role in the development of reduced insulin secretion in human type 2 diabetes mellitus.

Capsaicin-sensitive sensory fibers in the islets of Langerhans contribute to defective insulin secretion in Zucker diabetic rat, an animal model for some aspects of human type 2 diabetes. (2007)


Activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. In vitro, theTRPV1 agonist capsaicin dose-dependently induced calcium influx and prevented the adipogenesis in stimulated preadipocytes. RNA interference knockdown of TRPV1 in preadipocytes attenuated capsaicin-induced calcium influx, and adipogenesis in stimulated preadipocytes was no longer prevented.
During regular adipogenesis TRPV1 channels were downregulated which was accompanied by a significant and time-dependent reduction of calcium influx. Compared with lean counterparts in visceral adipose tissue from obese mice, and from obese human male subjects we observed a reduced TRVP1 expression. The reduced TRPV1 expression in visceral adipose tissue from obese humans was accompanied by reduced capsaicin-induced calcium influx. The oral administration of capsaicin for 120 days prevented obesity in male wild type mice but not in TRPV1 knockout mice assigned to high fat diet. So, the activation of TRPV1 channels by capsaicin prevented adipogenesis and obesity.
There is also another mechanism of capsaicin protection against obesity. Metabolic dysregulation (e.g., hyperglycemia, hyperinsulinemia, hyperlipidemia, etc.) is a sign of obesity-related diseases such as insulin resistance, type 2 diabetes, and fatty liver disease.
Adiponectin is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism. Adiponectin is exclusively secreted from adipose tissue into the bloodstream and is very abundant in plasma relative to many hormones. Levels of the hormone are inversely correlated with body fat percentage in adults .
Dietary capsaicin reduces metabolic dysregulation in obese/diabetic mice by enhancing expression of adiponectin and its receptor. Capsaicin may be useful as a dietary factor for reducing obesity-related metabolic dysregulation.

Activation of transient receptor potential vanilloid type-1 channel prevents adipogenesis and obesity. (2007)

Dietary capsaicin attenuates metabolic dysregulation in genetically obese diabetic mice. (2011)

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