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PubMed1990

Actions of capsaicin on peripheral nociceptors of the neonatal rat spinal cord-tail in vitro: dependence of extracellular ions and independence of second messengers.

1. We have tested the hypothesis that capsaicin-induced activation, desensitization and impairment of peripheral nociceptor function is mediated by separate mechanisms. This was investigated by use of an in vitro preparation of the neonatal rat spinal cord with the functionally attached tail in which the cord and tail were separately superfused with physiological solution. Activation of peripheral fibres by noxious (capsaicin, bradykinin, 5-hydroxytrptamine, heat, pinch) and innocuous (light brush) stimuli was assessed by recording the depolarization of a spinal ventral root (L3-L5). 2. Brief administration of capsaicin produced dose-related depolarizing responses (EC50 = 280 nM). These responses could be reproduced for many hours following the repeated application of capsaicin at a submaximal concentration. Prolonged application of 0.5-2.0 microM capsaicin induced a selective desensitization to subsequent brief administrations of capsaicin. Prolonged administration at 20-50 microM produced an additional non-selective reduction in responses to all noxious stimuli without changing innocuous brush responses. 3. Removal of extracellular calcium from the tail superfusate did not reduce the response to capsaicin or prevent capsaicin-induced desensitization. However, high concentrations of capsaicin no longer induced a non-specific reduction of responses to other noxious stimuli. The response to a brief administration of capsaicin was unaffected by calcium channel blocking drugs including nifedipine, cadmium or omega-conotoxin. On the other hand high extracellular calcium increased the incidence of the non-selective reduction of responses to all noxious stimuli produced by high concentrations of capsaicin. 4. Replacement of extracellular sodium with choline blocked peripheral nerve conduction but did not prevent the desensitization produced by capsaicin. In addition, high concentrations of capsaicin were less effective in reducing the responsiveness to other noxious stimuli. 5. Neither capsaicin-evoked responses nor capsaicin-induced desensitization were affected by the administration of forskolin, dibutyryl cyclic AMP, nitroprusside, dibutyryl cyclic GMP, beta-12,13 phorbol dibutyrate, trifluoperazine, indomethacin, staurosporine or mepacrine, in the tail superfusate. 6. These data suggest that capsaicin-induced activation, desensitization and impairment of peripheral nociceptors may be separable phenomena. Extracellular calcium is not required for capsaicin-induced activation or desensitization but calcium as well as sodium are important for capsaicin-induced impairment of nociceptive responses. Desensitization may occur independently of peripheral fibre activation and cannot be attributed to a central mechanism. Finally neither capsaicin-induced activation nor desensitization require the participation of a second messenger.

Animals↗
PubMed2000

Lack of integrative control of body temperature after capsaicin administration.

BACKGROUND: Body temperature is usually regulated by opposing controls of heat production and heat loss. However, systemic administration of capsaicin, the pungent ingredient of hot peppers, facilitated heat production and heat loss simultaneously in rats. We recently found that the capsaicin-induced heat loss and heat production occur simultaneously and that the biphasic change in body temperature is a sum of transient heat loss and long-lasting heat production. Moreover, suppression of the heat loss response did not affect capsaicin-induced heat production and suppression of heat production did not affect capsaicin-induced heat loss. These observations suggest the independent peripheral mechanisms of capsaicin-induced thermal responses. Thus, the capsaicin-induced thermal responses apparently lack an integrated control. METHODS: Male Wistar rats were maintained at an ambient temperature of 24 +/- 1 degrees C on a 12 h on-off lighting schedule at least for two weeks before the experiments. They were anesthetized with urethane (1.5 g/kg, i.p.) and placed on a heating pad, which was kept between 29 and 30 degrees C. Skin temperature(Ts) was measured with a small thermistor, which was taped to the dorsal surface of the rat's tail, to assess vasoactive changes indirectly. Colonic temperature(Tc) was measured with another thermistor inserted about 60 mm into the anus. O2 consumption was measured by the open-circuit method, and values were corrected for metabolic body size (kg0.75). Capsaicin (Sigma) was dissolved in a solution comprising 80% saline, 10% Tween 80, and 10% ethanol, and injected subcutaneously at a dose of 5 mg/kg. Each rat received a single injection of capsaicin because repeated administration of capsaicin renders an animal insensitive to the subsequent administration of capsaicin. Laminectomy was performed at the level of the first and second cervical vertebrae to expose the cervical spinal cord for sectioning. The brain was transected at 4-mm rostral from the interaural line with an L-shaped knife. RESULTS: After administration of capsaicin, O2 consumption increased from 13.5 +/- 0.4 mL/min/kg0.75 at 0 min to a peak of 15.9 +/- 0.4 mL/min/kg0.75 at 71 min and gradually declined but remained higher than the basal value until the end of the 4-h observation period. Ts also immediately increased from 27.7 +/- 0.2 degrees C to 31.9 +/- 0.3 degrees C at 39 min, and it returned to the baseline level within 90 min after the capsaicin administration. Tc initially decreased from 37.1 +/- 0.1 degrees C to 36.8 +/- 0.2 degrees C at 43 min and then gradually increased over the baseline level and remained at 37.6 +/- 0.2 degrees C until the end of the experiment. In spinalized rats, the capsaicin-induced increases in O2 consumption was largely attenuated, while the basal O2 consumption was similar to that of control rats. The basal Ts of spinalized rats was 32.4 +/- 0.3 degrees C, which was higher than that of control rats. Capsaicin increased Ts by less than 1 degree C, and Tc did not change after the capsaicin administration. O2 consumption of decerebrated rats was statistically higher than that of control rats after the injection of capsaicin. However, capsaicin did not increase Ts, showing a lack of a vasodilatory response. Decerebration between the hypothalamus and midbrain prevented the capsaicin-induced heat loss but not the heat production response. CONCLUSION: These results show that the capsaicin-induced heat production and heat loss are controlled separately by the brainstem and by the forebrain, respectively, and suggest that the body temperature regulation is performed without an integrative center.

Animals↗
PubMed2004

Chemical nociception in the jejunum induced by capsaicin.

BACKGROUND AND AIMS: Chemonociception in the human small intestine has not been studied extensively. Although capsaicin can cause intestinal sensations, it is not known if this is due to stimulation of chemoreceptors or to motor changes. Our aims were to evaluate motor activity during capsaicin induced nociception and to compare qualities of jejunal nociception induced by capsaicin and mechanical distension. METHODS: Twenty nine healthy subjects swallowed a tube with a perfusion site at the ligament of Treitz and, 7 cm distally, a barostat balloon. Phasic motor activity was measured around the perfusion site and the balloon. Capsaicin solutions (40, 200, and 400 microg/ml) 2.5 ml/min were perfused for 60 minutes or until severe discomfort occurred. A graded questionnaire for seven different sensations was completed every 10 minutes and after capsaicin perfusion was replaced by saline perfusion because of severe discomfort. Sensations arising from pressure controlled distensions were assessed before and after capsaicin perfusion when sensations had stopped (n = 19), or during capsaicin administration when no discomfort was reported (n = 5). RESULTS: Capsaicin perfusion induced feelings of pressure, cramps, pain, and warmth. The quality and abdominal location of these sensations were similar to those induced by distension, except for warmth (p<0.01) and pressure (p<0.05). Seven of 12 subjects receiving 40 microg/ml capsaicin and all subjects receiving higher capsaicin concentrations developed discomfort. Perfusion had to be stopped after 55 (3.3), 15 (5.7), and 10 (2.2) minutes with 40, 200, and 400 microg/ml capsaicin, respectively, whereafter the sensations disappeared within 10 minutes. Repeated capsaicin (200 microg/ml) applications significantly reduced the time until discomfort occurred (p = 0.01). Jejunal tone was not altered by capsaicin but phasic activity proximal to the perfusion site was reduced during capsaicin induced discomfort (p<0.001). Pain thresholds during distensions were not different before and after capsaicin perfusion. CONCLUSION: Despite the similarities in abdominal localisation and perceptional quality of capsaicin and distension induced sensations, our results rule out the fact that abdominal discomfort evoked by capsaicin involves sensitisation of mechanoreceptors or an increase in phasic and tonic motor activity. Capsaicin evokes abdominal sensations by stimulation of chemoreceptors which proves the existence of chemonociception in the human small intestine.

Abdomen↗
PubMedDate not supplied

Role of capsaicin-sensitive sensory nerves in gastroprotection against acid-independent and acid-dependent ulcerogens.

Treatment with small doses of topical capsaicin protects the gastric mucosa from the damage by strong irritants but functional ablation of sensory nerves by pretreatment with larger dose of parenteral capsaicin augments the formation of gastric lesions via unknown mechanism. This study was designed to determine the role of gastric acid secretion, mucosal blood flow (GBF) and prostaglandins (PG) generation in the gastroprotection induced by small doses of topical or parenteral capsaicin in rats with intact or capsaicin-deactivated sensory nerves. Gastric lesions were produced in rats with intact sensory nerves (series A) or capsaicin-deactivated nerves (series B) using intragastric (i.g.) application of 100% ethanol, acidified aspirin (ASA) or water immersion and restraint stress (WRS). Pretreatment with i.g. capsaicin (0.12-1.0 mg/kg) in rats with intact sensory nerves (series A) reduced dose-dependently the mucosal damage caused by ethanol, ASA or WRS, the dose inhibiting the lesion area by 50% (ID50) being 0.3, 0.5 and 0.7 mg/kg, respectively. This protection was accompanied by a significant rise in gastric mucosal blood flow (GBF). Parenteral application of capsaicin (1.2-10 mg/kg s.c.) that in intact rats dose-dependently increased GBF, also dose-dependently reduced gastric damage induced by ASA or WRS (but not by ethanol), the ID50 being 5 and 3 mg/kg, respectively. The reduction by i.g. capsaicin of ethanol-or WRS-induced mucosal lesions was accompanied by a rise in GBF and this effect was reversed by indomethacin at a dose that suppressed endogenous PG biosynthesis by about 90%, indicating that PG are involved in the protective activities of topical capsaicin. Furthermore, topical and to a lesser extent parenteral capsaicin given to rats with intact or deactivated sensory nerves inhibited gastric acid and pepsin outputs, suggesting that this inhibition could contribute to the capsaicin-induced gastroprotection against acid-dependent mucosal lesions (ASA or WRS). Capsaicin deactivation of sensory nerves aggravated mucosal lesions induced by all three ulcerogens and this effects was accompanied by a marked decrease in GBF. In such capsaicin-deactivated rats, topical capsaicin also reduced ethanol-, ASA- or WRS-induced lesions, while parenteral capsaicin was effective only in the protection against the damage induced by acidified ASA and WRS but not by ethanol. The protection against WRS lesions and accompanying rise in GBF by parenteral capsaicin were also reversed by the pretreatment with indomethacin applied in a dose suppressing the generation of PG. We conclude that capsaicin is capable of protecting gastric mucosa in rats with both intact and capsaicin-deactivated rats and that this protective activity depends, at least in part, upon its hyperemic and antisecretory effects that may be mediated, at least in part, by endogenous release of PG.

Animals↗
PubMed1999

Capsaicin inhibits phospholipase C-mediated Ca(2+) increase by blocking thapsigargin-sensitive store-operated Ca(2+) entry in PC12 cells.

Capsaicin has been shown to act through vanilloid receptors, which are temperature-sensitive cation channels. However, there also are indications that suggest the capsaicin effect is not mediated by the vanilloid receptor. We therefore investigated the effect of capsaicin on the phospholipase C-mediated Ca(2+) rise in PC12 cells. Capsaicin caused a rapid decline in extracellular ATP- or bradykinin-induced calcium transients to the basal level without significant attenuation of the peak level. However, capsaicin did not inhibit either ATP- or bradykinin-induced Ca(2+) elevation in the absence of extracellular Ca(2+) or inositol-1,4,5-trisphosphate production. Capsaicin also inhibited ATP-induced norepinephrine secretion. Capsaicin dramatically reduced the thapsigargin-induced sustained Ca(2+) level, suggesting that capsaicin inhibits thapsigargin-sensitive store-operated Ca(2+) entry (SOCE). Thapsigargin-induced Ba(2+) and Mn(2+) influx was also inhibited by capsaicin. Furthermore, capsaicin overlapped SK&F96365 in inhibiting thapsigargin-sensitive SOCE. Capsaicin-induced inhibition of SOCE also occurred in thapsigargin-treated Jurkat-T cells, which have a rather prominent SOCE. Resiniferatoxin, a vanilloid receptor agonist, did not mimic the effect of capsaicin. Ruthenium red and capsazepine, which are known to inhibit the vanilloid receptor, did not affect this capsaicin effect. The results suggest that capsaicin does not mediate vanilloid receptor signaling when inhibiting the thapsigargin-sensitive SOCE. The capsaicin action was also not mediated by activation of protein kinase C because phorbol-12-myristate 13-acetate and capsaicin did not overlap each other's effect and GF109203X did not reverse the inhibitory effect of capsaicin. The results suggest that capsaicin negatively modulates thapsigargin-sensitive SOCE subsequent to phospholipase C activation.

Animals↗
PubMed1988

Capsaicin challenge, reflex bronchoconstriction, and local action of substance P.

Capsaicin was administered as an aerosol to unanesthetized guinea pigs in a whole body plethysmograph and intravenously to anesthetized guinea pigs to investigate its mechanism of action. Capsaicin increased specific airway resistance in the unanesthetized guinea pigs and increased insufflation pressure in anesthetized guinea pigs. To investigate the possible reflex action of capsaicin, an atropine or lidocaine aerosol was administered before the capsaicin aerosol challenge in unanesthetized guinea pigs. Both lidocaine and atropine reduced the effect of capsaicin. However, neither intravenous atropine nor bilateral vagotomy antagonized the effect of injected capsaicin in the anesthetized guinea pigs. To investigate further the possible action of capsaicin, spantide (a substance P receptor antagonist) was administered before capsaicin challenge. Spantide injection in anesthetized guinea pigs attenuated the effects of the intravenous capsaicin challenge. In unanesthetized guinea pigs spantide pretreatment, as an aerosol, did not ameliorate the effects of a capsaicin aerosol challenge. However, intraperitoneal administration of spantide did reduce the effect of the capsaicin aerosol challenge as the specific airway resistance increased. Therefore, capsaicin produced its effects independent of vagal reflexes, although reflex actions of capsaicin could have occurred through other pathways. Reflex actions of capsaicin, however, were demonstrable only in the unanesthetized guinea pig. Because spantide attenuated the effect of capsaicin, increased insufflation pressure and specific airway resistance due to capsaicin challenge in both unanesthetized and anesthetized guinea pigs may be attributed, at least in part, to capsaicin's induction of substance P release or the release of other tachykinins.

Aerosols↗
PubMed1998

Chronotropic, inotropic and lusitropic effects of capsaicin on isolated rat atria.

This work includes results on chronotropic, inotropic and lusitropic changes induced by capsaicin on isolated rat atria. As regards spontaneous frequency, it was stimulated from 10(-9) M up to 7 x 10(-7) M of capsaicin. A simultaneous depression in developed force (F) showed a significant correlation with this positive chronotropic effect up to 7 x 10(-8) M of capsaicin, which is the result of the negative staircase phenomenon in the rat heart. The correlation was lost at 2 and 7 x 10(-7) M of capsaicin since in spite of the sustained increase in atrial rate the decrease in F was reversed and then depressed again at 2 and 7 x 10(-6) M of capsaicin without changes in frequency. A concentration of capsaicin that overcome the negative staircase phenomenon, 5 x 10(-7) M, was tested as unique dose resulting in stimulation of the chronotropic, inotropic and lusitropic states of the atria. Percentual differences with respect to control values were maximal after 1-3 minutes for frequency (10 +/- 3%), F (29 +/- 4%), maximal velocity of force development (+F = 50 +/- 12%) (in all cases +F and -F bold indicates +F and -F, respectively), and maximal velocity of relaxation (-F = 64 +/- 13%); a positive lusitropic effect was significant after 8-10 minutes (+F/-F = 17 +/- 7%). Capsaicin did not affect the rat atria in the presence of 10(-6) M of ruthenium red, a blocker of capsaicin activation of sensory nerves, indicating that the stimulatory effects were entirely mediated by the release of neurotransmitters and that this concentration of capsaicin was not deleterous "per se". Capsaicin elicited similar inotropic responses in electrically driven isolated atria (+F = 41 +/- 9%) but the positive lusitropic effect was lost suggesting that capsaicin-induced increases in -F are limited at a frequency higher than the spontaneous frequency (11 +/- 6 vs. 32 +/- 4%, respectively). 10(-6) M of CGRP8-37, an antagonist of CGRP1 receptors, suppress the stimulatory effects of capsaicin on atrial contraction. In summary, atrial rate as compared to atrial contraction is more sensitive to the neurotransmitter released by capsaicin, which results in mechanical effects expressing the negative staircase phenomenon in the rat at low concentrations of capsaicin. The positive chronotropic, inotropic and lusitropic responses elicited by capsaicin are mediated by the release of neurotransmitters from sensory fibbers and no deletereous effects of capsaicin "per se" became evident when the release of neuropeptides was prevented. Atrial contraction was depressed at higher capsaicin concentrations than the one showing stimulatory effects. Stimulation of atrial contractility is mediated by activation of CGRP receptors.

Animals↗
PubMed1984

Local and systemic capsaicin pretreatment inhibits sneezing and the increase in nasal vascular permeability induced by certain chemical irritants.

The effects of local exposure to chemical irritants and mechanical stimulation on sneezing reflexes have been studied in normal and capsaicin-pretreated, conscious guinea-pigs. The influence of local and systemic capsaicin pretreatment on vascular permeability to plasma proteins and the cardiovascular effects of local application of capsaicin to the nasal mucosa have also been studied in anaesthetized animals. Local application of capsaicin (threshold dose 3 microM), nicotine (threshold dose 300 microM) or formalin to the nasal mucosa induced reflex sneezing discharges. Systemic or local capsaicin pretreatment abolished or reduced the sneezing responses to capsaicin and formalin. The response to nicotine was also reduced following local pretreatment with capsaicin, while the response to systemic pretreatment with capsaicin was only slightly affected. The sneezing response to mechanical stimulation was not affected by capsaicin pretreatment. Pretreatment with a local anaesthetic induced a similar dose-dependent inhibition of the sneezing responses to both capsaicin and nicotine. Local application of disodium cromoglycate to the nasal mucosa reduced the sneezing response to capsaicin, but not that to nicotine. Local pretreatment with the 3 mM and 30 mM capsaicin solution inhibited the increase in vascular permeability to plasma proteins in the nasal mucosa induced by i.v. capsaicin. Local pretreatment with capsaicin did not result in any reduction in the capsaicin-induced permeability in the ureter, suggesting that such treatment did not have any major systemic toxic effects. However, a small, acute increase in respiratory insufflation pressure, indicating broncho constriction, was seen when the 30 mM capsaicin solution was applied to the nasal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1999

Involvement of endogenous tachykinins and CGRP in the motor responses produced by capsaicin in the guinea-pig common bile duct.

In functional experiments, we have investigated the effect exerted by neurotransmitters released from capsaicin-sensitive primary afferent nerve terminals in the isolated guinea-pig common bile duct. In resting preparations, capsaicin (0.1 microM) produced a quick contraction (45.1+/-4% of KCl 80mM) which was abolished by either atropine (1 microM) or tetrodotoxin (0.5 microM). The tachykinin receptor-selective antagonists GR 82334 (NK1 receptor-selective; 3 microM), MEN 11420 (NK2 receptor-selective; 1 microM) and SR 142801 (NK3 receptor-selective; 0.1 microM) administered separately failed to reduce the capsaicin-evoked contraction, whereas any combination of the three antagonists was effective: GR 82334 plus MEN 11420, 36+/-7% reduction; GR 82334 plus SR 142801, 48+/-4% reduction; MEN 11420 plus SR 142801, 55+/-3% reduction; GR 82334 plus MEN 11420 plus SR 142801, 57+/-5% reduction. Neither the CGRP1 receptor antagonist h-CGRP (8-37) (1.5 microM) nor the P2X purinoceptor antagonist PPADS (50 microM) affected the contractile response to capsaicin. The effect of capsaicin (0.1 microM) was abolished by pretreatment with capsaicin itself (10 microM for 15 min). Human calcitonin gene-related peptide (h-CGRP; 0.1 microM) mimicked the effect of capsaicin on resting preparations (contractile response =28% of KCl 80 mM). In preparations precontracted with a submaximal concentration of KCl (24 mM), and in the presence of atropine (1 microM), GR 82334 (3 microM) and MEN 11420 (3 microM), capsaicin (1 microM) produced a tetrodotoxin-insensitive long-lasting relaxation (45+/-3% reduction of tone, at 4min from administration), which was unaffected by the nitric oxide (NO) synthase inhibitor, L-NOARG (100 microM). h-CGRP (10-50 nM) produced a similar sustained relaxation of precontracted preparations (59+/-4% reduction of tone). h-CGRP (8-37) (1.5 microM) almost completely reversed the relaxations produced by both capsaicin and h-CGRP. Application of electrical field stimulation (EFS: trains of stimuli of 10Hz; 0.25ms pulse width; supramaximal voltage; for 60s) to precontracted preparations produced a sustained, tetrodotoxin (1 microM)-sensitive relaxation (32+/-4% reduction of tone). L-NOARG (100 microM) greatly reduced (69+/-5% inhibition) the EFS-elicited relaxation. A complete reversal of the relaxant response to EFS into a contraction was obtained by administering L-NOARG to preparations in which a functional blockade of capsaicin-sensitive primary afferent neurons had been achieved by incubating the tissue with capsaicin (10 microM) for 15 min. At immunohistochemistry, tachykinin- and CGRP-immunoreactivities (TK-IR/CGRP-IR) were detected in varicose nerve fibers throughout the common bile duct, while TK-IR cell bodies were observed in the terminal portion (ampulla) only. In vivo pretreatment with capsaicin (50 mg/kg; 6-7 days before) decreased the number of CGRP-IR nerves, whereas the TK-IR neural network was apparently unchanged. In conclusion, our data provide functional evidence for the presence of capsaicin-sensitive primary afferent nerve endings in the guinea-pig terminal biliary tract, whose stimulation by capsaicin or EFS produces the release of tachykinins and CGRP. In addition, morphological evidence is provided that the bulk of TK-IR material in the biliary tract is contained in intrinsic neuronal elements, while CGRP in this tissue is of extrinsic origin only. Tachykinins, probably released in small amounts by capsaicin, act by activating receptors of the NK1, NK2 and NK3 type, most probably located on intrinsic cholinergic neurons, which in turn release ACh to produce the final excitatory motor response. The contractile response to capsaicin obtained in the presence of the three tachykinin receptor antagonists could be due to the co-released CGRP and/or to other unknown neurotransmitters. CGRP produces either indirect excitatory or direct inhibitory responses by stimulation of CGRP2 and CGRP1 receptors, respectively.

Animals↗
PubMed1984

Neurophysiological effects of capsaicin.

Data obtained from neonatally treated rats are fairly consistent. However, there is disagreement as to whether mechanical and thermal nociceptive thresholds are elevated or unchanged in this group. There are at least two major areas of disagreement in adult animal capsaicin research. Behavioral data are extremely variable. The thermal nociceptive threshold after systemic capsaicin has been reported to be both raised and lowered. After intrathecal capsaicin injection, the thermal nociceptive threshold was reported raised, but onset and duration of responses varied and some animals exhibited no changes. Capsaicin application to peripheral nerve, however, drastically increased thermal threshold. Mechanical pain threshold has been reported both increased and unchanged after systemic capsaicin treatment and unchanged after intrathecal injection. Obviously, capsaicin's effects upon pain perception are not fully understood. Although lower on the phylogenetic scale than many mammals, rodents exhibit complex individualistic behavior. Lower vertebrates may eventually provide more simple behavioral models for pain tolerance. Investigators also disagree as to whether C fibres can conduct action potentials after local capsaicin application. C fibre conduction was reported unaffected by capsaicin in an acute preparation and for 13-21 days after treatment. On the other hand, C fibre compound action potentials have been reported diminished for up to 2 h after capsaicin application. Additional conduction impairment studies will be useful in comparing peripheral and intrathecal capsaicin application. There is general agreement that, allowing for variation in dosages and route of administration, capsaicin causes central and peripheral C fibre damage, though never as extensive in adults as in neonates. Neonatal capsaicin treatment (always s.c.) results in destruction of C and some A delta fibres and their central terminals. Capsaicin causes degeneration of C terminals in the adult CNS only when applied centrally. In both neonates and adults, s.c. capsaicin depletes the putative 'pain' peptide neurotransmitter, SP, from peripheral and sensory neurons and the tissues they innervate but not from the gut. Capsaicin-induced SP depletion in neonates is permanent. Systemic administration to adult depleted SP from much the same areas as observed in neonates, but all areas but the medulla exhibited a slow, regional recovery. Intraventricular injection of capsaicin depleted SP in the adult medulla only, while other SP-containing areas affected by systemic injection remained intact.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1997

Acute and neonatal capsaicin treatment inhibit jejunal amino acid absorption through a Na+-dependent mechanism.

It has recently been shown that capsaicin inhibits alanine absorption in rat jejunum via mechanisms that involve intestinal capsaicin-sensitive primary afferent (CSPA) fibers. This study provides further evidence that the effect of capsaicin is neurally mediated and demonstrates that CSPA fibers regulate Na+-dependent amino acid absorption. In vivo, basal alanine absorption in rats neonatally treated with capsaicin was reduced by 35% below control. Furthermore, intraluminal perfusion of 400 microM capsaicin reduced jejunal alanine absorption by 31% in sham rats but had no significant effect in rats neonatally treated with capsaicin. In vitro, capsaicin significantly reduced uptake of alanine and proline by jejunal strips but had no effect on uptake of lysine. Tetrodotoxin (0.2 microM) partially blocked the effects of capsaicin but did not itself affect alanine absorption. Capsaicin reduced unidirectional mucosal-to-serosal alanine (1 mM) influx by 33%, an effect that becomes significant after 5 min of preincubation with capsaicin. Neonatal capsaicin treatment reduced basal alanine influx in jejunal strips by 37%; however, preincubation of these strips with capsaicin had no significant effect. Kinetic analysis of alanine steady-state uptake and influx by jejunal strips incubated with capsaicin revealed that capsaicin reduced the Na+-dependent component of alanine influx into intestinal epithelial cells. Long-term sensory denervation by capsaicin also decreased the Na+-dependent component of alanine absorption. These data suggest that intestinal capsaicin-sensitive primary afferent fibers regulate Na+-dependent amino acid absorption.

Alanine↗
PubMed2006

[Preparation and in vitro and in vivo evaluations of topically applied capsaicin transfersomes].

AIM: To prepare capsaicin transfersomes and evaluate them in vitro and in vivo. METHODS: Capsaicin transfersomes were prepared by high shear dispersing machine and evaluated by entrapment efficiency, release rate, in vitro skin permeation and distribution in different tissues in vivo. RESULTS: Capsaicin transfersomes were composed of single unilamellar vesicles with an average diameter of 150.6 nm. Capsaicin entrapment efficiency increased distinctly with increasing of concentration of lecithin and entrapment efficiency is 96.7% while concentration of lecithin to 8%. Cumulative release amount of capsaicin is in direct proportion to the ethanol concentration in the receptor medium. In vitro capsaicin cumulative penetration amount showed higher levels in transfersomes than cream and suspension in rat abdominal skin. Abdominal skin cumulative penetration amount in vitro of capsaicin transfersomes in mouse was significantly higher than that from rat and men. In the same way, abdominal skin epidermal membrane cumulative penetration amount in vitro of capsaicin transfersomes was significantly higher than that from derma and full skin in human abdominal skin. The capsaicin tissue distribution of capsaicin injection by multiple celiac injections in rats is different: bone > plasma > skin > muscle. There is a similar result by multiple thigh topical application of capsaicin transfersomes: bone > skin > plasma > muscle. CONCLUSION: Entrapment efficiency of capsaicin transfersomes reached the criterion of China Pharmacopoeia (> 80%) and capsaicin skin penetration can be increased by capsaicin transfersomes. It should be noted that the diverse characters and levels of skin may probably affect the permeating capability of capsaicin. Capsaicin tissue distribution in bone and muscle is similar and is different in plasma and skin by multiple injections and topical skin apply.

Administration, Cutaneous↗
PubMed1988

Capsaicin-induced ion fluxes in dorsal root ganglion cells in culture.

Capsaicin is a pungent pain-producing compound found in plants of the capsicum family; it exerts excitatory, desensitizing, and toxic effects on a subset of sensory neurons, including the polymodal nociceptor population. We have carried out a quantitative study of capsaicin-induced fluxes of sodium, guanidine, calcium, rubidium, and chloride ions in cultures of neonatal and adult rat DRG neurons, in conjunction with the use of a histochemical stain that identifies capsaicin-sensitive neurons by means of cobalt uptake. Those cells that take up cobalt in a capsaicin-dependent manner (EC50 = 0.2 microM) represent about 50% of the total neuronal population derived from neonatal DRGs on short-term culture. Overnight treatment of cultures with 2 microM capsaicin leads to the loss of the cobalt-staining subpopulation. The capsaicin-insensitive neurons contain immunoreactive neurofilament epitopes that are present in fewer than 10% of capsaicin-sensitive neurons. This observation provides indirect evidence that the sensitive cells correspond to the small, dark B-type neurons, which are negative for neurofilament immunoreactivity in vivo. A capsaicin-dependent calcium uptake (EC50 = 0.2 microM), as measured by 45Ca incorporation, is shown by a DRG neuronal subpopulation that, like the cobalt-staining population of DRG neurons, is lost after overnight capsaicin treatment (2 microM). Capsaicin application leads to the accumulation of millimolar levels of calcium within a few minutes. Cadmium and other divalent cations block capsaicin-induced calcium uptake, but little or no inhibition is seen with organic calcium channel antagonists. Mitochondria, rather than the endoplasmic reticulum, are the probable destination of the internalized calcium, because ruthenium red inhibits calcium uptake (IC50 = 0.05 microM), whereas methylxanthines are inactive. The subset of sensory neurons that takes up calcium also releases 86Rb when exposed to capsaicin (EC50 = 0.06 microM). No efflux of 36Cl ions could be induced by capsaicin. These cells also show a capsaicin-induced uptake of 22Na or 14C guanidine (EC50 = 0.06 microM). In contrast, chick DRG cells in culture showed no capsaicin-induced calcium or cobalt uptake. Primary cultures of rat superior cervical ganglion neurons and Schwann cells, and a number of neuronal cell lines, also failed to respond to capsaicin, as judged by the calcium, cobalt, or guanidine uptake assays.

Animals↗