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PubMed1986

Capsaicin-sensitive afferent neurones and gastrointestinal propulsion in the rat.

Gastrointestinal propulsion (gastric emptying and gastrointestinal transit) of a test meal containing charcoal and 51Cr as well as defaecation in relation to food intake were studied in adult rats pretreated with capsaicin (0.40 mmol kg-1 S.C.) or its solvent one week before experimentation. In solvent-treated rats, gastrointestinal propulsion did not differ when the test meal was given to conscious animals or when the meal was administered under ether anaesthesia. In rats treated with capsaicin, gastrointestinal propulsion was unchanged as compared with solvent-treated rats when the test meal was administered to conscious animals. When, however, the meal was given under ether anaesthesia capsaicin-treated rats showed a delayed gastrointestinal propulsion as compared with solvent-treated rats. This delay in gastrointestinal propulsion was abolished by pretreatment of the animals with guanethidine (67 mumol kg-1 S.C.). Rats treated with capsaicin exhibited a prolonged sleeping time in response to ether as compared with solvent-treated rats. Defaecation in relation to food intake was not changed in rats treated with capsaicin as compared with solvent-treated animals. These results indicate that capsaicin-sensitive afferent neurones do not participate in the physiologic control of gastrointestinal propulsion. The delay in gastrointestinal propulsion observed in capsaicin-treated rats when fed under ether anaesthesia seems to involve the sympathetic nervous system. This finding suggests that secondary functional changes in the autonomic nervous system following capsaicin treatment can influence physiologic processes in which capsaicin-sensitive afferent neurones are not primarily implicated.

Anesthesia↗
PubMed1985

Evidence for a capsaicin-sensitive vasomotor mechanism in the ventral medullary chemosensitive area of the cat.

The effects of capsaicin applied to the exposed ventral surface of the medulla were studied on the mean arterial blood pressure, heart rate, respiration and sympathetic efferent nerve activity in chloralose-urethane-anaesthetized cats. The application of capsaicin produced a marked increase in the mean arterial blood pressure and sympathetic nerve activity, but not in the heart rate. The "intermediate area" proved to be the most sensitive to capsaicin. Pressor responses could be elicited repeatedly; tachyphylaxis was not noted provided a time interval of 30 min elapsed between consecutive applications. Repeated applications of capsaicin at intervals of less than 30 min led to tachyphylaxis. However, pressor responses evoked by either topical application of glutamate or pentamethylene-tetrazole or bilateral carotid occlusion could invariably be demonstrated during this period of tachyphylaxis. Histological studies revealed the existence of a hitherto unrecognized termination of capsaicin-sensitive nerve endings within the ventral medullary chemosensitive area of the cat. The results provide both functional and morphological evidence for the presence of a capsaicin-sensitive vasomotor mechanism in the ventral medullary chemo-sensitive area of the cat. It is suggested that the pressor effects of capsaicin applied to the ventral medullary chemo-sensitive area may be mediated by an activation of capsaicin-sensitive primary sensory afferents terminating in this area. Accordingly, capsaicin-sensitive neuronal mechanisms located in the ventral medullary chemosensitive area may play an important role in the central nervous regulation of blood pressure.

Animals↗
PubMed1996

Influence of capsaicin-sensitive afferent neurons and nitric oxide (NO) on cerulein-induced pancreatitis in rats.

CONCLUSION: Stimulation of afferent neurons by capsaicin exerts protective activity against cerulein-induced pancreatitis. This action is dependent on endogenous release of nitric oxide (NO). Deactivation of afferent neurons by high doses of capsaicin contributes to the severity of pancreatitis. This action involves mainly decreased pancreatic blood flow (PBF). Afferent nerves and NO cooperate in the maintenance of the integrity of pancreatic tissue. BACKGROUND: Stimulation of capsaicin-sensitive afferent fibers protects gastric mucosa against damage and causes changes in mucosal blood flow. The aim of the present study was to determine the role of stimulation or ablation of capsaicin-sensitive neurons and NO in the course of cerulein-induced pancreatitis in the rat. METHODS: Low and high doses of capsaicin were administered to animals with pancreatitis and to those without pancreatitis. The effect of several parameters was assessed. NO activity was blocked by NG-nitro-L-arginine. RESULTS: We found that a low dose of capsaicin administered intragastrically caused an increase in PBF. A neurotoxic dose of capsaicin caused a decrease in PBF, RNA content, and DNA synthesis. Pancreatitis led to a significant decrease in PBF and DNA synthesis, but an increase in pancreatic weight, protein content, plasma amylase concentration, and neutrophil adherence. Stimulatory doses of capsaicin attenuated the pancreatic tissue damage of pancreatitis, and alteration of PBF, DNA synthesis, and neutrophil adherence. Capsaicin-induced ablation of afferent neurons caused an increase in all indicators of pancreatic damage. Blocking NO enhanced pancreatic damage, and this was reversed by addition of L-arginine.

Animals↗
PubMed2005

A phospholipase C-dependent intracellular Ca2+ release pathway mediates the capsaicin-induced apoptosis in HepG2 human hepatoma cells.

The effect of capsaicin on apoptotic cell death was investigated in HepG2 human hepatoma cells. Capsaicin induced apoptosis in time- and dose-dependent manners. Capsaicin induced a rapid and sustained increase in intracellular Ca2+ concentration, and BAPTA, an intracellular Ca2+ chelator, significantly inhibited capsaicin-induced apoptosis. The capsaicin-induced increase in the intracellular Ca2+ and apoptosis were not significantly affected by the extracellular Ca2+ chelation with EGTA, whereas blockers of intracellular Ca2+ release (dantrolene) and phospholipase C inhibitors, U-73122 and manoalide, profoundly reduced the capsaicin effects. Interestingly, treatment with the vanilloid receptor antagonist, capsazepine, did not inhibit either the increased capsaicin-induced Ca2+ or apoptosis. Collectively, these results suggest that the capsaicin-induced apoptosis in the HepG2 cells may result from the activation of a PLC-dependent intracellular Ca2+ release pathway, and it is further suggested that capsaicin may be valuable for the therapeutic intervention of human hepatomas.

Apoptosis↗
PubMed2002

Nitric oxide is involved in the relaxant effect of capsaicin in the human sigmoid colon circular muscle.

The relaxant effect of capsaicin (300 nM) has been studied on mucosa-free circular strips of the human sigmoid colon in vitro. The response of precontracted preparations to capsaicin (sub-maximal relaxation) was reduced by over 50% by the nitric oxide synthase inhibitor N(G)-nitro- L-arginine (L-NOARG; 20 microM or 100 microM) or by the guanylate cyclase inhibitor 1 H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 1 microM), but not by tetrodotoxin (1 microM) or the P(2) purinoceptor antagonist pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid (PPADS; 50 microM). L-NOARG or ODQ caused moderate contraction of the circular muscle, indicating a tonic "nitrergic" control. Anandamide (1-100 microM), an endogenous cannabinoid and capsaicin VR(1) receptor stimulant, failed to either mimic or modify the response to capsaicin (300 nM). It is proposed that capsaicin causes the release of smooth muscle relaxant substance(s) from afferent nerve endings in the gut wall, in a tetrodotoxin-resistant manner. Nitric oxide (possibly released from capsaicin-sensitive afferents) plays an important role in the capsaicin-evoked response. No evidence has been found for an involvement of PPADS-sensitive P(2) purinoceptors in the response to capsaicin or for a stimulation or inhibition of capsaicin-sensitive receptors by anandamide in the human sigmoid colon.

Arachidonic Acids↗
PubMed2001

Pro- and anti-inflammatory actions of ricinoleic acid: similarities and differences with capsaicin.

We have investigated the pro- and anti-inflammatory effects of ricinoleic acid (RA), the main active principle of castor oil, in an experimental model of blepharitis induced by intradermal injection of carrageenan in the guinea-pig eyelid and its possible capsaicin-like mode of action on acutely dissociated rat dorsal root ganglia (DRG) neurons in vitro. Topical treatment with RA (10-100 mg/guinea-pig) or capsaicin (1-10 mg/guinea-pig) caused eyelid reddening and oedema. At lower doses (0.3-3 mg/guinea-pig and 0.009-0.09 mg/guinea-pig for RA and capsaicin, respectively) both drugs significantly potentiated the eyelid oedema induced by carrageenan. The tachykinin NK1 receptor antagonist FK 888 (0.59 mg/kg s.c.) abolished the potentiation of carrageenan-induced eyelid oedema induced by either RA or capsaicin. The neutral endopeptidase inhibitor, thiorphan (1.3 mg/kg i.v.) significantly enhanced the potentiation of carrageenan-induced eyelid oedema produced by RA. This potentiating effect was abolished by FK 888. Repeated (8 days) topical application of RA (0.9 mg/guinea-pig) or capsaicin (0.09 mg/guinea-pig) inhibited the carrageenan-induced eyelid oedema. This anti-inflammatory effect was accompanied by a reduction (75%-80% of SP and 46%-51% of NKA) in tachykinin content of the eyelids, as determined by radioimmunoassay. In dissociated rat DRG neurons, RA (0.1 mM for 5 min) significantly inhibited the inward currents induced by application of capsaicin (1 microM) and/or low pH (5.8), without inducing any currents by itself or changing voltage-dependent currents. Moreover, after 24-h incubation, RA (0.1 mM) significantly decreased the capsaicin (1 microM)-induced calcitonin gene-related peptide (CGRP) release from rat DRG neurons, whereas acute drug superfusion did not evoke CGRP release by itself. Summarizing, RA possesses capsaicin-like dual pro-inflammatory and anti-inflammatory properties which are observed upon acute and repeated application, respectively. However, unlike capsaicin, RA does not induce inward current in DRG neurons and it is devoid of algesic properties in vivo.

Animals↗
PubMed2005

Inhibitory effect of capsaicin evoked trigeminal pain on warmth sensation and warmth evoked potentials.

The aim of the study was to evaluate the effect of tonic pain evoked by topical application of capsaicin on the somatosensory sensation of warmth. The warmth pathways were studied in ten healthy subjects by recording the scalp potentials evoked by non-painful warm laser stimuli delivered on both the right and left perioral region (warmth C-fiber related laser-evoked potentials (C-LEPs)). Tonic pain was induced by topical capsaicin application above the lateral part of the right upper lip. The area of primary and secondary hyperalgesia were mapped. C-LEPs were obtained from 31 scalp electrodes before, during, and after capsaicin application. C-LEPs from the right perioral region were evoked by laser stimuli delivered to the area of secondary hyperalgesia during capsaicin application and on both the areas of primary and secondary hyperalgesia after capsaicin removal. While the lateralized N1/P1 component (around 185 ms of latency) was not affected by the capsaicin, the amplitudes of the later vertex C-LEPs (around 260 and 410 ms of latency for the N2a and P2 potentials, respectively) evoked from the secondary hyperalgesic area on the right side and from a symmetrical non-hyperalgesic area on the left perioral region were significantly decreased during capsaicin application and after capsaicin removal, as compared with the baseline recordings. At the same times, the rating of the laser-evoked warmth sensation was reduced significantly. This inhibitory effect can occur at brainstem level and is possibly due to: 1) trigemino-cortico-trigeminal circuits, similar to those mediating the classical diffuse noxious inhibitory control, or 2) an increased background activity of the capsaicin-insensitive A-fibers, which mediate the secondary hyperalgesia. Probably due to a peripheral inhibitory mechanism, neither reliable C-LEP components nor warmth sensation were evoked by laser pulses delivered to the primary hyperalgesic area. This is the first neurophysiological evidence in humans of an inhibitory effect of pain on warmth sensation.

Adult↗
PubMed1995

Capsaicin affects the structure and phase organization of phospholipid membranes.

Capsaicin is a natural compound with pharmacological and toxicological effects, which given its hydrophobicity, can influence the structure of membranes. The interaction of capsaicin with model membranes of dipalmitoylphosphatidylcholine and dielaidoylphosphatidylethanolamine has been studied by using differential scanning calorimetry, fluorescent probe spectroscopy and 31P-nuclear magnetic resonance. Capsaicin remarkably affects the phase transition of dipalmitoylphosphatidylcholine, shifting the transition temperature to lower values, and giving rise, at relatively high capsaicin concentrations, to the appearance of two peaks in the thermogram. These peaks may correspond to separated phases as indicated by the partial phase diagram. Whereas capsaicin did not affect the fluorescence polarization of the probes diphenylhexatriene and trimethylammonium-diphenylhexatriene, it clearly affected that of the probe 2-anthroyloxystearic acid, indicating that the perturbation produced by capsaicin on the membrane would be mainly at the position where this fluorophore is located. On the other hand, capsaicin, at relatively low concentrations, gives rise to immiscible phases in the presence of dielaidoylphosphatidylethanolamine and decrease the temperature of the lamellar to hexagonal HII phase transition. At concentrations of capsaicin higher than 0.3 mol fraction, isotropic phases were detected. The possible implications of the effects of capsaicin on biological membranes are discussed.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Neuropharmacological mechanisms of capsaicin and related substances.

Capsaicin activates poorly myelinated primary afferent neurons, many of which are polymodal nociceptors. Activation is accompanied by membrane depolarization and the opening of a unique, cation-selective, ion channel which can be blocked by the polyvalent dye ruthenium red. The capsaicin-induced activation is mimicked by resiniferatoxin, a potent analogue, and by low pH. Activation is mediated by a specific membrane receptor which can be selectively and competitively antagonized by capsazepine. Repetitive administration of capsaicin produces a desensitization and an inactivation of sensory neurons. Several mechanisms are involved including receptor inactivation, block of voltage activated calcium channels, intracellular accumulation of ions leading to osmotic changes, and activation of proteolytic enzyme processes. Systemic and topical capsaicin produces a reversible antinociceptive and anti-inflammatory action after an initial undesirable algesic effect. Capsaicin analogues, such as olvanil, have similar properties with minimal initial algesic activity. Antinociception produced by capsaicin does not involve neurotoxicity, sensory neuropeptide depletion or activity at peripheral receptors; rather, systemic capsaicin produces antinociception by activating capsaicin receptors on afferent nerve terminals in the spinal cord. Spinal neurotransmission is blocked by a prolonged inactivation of sensory neurotransmitter release. However, local or topical applications of capsaicin block C-fibre conduction and inactive neuropeptide release from peripheral nerve endings. These mechanisms account for localized antinociception and the reduction of neurogenic inflammation, respectively.

Animals↗
PubMed1984

Cutaneous inputs to dorsal horn neurones in adult rats treated at birth with capsaicin.

Single unit electrical activity has been recorded from dorsal horn neurones in the lumbar spinal cord of adult rats which had been treated at birth with either capsaicin (50 mg kg-1) or with the solvent-vehicle only. The responses of these neurones to electrical stimulation of A- and C-fibres in the sural nerve and to natural stimulation of their cutaneous receptive fields have been studied. In vehicle-injected rats, 54% of the units driven by electrical stimulation of the A-fibres in the sural nerve could also be driven by stimulation of the C-fibres in this nerve. In capsaicin-treated animals, only 30% of such units had a C-fibre input from the sural nerve. In vehicle-injected rats, 51.5% of the neurones with a C-fibre input showed a 'wind-up' effect on repetitive C-fibre stimulation of the sural nerve at 1 Hz. A similar proportion of neurones (55%) displayed this effect in capsaicin-treated rats. There were fewer neurones with very intense 'wind-up' in capsaicin-treated compared to vehicle-treated rats. In capsaicin-treated animals, greater proportions of neurones with 'wind-up' were superficially located in the dorsal horn, had small receptive fields and were driven only by cutaneous nociceptors. The proportions of neurones driven by innocuous mechanical stimulation of the skin, by noxious mechanical stimulation or by both forms of stimulation were similar in vehicle-injected and capsaicin-treated animals. In capsaicin-treated rats, more neurones had 'medium-sized' receptive fields than in vehicle-injected rats. In capsaicin-treated rats, more neurones had receptive fields in the foot and ankle than in vehicle-injected animals, where receptive fields in the toes were predominant. Some neurones showed expanded receptive fields after repetitive electrical stimulation of C-fibres at 1 Hz. This expansion occurred more often in neurones recorded from capsaicin-treated animals than in those of vehicle-injected rats. These results are discussed in relation to the role of afferent C-fibres in sensory mechanisms.

Afferent Pathways↗
PubMed1990

Capsaicin desensitization in vivo is inhibited by ruthenium red.

The effect of systemic administration of Ruthenium Red on the excitatory and desensitizing effect of capsaicin was investigated in rats. Ruthenium Red was injected s.c. 30 min before capsaicin was administered. The excitatory effect of capsaicin on corneal, perivascular and visceral afferents was not influenced by treatment with Ruthenium Red. However, determination of the neuropeptide content and evoked neuropeptide release in peripheral organs and dorsal spinal cord 48 h after treatment showed that Ruthenium Red attenuated the 'desensitizing' effect of capsaicin at peripheral, but not at central, endings of primary afferents. On the other hand, a capsaicin-elicited autonomic reflex mediated by visceral afferents was still obtained in 9 of 14 rats that had received Ruthenium Red and capsaicin. The results indicate that a single dose of Ruthenium Red, which does not reduce the acute excitatory effect of capsaicin, reduces the desensitizing effect of capsaicin on peripheral endings of primary afferents in vivo. This long-lasting protective effect of Ruthenium Red suggests that it is possible to pharmacologically differentiate between the acute and chronic effects of capsaicin.

Animals↗
PubMed1990

Inhibitory effect of capsaicin on the ascending pathway of the guinea-pig ileum and antagonism of this effect by ruthenium red.

A segment of guinea-pig ileum, which was continuous with a strip of longitudinal muscle-myenteric plexus (LM-MP) at the anal end, was used to examine the effect of capsaicin on ascending excitatory pathways. Electrical field stimulation of the LM-MP caused an ascending contraction of the segment. After initially causing contraction capsaicin (3 microM) inhibited the ascending contraction. This inhibitory effect of capsaicin exhibited rapid desensitization and was abolished after extrinsic (mesenteric) denervation. Desensitization to calcitonin gene-related peptide (CGRP) prevented the capsaicin-induced inhibition without affecting the ascending contraction. Neither naloxone nor alpha- and beta-adrenoceptor antagonists affected the capsaicin-induced inhibition. CGRP (25 nM) also inhibited the ascending contraction, mimicking the inhibition induced by capsaicin. Ruthenium red (0.1-3 microM) antagonized the capsaicin-induced inhibition in a concentration-related manner, but did not affect the CGRP-induced inhibition. These findings suggest that the inhibitory effect of capsaicin on the ascending pathways might be mediated via the release of CGRP from extrinsic nerve terminals, and that the site of the antagonism of the action of capsaicin by ruthenium red is prejunctional.

Animals↗
PubMed1989

Release of substance P- and calcitonin gene-related peptide-like immunoreactivity and motor response of the isolated guinea pig gallbladder to capsaicin.

The aim of this study was to assess whether a local motor response to capsaicin could be observed in the isolated guinea pig gallbladder and to discover the mechanism involved. Capsaicin produced a contraction of this organ that exhibited desensitization, suggesting a specific action on sensory nerves. In preparations preexposed to capsaicin to produce a functional blockade of the capsaicin-sensitive sensory fibers, the contractile response to field stimulation was unaffected as compared with controls. Tachykinins (substance P and neurokinin A) produced a concentration-related contraction of this organ, neurokinin A being more potent than substance P. Spantide, a tachykinin antagonist, markedly inhibited the capsaicin-induced gallbladder contraction, leaving the atropine-sensitive response to field stimulation unaffected. Calcitonin gene-related peptide (CGRP) produced a concentration-related relaxation, which was tetrodotoxin-resistant, suggesting a direct effect on muscle cells. Repeated administration of CGRP produced desensitization. At this stage, application of capsaicin produced a contractile response much larger than in controls. Both substance P- and CGRP-like immunoreactivity were detected in the guinea pig gallbladder by radioimmunoassay and were significantly reduced after systemic capsaicin desensitization. Capsaicin induced the simultaneous release of substance P- and CGRP-like immunoreactivity from superfused isolated gallbladders. These findings indicate that capsaicin-sensitive nerves in the guinea pig gallbladder can produce a local motor response involving the release of multiple neuropeptides. In the guinea pig gallbladder, tachykinins and CGRP might act as "physiologic antagonists," as observed in other viscera from rats and guinea pigs.

Animals↗
PubMed1995

Intragastric capsaicin stimulates colonic motility via a neural reflex in conscious dogs.

BACKGROUND & AIMS: Capsaicin is known to contract smooth muscles and to have an excitatory action on thin, primary afferent neurons. The aim of this study was to test the hypothesis that intragastric capsaicin may have an excitatory effect on colonic motility. METHODS: Mongrel dogs equipped with five strain-gauge force transducers on the colon (C1-C5) were used. In 5 dogs, the effect of intragastric capsaicin (0.05, 0.1, 0.3, and 0.5 mg/kg) on colonic motility in the presence or absence of the cholinergic blockers atropine and hexamethonium was studied. In 4 dogs, the effect of capsaicin (0.5 mg/kg) administration into a vagally innervated or denervated gastric pouch on colonic motility was investigated. RESULTS: Motility at C2-C3, C1-C3, and C1-C5 was significantly increased by 0.1, 0.3, and 0.5 mg/kg of capsaicin, respectively. The excitatory effect of capsaicin on colonic motility was inhibited by atropine and hexamethonium. Colonic motility at C1-C4 was significantly increased by capsaicin administration into a vagally innervated pouch but was not affected by capsaicin administration into a vagally denervated pouch. CONCLUSIONS: These results indicate that intragastric capsaicin predominantly stimulates motility in the proximal half of the colon through neural pathways, probably through a vagovagal reflex, but sympathetic involvement cannot be excluded.

Animals↗
PubMed1995

Capsaicin, a double-edged sword: toxicity, metabolism, and chemopreventive potential.

Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a primary pungent and irritating principle present in chilies and red peppers which are widely used as spices. Because of its selective effects on the functions of a defined subpopulation of sensory neurons, capsaicin is currently used as a versatile tool for the study of pain mechanisms and also for pharmacotherapy to treat several pain disorders. Considering the frequent consumption of capsaicin as a food additive and its current medicinal use, correct assessment of hazardous effects of this compound is important. Mutagenic and carcinogenic activities of capsaicin and chili extracts have been studied, but results are conflicting. Mammalian metabolism of capsaicin has been also reported. Capsaicin appears to interact with xenobiotic metabolizing enzymes, particularly microsomal cytochrome P450-dependent monooxygenases which are involved in activation as well as detoxification of various chemical carcinogens and mutagens. Recent studies have shown that hepatic cytochrome P450 2E1 catalyzes the conversion of capsaicin to reactive species such as the phenoxy radical intermediate capable of covalently binding to the active site of the enzyme as well as tissue macromolecules. While covalent modification of protein and nucleic acids leads to toxicity including necrosis, mutagenesis, and carcinogenesis, suicidal inhibition of microsomal cytochrome P450 may prohibit further activation of capsaicin and also of other toxic xenobiotics. Results from recent studies indicate that capsaicin possesses the chemoprotective activity against some chemical carcinogens and mutagens.

Animals↗
PubMed1996

Capsaicin-induced biphasic oxygen uptake in rat muscle: antagonism by capsazepine and ruthenium red provides further evidence for peripheral vanilloid receptor subtypes (VN1/VN2).

Previous studies with the vanilloid spice principle capsaicin have demonstrated a biphasic VO2 response, with vasoconstriction, in the perfused rat hindlimb that has led to suggestions of vanilloid receptor subtypes (VN1/VN2) in this preparation (1). In the present study, the known competitive vanilloid antagonist capsazepine inhibited the above capsaicin-mediated effects in a manner that was indicative of binding at specific vanilloid recognition sites. Low concentrations of capsazepine selectively inhibited the increased VO2 produced by the putative VN1 receptor at submicromolar concentrations of capsaicin, while the inhibition of VO2 produced by high concentrations of capsaicin (putative VN2) was enhanced. These observations, showing different susceptibilities to blockade by capsazepine, further support the presence of two vanilloid receptor subtypes in the rat hindlimb. Schild plots of the data yielded variable slopes that approach unity at greater responses to capsaicin (mean KB = 8.44 +/- 2.08 microM and 7.28 +/- 0.78 microM for VO2 and perfusion pressure curves, respectively). Low concentrations of the capsaicin antagonist ruthenium red selectively blocked the putative VN2 receptor-mediated effects produced by high concentrations of capsaicin. The noncompetitive nature of this inhibitor suggests an operation through separate receptor-coupled ion channel complexes at high and low concentrations of the vanilloid. Tetrodotoxin failed to attenuate any changes produced by capsaicin, suggesting that the mechanism of action of capsaicin in the rat hindlimb may differ from other tissues.

Animals↗
PubMed1995

Capsaicin pretreatment attenuates chronic hypoxic pulmonary hypertension.

Capsaicin pretreatment was used to deplete tachykinins in order to study the role of tachykinins in chronic hypoxia-induced pulmonary hypertension. Forty three young Wistar rats weighing 235 +/- 4 g were randomly divided into four groups: control (n = 10); capsaicin pretreatment (n = 10); intermittent chronic hypoxia (n = 10); and capsaicin pretreatment + intermittent chronic hypoxia (n = 13). Control animals breathed room air. Rats in the capsaicin pretreatment groups were given capsaicin via subcutaneous injection over a three-day period. Hypobaric hypoxia was intermittently applied by placing animals into a hypobaric chamber with a barometric pressure of 380 Torr for two weeks. In the capsaicin pretreatment + intermittent chronic hypoxia group, rats were exposed to intermittent hypoxia for two weeks immediately after the last dose of capsaicin. Subsequently, pulmonary vascular function, as well as substance P (a tachykinin) level and neutral endopeptidase (NEP, the major degradation enzyme for tachykinins) activity in the lungs were measured. Chronic hypoxia caused significant increases in pulmonary artery pressure, right ventricle/(left ventricle + septum) weight ratio, hematocrit, and lung substance P level, as well as a significant decrease in lung NEP activity. All these chronic hypoxia-induced changes were significantly lessened by capsaicin pretreatment. Capsaicin pretreatment alone did not induce any significant alteration in vascular function. These results suggest that the chronic hypoxia causes an increase in lung tachykinin levels which, in turn, enhance the development of pulmonary hypertension.

Animals↗
PubMed1994

The human nasal response to capsaicin.

Airway sensory nerves play a role in reactions to inhaled allergens, irritants, and physical stimuli. Capsaicin, the pungent principle of hot peppers, stimulates a subcategory of sensory nerves. To study the consequences of selective activation of airway sensory nerves in the human nose, we administered capsaicin nasal challenges to eight volunteers (four normal subjects and four subjects with perennial allergic rhinitis). Capsaicin (20 mumol/L), when sprayed into the nose, induced burning, rhinorrhea, and lacrimation. Capsaicin also induced a significant increase in total protein content of nasal lavage fluid after challenge compared with vehicle (increase from before challenge to 1 minute after challenge, 172 +/- 55 vs 46 +/- 29 micrograms/ml, p < 0.001). In contrast to many animal studies, capsaicin did not increase vascular permeability in the airway, because albumin content of nasal lavage fluid was not increased (p = 0.86). On the other hand, lactoferrin, a marker of glandular secretion, was increased (p < 0.005). Repetitive capsaicin challenge every 10 minutes led to tachyphylaxis of symptoms, total protein secretion, and lactoferrin secretion. Compared with vehicle, unilateral capsaicin (6 mmol/L) disk challenge induced significant secretion both ipsilateral (21.3 +/- 4.2 vs 4.9 +/- 2.1 mg, p < 0.01) and contralateral (18.2 +/- 4.4 vs 7.4 +/- 1.9 mg, p < 0.04) to challenge. Thus we have shown that capsaicin challenge to the human nose leads to airway sensory nerve activation. Further, we have demonstrated that capsaicin stimulates a predominantly central neuronal response and that the induced secretory response is of glandular rather than vascular origin.

Adult↗