Distribution and function of the cannabinoid-1 receptor in the modulation of ion transport in the guinea pig ileum: relationship to capsaicin-sensitive nerves

We investigated the distribution and function of cannabinoid (CB)(1) receptors in the submucosal plexus of the guinea pig ileum. CB(1) receptors were found on both types of submucosal secretomotor neurons, colocalizing with VIP and neuropeptide Y (NPY), the noncholinergic and cholinergic secretomotor neurons, respectively. CB(1) receptors colocalized with transient receptor potential vanilloid-1 receptors on paravascular nerves and fibers in the submucosal plexus. In the submucosal ganglia, these nerves were preferentially localized at the periphery of the ganglia. In denervated ileal segments, CB(1) receptor immunoreactivity in submucosal neurons was not modified, but paravascular and intraganglionic fiber staining was absent. Short-circuit current (I(sc)) was measured as an indicator of net electrogenic ion transport in Ussing chambers. In the ion-transport studies, I(sc) responses to capsaicin, which activates extrinsic primary afferents, and to electrical field stimulation (EFS) were reduced by pretreatment with the muscarinic antagonist atropine, abolished by tetrodotoxin, but were unaffected by VIP receptor desensitization, hexamethonium, alpha-amino-3-hydroxy-5-methlisoxazole-4-proprionic acid, or N-methyl-d-aspartate glutamate receptor antagonists. The responses to capsaicin and EFS were reduced by 47 +/- 12 and 30 +/- 14%, respectively, by the CB(1) receptor agonist WIN 55,212-2. This inhibitory effect was blocked by the CB(1) receptor antagonist, SR 141716A. I(sc) responses to forskolin or carbachol, which act directly on the epithelium, were not affected by WIN 55,212-2. The inhibitory effect of WIN 55,212-2 on EFS-evoked secretion was not observed in extrinsically denervated segments of ileum. Taken together, these data show cannabinoids act at CB(1) receptors on extrinsic primary afferent nerves, inhibiting the release of transmitters that act on cholinergic secretomotor pathways.     

TNBS ileitis evokes hyperexcitability and changes in ionic membrane properties of nociceptive DRG neurons

This study examines whether intestinal inflammation leads to changes in the properties of ion channels in dorsal root ganglia (DRG) neurons. Ileitis was induced by injection of trinitrobenzene sulfonic acid (TNBS), and DRG neurons innervating the ileum were labeled using fast blue. Intracellular recording techniques were used to measure electrophysiological properties of acutely dissociated neurons 12-24 h after dissection. Nociceptive neurons were identified by sensitivity to capsaicin, tetrodotoxin resistance, and size (<30 microm). The action potential threshold in neurons from TNBS-treated animals was reduced by >70% compared with controls (P < 0.001), but the resting membrane potential was unchanged. Cell diameter, input resistance (67%), and action potential upstroke velocity (22%) increased in the TNBS group (P < 0.05). The number of action potentials discharged increased in the TNBS group (P < 0.001), whereas application of 4-aminopyridine to control cells mimicked this effect. This study demonstrates that ileitis induces hyperexcitability in nociceptive DRG neurons and changes in the properties of Na(+) and K(+) channels at the soma, which persist after removal from the inflamed environment.     

Alternative changes of activity of alpha2-macroglobulin and alpha1-antitrypsin in rat blood following damage in capsaicin-sensitive nerves

Effects of functional ablation of peptidergic sensory nerves with neurotoxic doses of capsaicin (150 mg/kg, s/c) as well as of their stimulation with small doses of capsaicin (5 mg/kg, i/p) on activity of proteinase inhibitors: alpha1-antitrypsin (alpha1-AT)-serine proteinase inhibitor and alpha2-macroglobulin (alpha2-MG)-nonspecific inhibitor were investigated in rat blood. The present results indicate alternative changes in activity of these proteinase inhibitors after damage of capsaicin-sensitive nerves: increasing decline in activity of alpha1-AT 1 and 3 or 14 days after administration of capsaicin and increase in activity of alpha2-MG land 3 day after the injection. The stimulation of afferent nerves with capsaicin did not change activity of the proteinase inhibitors 1 and 24 hours after the injection. It is suggested that the stable decrease in activity of alpha1-AT during a long period after the damage of capsaicin-sensitive nerves indicates an important role for these nerves in the regulating alpha1-AT that may exert a tonic effect on the activity alpha1-AT.     

An increase in the synthesis and release of calcitonin gene-related peptide in two-kidney,one-clip hypertensive rats

Previous investigations have indicated that capsaicin-sensitive sensory nerves play an important role in modulation of the peripheral resistance of the circulation system. In the present study, we examined the role of capsaicin-sensitive sensory nerves in two-kidney, one-clip (2K1C) renovascular hypertension rats. Systolic blood pressure (BP) was monitored by the tail-cuff method throughout the experiment. Concentrations of calcitonin gene-related peptide (CGRP) in the plasma, the level of CGRP mRNA in dorsal root ganglia (DRG) and the density of CGRP immunoreactive (CGRP-ir) fibers in mesenteric artery were measured. Blood pressure was significantly elevated at day 10 postoperation (BP was 143+/-10 and 114+/-7 mm Hg for 2K1C and Sham groups, respectively, p<0.05). Treatment with capsaicin, which selectively depletes neurotransmitters in sensory nerves, enhanced hypertensive responses to clipping (BP was 168+/-7 and 143+/-10 mm Hg at day 10 postoperation for Cap1+2K1C and 2K1C groups, respectively, p<0.05), and BP in the rats treated with a second injection of capsaicin was greater than that in the rats treated with a single injection of capsaicin (At day 30 postoperation, BP was 199+/-7 and 166+/-9 mm Hg for Cap2+2K1C and 2K1C groups, respectively, p<0.01; mean arterial pressure was 185.2+/-6.6 and 150.5+/-4.1 mm Hg for Cap2+2K1C and 2K1C groups, respectively, p<0.01). The expression of alpha-CGRP mRNA in DRG (122.87+/-3.67 arbitrary units, p<0.05), the level of CGRP in the plasma (75.40+/-4.99 pg/ml, p<0.01) and the density of CGRP-ir fibers in mesenteric artery (525.67+/-31.42 intersections, p<0.05) were significantly increased in 2K1C rats. Treatment with capsaicin, a single injection or a second injection, prevented the increased in the expression of CGRP mRNA in DRG. However, the decreased level of CGRP was only observed in the rats treated with a second capsaicin. These results suggest that in 2K1C hypertensive rats, the activity of capsaicin-sensitive sensory nerves is increased, which is playing a compensatory depressor role to partially counteract the increase in blood pressure, and that the cardiovascular actions of CGRP is mediated by the alpha-CGRP isoform.     

Low pH medium induces calcium dependent release of CGRP from sensory nerves of guinea-pig dural venous sinuses.

Low pH medium has been shown to activate the 'efferent' function of capsaicin-sensitive primary sensory neurons. Calcitonin gene-related peptide (CGRP) is released from capsaicin-sensitive afferents of guinea-pig superior sagittal and transverse sinuses (SSTS), by capsaicin or bradykinin. Here, we report that low pH medium produces a remarkable release of CGRP from SSTS, which was dependent on the concentration of hydrogen ions of the medium (pH 7-5). Moreover, the pH 5-evoked release of CGRP-LI was markedly reduced (by about 70%) in a calcium-free medium containing 1 mM EDTA or abolished in samples pre-exposed to 10 microM capsaicin. The present observation that lowering of the pH promotes release of a powerful vasoactive peptide from perivascular capsaicin-sensitive sensory nerves may have some relevance in the pathophysiology of brain injury and migraine headaches.     

The indomethacin-induced gastric mucosal damage in rats. Effect of gastric acid,acid inhibition,capsaicin-type agents and prostacyclin

In pylorus-ligated rats subcutaneous (sc) pentagastrin (325.5 nmol/kg) or histamine (54.3 μmol/kg), but not the cholinergic linergic agent bethanechol (7.6 or 15.2 μmol/kg), increased gastric mucosal injury by sc indomethacin (55.8 μmol/kg). Intragastric (ig) administration of 0.15 or 0.3 N HCl greatly potentiated injury by sc indomethacin with widespread ulceration, intragastric bleeding and even perforation. The gastric mucosal damage produced by indomethacin plus 0.3 N HCl was reduced by ig capsaicin (3.1–25.1 μM), ig resiniferatoxin (0.38-6.1 μM), by sc atropine (0.15-1.2 μmol/kg) and to a lesser extent by ig prostacyclin (40–267 μM) or sc cimetidine (198.2 μmol/kg). The protective effect of capsaicin or resiniferatoxin was not prevented by atropine or cimetidine treatment. Capsaicin (6.5 mM) enhanced gastric injury by sc or ig indomethacin. Results indicate the importance of early vascular events in the pathogenesis of mucosal injury induced by indomethacin in the stomach and suggest a role for gastric acid in potentiation of such injury. Results further strengthen the idea of a protective role for capsaicin-sensitive sensory nerves in the stomach.     

Capsaicin-sensitive mechanisms in the modulation of rat colonic vascular permeability under physiological and pathological conditions

Inflammatory bowel disease (IBD) causes a prolonged life-quality reduction of patients and high costs for health services. The aim of this study was to explore the possible involvement of peptidergic capsaicin-sensitive afferent nerves (CSN) in the pathogenesis of IBD. For the defunctionalization of colonic CSN, the lower part of the colon (1–4 cm from the anus) was exposed through a midline laparotomy and small pieces of gelfoam moistened with a solution of capsaicin (1%, 100 μL) was applied onto the serosal surface for 30 min in male Wistar rats. Colonic vascular permeability was assessed by measuring the extravasation of [¹²⁵I] human serum albumin (2 μCi/kg, iv, 2 h prior to killing). Two months after capsaicin treatment a significant increase in albumin extravasation was found in the lower (P < 0.005), but not in the upper (5–8 cm from the anus) part of the colon as compared to the sham-operated control. Intrarectal (8 cm from anus) administration of trinitrobenzene-sulphonic acid (TNBS; 30 mg/rat) induced similar plasma leakage in the lower and upper colon of control (CSN-intact) rats (P < 0.001) 1 week later. TNBS + ethanol (50%) produced further extravasation throughout the colon (P < 0.001) of CSN-intact animals. In the lower colon of capsaicin-pretreated rats TNBS-alone provoked an increase in plasma extravasation (P < 0.001) similar to that caused by TNBS + ethanol in CSN-intact rats. In the upper colon there was no difference in the effect of TNBS-alone on plasma leakage between control (CSN-intact) and CSN-depleted rats. The results suggest that capsaicin-sensitive nerves may play a significant protective/anti-inflammatory role in the colon under normal and pathological conditions.     

Morphological and Functional Alterations of the Myenteric Plexus in Rats with TNBS-Induced Colitis

The 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced model of experimental colitis was used to investigate the time-course of alterations in enteric neurotransmission and/or smooth muscle function that occur in chronic inflammation. Myenteric plexus morphology (immunocytochemical markers), functional integrity of cholinergic neurons (³H-choline uptake, acetylcholine release and contractile response to electrical field stimulation) and smooth muscle integrity (contractile response to exogenous acetylcholine) were determined 2, 7, 15, and 30 days after TNBS treatment. In TNBS-treated rats extensive ulcerations of the mucosa and/or the submucosa and increase in colonic weights were accompanied by significant reduction in ³H-choline uptake, acetylcholine release and contractile response to stimulation of enteric nerves. These changes were maximal 7 and 15 days after TNBS treatment. Immunocytochemical marker (PGP 9.5, SNAP 25, synaptophysin and S100 protein) expression was absent in necrotic areas of colons removed 7 days post-injury and partially reduced in colons removed 15 days after TNBS treatment. By contrast, the contractile response to exogenous acetylcholine was significantly increased after 7 days in both inflamed and uninflamed regions and returned to control values by day 30. Likewise, an almost complete recovery of neural cholinergic function and of myenteric plexus morphology was observed 30 days after TNBS treatment. These data suggest that TNBS-induced colitis is associated with progressive and selective alterations in myenteric plexus structure and function, with consequent reduction of cholinergic neurotransmission and abnormality in colonic contractility. The reversibility of myenteric plexus disruption is a clear indication of neuronal plasticity within enteric nervous system as an adaptative mechanism against inflammatory challenges.     

Capsaicin-sensitive vagal afferents contribute to gastric acid and vascular responses to intracisternal TRH analog

Central injection of TRH or its stable analog, RX77368, produces a vagal cholinergic stimulation of gastric acid secretion, mucosal blood flow and motor function. In the present study, we have investigated the contribution of capsaicin-sensitive vagal afferent fibers to the gastric responses to intracisternal injection of RX77368. Gastric acid secretion, measured in acute gastric fistula rats anesthetized with urethane, in response to intracisternal injection of RX77368 (3-30 ng) was reduced by 21-65% by perineural pretreatment of the vagus nerves with capsaicin 10-20 days before experiments. The increase in gastric mucosal blood flow measured by hydrogen gas clearance induced by intracisternal injection of RX77368 (30 ng) was also reduced by 65% in capsaicin-pretreated rats. In contrast, increases in gastric motor function measured manometrically or release of gastric luminal serotonin in response to intracisternal injection of RX77368 (3-30 ng) were unaltered by capsaicin pretreatment. The mechanism by which vagal afferent fibers contribute to the secretory and blood flow responses to the stable TRH analog is unclear at present, but it is possible that the decrease in gastric mucosal blood flow by lesion of capsaicin-sensitive vagal afferents limits the secretory response.     

Enteroendocrine cells and 5-HT availability are altered in mucosa of guinea pigs with TNBS ileitis

Enteroendocrine cells act as sensory transducers, releasing 5-HT and numerous peptides that are involved in regulating motility, secretion, and gut sensation. The action of mucosal 5-HT is terminated by a 5-HT reuptake transporter (SERT). In this study, we examined the hypothesis that ileitis leads to changes in enteroendocrine cell populations and mucosal 5-HT availability. Ileitis was induced in guinea pigs by intraluminal injection of 2,4,6-trinitrobenzenesulfonic acid and experiments were conducted 3, 7, and 14 days after treatment. The number of somatostatin, neurotensin, and 5-HT-immunoreactive cells increased at 3 and 7 days of ileitis, respectively, whereas no significant changes in the numbers of cholecystokinin, glucagon-like peptide-2, glucose-dependent insulinotropic peptide, and peptide YY-immunoreactive cells were observed. Chemical stimulation of the inflamed mucosa with sodium deoxycholic acid significantly increased 5-HT release compared with basal release. Mechanical stimulation of the mucosa potentiated the effect of the chemical stimuli at day 7. Epithelial SERT immunoreactivity was significantly reduced during the time course of inflammation. Thus changes in enteroendocrine cell populations and 5-HT availability could contribute to the altered motility and secretion associated with intestinal inflammation by disrupting mucosal signaling to enteric nerves involved in peristaltic and secretory reflexes.     

TNBS-induced inflammation modulates the function of one class of low-threshold rectal mechanoreceptors in the guinea pig

The effects of trinitrobenzene sulfonic acid (TNBS)-induced inflammation on specialized, low-threshold, slowly adapting rectal mechanoreceptors were investigated in the guinea pig. Under isoflurane anesthesia, 300 microl saline or TNBS (15 mg/ml) in 30% ethanol was instilled 7 cm from the anal sphincter. Six or 30 days later, single unit extracellular recordings were made from rectal nerve trunks in flat-sheet in vitro preparations attached to a mechanical tissue stretcher. TNBS treatment caused macroscopic ulceration of the rectal mucosa at 6 days, which fully resolved by 30 days. Muscle contractility was unaffected by TNBS treatment. At 6 days posttreatment, responses of low-threshold rectal mechanoreceptors to circumferential stretch were increased, and the proportion of afferents responding with von Frey hair thresholds 相似文献   

Capsaicin-sensitive adrenal sensory fibers participate in compensatory adrenal growth in rats

Compensatory adrenal growth, in which one gland undergoes hyperplasia after removal of the other, is mediated by a neural reflex. In the present studies, a method employing capsaicin to selectively remove adrenal sensory fibers was developed and applied to determine whether adrenal capsaicin-sensitive fibers participate in compensatory adrenal growth. The splanchnic nerves of anesthetized male rats were treated with capsaicin or vehicle. Capsaicin treatment selectively removed adrenal calcitonin gene-related peptide-positive fibers. One week after drug treatment, rats underwent left adrenalectomy or sham surgery and recovered for 5 days. Capsaicin treatment bilaterally or to the left splanchnic nerve alone (i.e., the afferent nerve in the reflex) impaired compensatory adrenal growth at 5 days compared with vehicle controls, whereas capsaicin treatment to the right splanchnic nerve alone did not affect growth. Moreover, left adrenalectomy induced c-Fos immunolabeling in ipsilateral dorsal spinal cord that was prevented by capsaicin treatment. These data suggest that adrenal capsaicin-sensitive afferent nerves participate in compensatory adrenal growth and that this effect is primarily on the afferent limb of the reflex.     

Capsaicin and the stomach. A review of experimental and clinical data

Capsaicin, the pungent principle of hot pepper, because of its ability to excite and later defunctionalize a subset of primary afferent neurons, has been extensively used as a probe to elucidate the function of these sensory neurons in a number of physiological processes. In the rat stomach, experimental data provided clear evidence that capsaicin-sensitive (CS) sensory nerves are involved in a local defense mechanism against gastric ulcer. Stimulation of CS sensory nerves with low intragastric concentrations of capsaicin protected the rat gastric mucosa against injury produced by different ulcerogenic agents. High local desensitizing concentrations of capsaicin or systemic neurotoxic doses of the agent markedly enhanced the susceptibility of the rat gastric mucosa to later noxious challenge. Resiniferatoxin, a potent analogue of capsaicin possesses an acute gastroprotective effect similar to that of capsaicin in the stomach. The gastroprotective effect of capsaicin-type agents involves an enhancement of the microcirculation effected through the release of mediator peptides from the sensory nerve terminals with calcitonin gene-related peptide being the most likely candidate implicated. They do not depend on vagal efferent or sympathetic neurons or involve prostanoids. The gastric mucosal protective effect of prostacyclin is retained after systemic or topical capsaicin desensitization. Capsaicin-sensitive fibers are involved in the repair mechanisms of the gastric mucosa. A protective role for CS sensory nerves has also been demonstrated in the colon. In most studies, capsaicin given into the stomach of rats or cats inhibited gastric acid secretion. In humans, although recent studies provide evidence in favor of a beneficial effect of capsaicin on the gastric mucosa, an exact concentration-related assessment of the effect of the agent is still lacking.     

Bile acid-induced secretion in polarized monolayers of T84 colonic epithelial cells: Structure-activity relationships

Bile acid epimers and side-chain homologues are present in the human colon. To test whether such bile acids possess secretory activity, cultured T84 colonic epithelial cells were used to quantify the secretory properties of synthetic epimers and homologues of deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). In our study, chloride secretion was measured as changes in short-circuit current (DeltaI(sc), in microA/cm2) with the use of voltage-clamped monolayers of T84 cells mounted in Ussing chambers. Bile acids were added at 0.5 mM, a concentration that did not alter transepithelial resistance. Data were expressed as peak DeltaI(sc) (means +/- SD). When added bilaterally, DCA stimulated a DeltaI(sc) response of 15.7 +/- 12.5 microA/cm2. The 12beta-OH epimer of DCA was less potent (DeltaI(sc) = 8.0 +/- 1.7 microA/cm2), whereas its 3beta-OH epimer had no effect. CDCA stimulated secretion (DeltaI(sc) = 8.2 +/- 5.5 microA/cm2), whereas both its 7beta-OH and 3beta-OH epimers were inactive, as was lithocholic acid. HomoDCA (1 additional side-chain carbon) was active (DeltaI(sc) = 7.8 +/- 4.8 microA/cm2), whereas norDCA (1 fewer carbon) and dinorDCA (2 fewer carbons) were not. Taurine conjugates of DCA and CDCA stimulated secretion (DeltaI(sc) = 12.3 +/- 7.5 and 8.8 +/- 4.8 microA/cm2, respectively) from the basolateral side but not the apical side. Uptake of taurine conjugates from the basolateral but not the apical side was shown by mass spectrometry. These studies indicate marked structural specificity for bile acid-induced chloride secretion and show that modification of bile acid structure by colonic bacteria modulates the secretory properties of these endogenous secretagogues.     

Proliferative capacity of enterochromaffin cells in guinea-pigs with experimental ileitis

Enterochromaffin (EC) cells regulate gut motility and secretion in response to luminal stimuli, via the release of serotonin (5-HT). Inflammatory bowel disease and other gastrointestinal disorders are associated with increased numbers of EC cells and 5-HT availability. Our aim was to determine whether proliferation of EC cells contributed to the hyperplasia associated with intestinal inflammation. Ileitis was induced in guinea-pigs by intraluminal injection of 2,4,6-trinitrobenzene sulphonic acid (TNBS). A single pulse of 5-bromo-2′-deoxyuridine (BrdU) was injected 1 or 24 h before the collection of tissue, 6 or 7 days after TNBS treatment. In the controls, the labelling index (percentage of BrdU-labelled EC cells) was less than 1%. Despite a significant increase in EC cells in the inflamed ileum, the labelling index was similar in the TNBS-treated animals to that of controls. An increased occurrence of EC cells in the BrdU-labelled zone accounted for the increase in EC cells in the inflamed ileum. Goblet cell numbers were also significantly increased in the inflamed ileum, indicating that cell hyperplasia was not limited to the enteroendocrine cell lineage. This study demonstrates that a small portion of EC cells retain some proliferative capacity; however, hyperplasia associated with ileitis is not attributable to the increased proliferation of EC cells and is not limited to one cell lineage. Therefore, EC cell hyperplasia most probably occurs at the level of the stem cell or recruitment from the progenitor pool. This work was supported by an operating grant from the Crohn’s and Colitis Foundation of Canada (CCFC; to Keith Sharkey and Dr. Gary Mawe, University of Vermont, USA). Keith Sharkey is an Alberta Heritage Foundation for Medical Research (AHFMR) Medical Scientist and the CCFC Chair in Inflammatory Bowel Disease Research. Jennifer O’Hara is an AHFMR graduate student.     

Role of capsaicin-sensitive nerve fibers in uterine contractility in the rat

The possible participation of capsaicin-sensitive sensory nerves in the modulation of neurogenic contractions was studied in nonpregnant and term pregnant rat uteri. Neurogenic contractions were elicited by electric field stimulation (40 V, 1-70 Hz, 0.6 msec) in intact uteri and uteri that were previously exposed to capsaicin in vitro. In capsaicin pretreated preparations obtained both from nonpregnant and term pregnant rats, a dose-dependent increase in the amplitude of uterine contractions was detected. Prior systemic treatment of the rats with capsaicin (130 mg/kg, s.c.) abolished the effect of in vitro capsaicin administration on the amplitude of neurogenic contractions. Use of a specific antagonist of calcitonin gene-related peptide revealed that depletion of this peptide, which normally elicits uterine smooth muscle relaxation, may be responsible for the increased responsiveness of the uterus to low-frequency stimulation. Experiments on the localization of calcitonin gene-related peptide in uterine tissue specimens exposed to capsaicin revealed dose-dependent depletion of calcitonin-gene related peptide-immunoreactive nerves innervating blood vessels and the myometrium. The findings indicate 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 nerve activation may be part of a trigger mechanism leading to preterm contractions evoked by, for example, inflammation.     

Reflex control of the cutaneous circulation after acute and chronic local capsaicin.

To investigate whether local activity of capsaicin-sensitive sensory afferents in the skin has a modulatory role in the reflex cutaneous vasodilator response to hyperthermia in humans, experiments were conducted in two parts. First, low-dose topical capsaicin (0.025%) was administered acutely to stimulate local activity of these afferents. Second, we temporarily desensitized these nerves in a small area of skin using chronic capsaicin treatment (0.075% for 7 days). Each intervention was followed by whole body heating using water-perfused suits and then by local warming to 42 degrees C for assessment of maximum cutaneous vascular conductance. Skin blood flow was measured by laser-Doppler flowmetry and divided by mean arterial pressure (Finapres) for assessment of cutaneous vascular conductance. Maximum vascular conductance was not influenced by either acute or chronic capsaicin treatment (P > 0.10). After acute capsaicin, baseline cutaneous vascular conductance was elevated above that at control sites (25.34 +/- 6.25 vs. 10.57 +/- 2.42%max; P < 0.05). However, internal temperature thresholds for vasodilation were not affected by either acute or chronic capsaicin (P > 0.10). Furthermore, neither acute (control: 112.74 +/- 36.83 vs. acute capsaicin: 96.92 +/- 28.92%max/ degrees C; P > 0.10) nor chronic (control: 142.45 +/- 61.89 vs. chronic capsaicin: 132.12 +/- 52.60%max/ degrees C; P > 0.10) capsaicin administration influenced the sensitivity of the reflex cutaneous vasodilator response. We conclude that local activity of capsaicin-sensitive afferents in the skin does not modify reflex cutaneous vasodilation during hyperthermia.     

Small doses of capsaicin given intragastrically inhibit gastric basal acid secretion in healthy human subjects.

Although the direct inhibitory effect of small dose of capsaicin on gastric secretory responses was proved in animal observations, the role of capsaicin-sensitive afferent nerves (CSAN) and the effect of capsaicin applied in small and high doses on gastric secretion in human has not been clarified yet. In this study we investigated the influence of different small doses (100-800 microg) of capsaicin given intragastrically through an orogastric tube on gastric basal secretory responses in 10 healthy human subjects. Gastric basal secretory responses (volume, H+-concentration, H+-output) were measured from the suctions of gastric juice for a 1-h period. It has been found that: a) capsaicin dose-dependently inhibited the volume and H+-output of gastric juice; b) ID50 was found to be about 400 microg for capsaicin on gastric acid secretion; c) the time interval for capsaicin-induced gastric inhibition existed for about 1 h indifferently from the higher dose (800 microg) of capsaicin given after. It has been concluded that the capsaicin (given in small doses) inhibits the gastric basal acid output via stimulation of the inhibition of capsaicin sensitive afferent nerves.     

The response of the blood proteins to ablation of the capsaicin-sensitive nerves

Effects of neurotoxic doses of capsaicin (150 mg/kg) on the protein content in electrophoretic fractions (PAAG) in the Wistar rat plasma were studied. In early period (7 days) after administration of capsaicin, an increase of the alpha1-, alpha2-globulins and a decrease of the albumin, gamma-globulins, were observed. After 14-30 days, increase of the albumin and decrease of the alpha1-, gammay-globulins were detected. The ablation of the capsaicin-sensitive nerves abrogated the changes of positive and negative acute phase reactants induced by zymosan and diminished the content of gamma-globulins.