Capsaicin-sensitive Fibers Research Articles

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.

Submodality-selective hyperalgesia adjacent to partially injured sciatic nerve in the rat is dependent on capsaicin-sensitive afferent fibers and independent of collateral sprouting or a dorsal root reflex.

We studied submodality dependence of sensory changes produced by unilateral ligation of the sciatic or the saphenous nerve in the rat. We focused especially on sensory changes in the skin area adjacent to the innervation area of the injured nerve. Moreover, we examined the roles of capsaicin-sensitive nociceptive fibers, collateral sprouting and a dorsal root reflex in sensory changes observed behaviorally. Assessment of sensory changes was performed by a pattern of behavioral tests: hot-plate test and hindlimb withdrawal responses induced by radiant heat, hot-water bath, innocuous mechanical stimuli, and noxious mechanical stimuli. In one group, the saphenous nerve ipsilateral to the sciatic ligation was topically treated with capsaicin (1%) at the time of the surgery. A proximal stump of a saphenous nerve strand was orthodromically stimulated to induce a dorsal root reflex (an antidromic volley) in nociceptive fibers of the saphenous nerve trunk. For visualization of plasma extravasation induced by a dorsal root reflex, a dye-labeling (Evans blue) technique was used. A collateral sprouting of nociceptive fibers of the uninjured saphenous nerve was evaluated by determining the plasma extravasation response induced by antidromic stimulation of the saphenous nerve. Three and 10 days following the sciatic constriction injury, the hindlimb withdrawal threshold evoked by noxious mechanical stimulation of the medial side of the paw (the innervation are of the intact saphenous nerve) was significantly decreased. There was no corresponding thermal hyperalgesia adjacent to the injured sciatic nerve. Chronic constriction of the saphenous nerve did not produce any significant hyper- or hypoalgesia to mechanical or thermal stimulation of the uninjured sciatic nerve area. Topical treatment of the ipsilateral (intact) saphenous nerve at the time of the sciatic nerve ligation completely prevented the development of mechanical hyperalgesia in the medial side of the paw (the innervation area of the saphenous nerve). No dorsal root reflex in nociceptive fibers mediating the adjacent hyperalgesia could be evoked. No collateral sprouting of the uninjured nociceptive fibers of the saphenous nerve was observed. The results indicate that the constriction injury of the sciatic nerve produced a selective hyperalgesia to mechanical stimulation in the innervation area of the neighboring saphenous nerve. At the peripheral level, the mechanical hyperalgesia adjacent to the innervation area of the injured nerve was mediated by capsaicin-sensitive nociceptive fibers. Collateral sprouting of nociceptive fibers from the uninjured to the injured innervation area did not contribute to the present sensory findings. The sciatic nerve injury did not induce a dorsal root reflex in nociceptive fibers innervating the hyperalgesic saphenous nerve area.

Effect of capsaicin and resiniferatoxin on gastrointestinal blood flow in rats

The effect of capsaicin and resiniferatoxin on gastrointestinal blood flow was studied in anaesthetized rats by laser Doppler flowmetry. Resiniferatoxin injected into the jugular vein (0.08–1.6 nmol/kg) produced a marked and dose-dependent increase in gastric blood flow, while the effect of capsaicin (0.33–19.6 nmol/kg) was transient, variable and accompanied by profound systemic blood pressure changes. After acute bilateral cervical vagotomy combined with sympathetic neurone blockade (guanethidine 16 μmol/kg) or α-adrenoceptor blockade (phentolamine 1.6 μmol/kg), the vasodilator response to injected resiniferatoxin was more pronounced, indicating that the resiniferatoxin-induced gastric vasodilatation is not due to reflexes via parasympathetic or sympathetic efferent fibres. Resiniferatoxin given i.v. (0.08–0.64 nmol/kg) evoked a similar increase in the blood flow of the jejunum. Capsaicin (0.33–33 μM) or resiniferatoxin (0.16–1.6 μM) applied topically to the serosal surface of the stomach or jejunum produced a pronounced and long-lasting increase in blood flow after vagotomy and guanethidine treatment. The blood flow and blood pressure responses to capsaicin and resiniferatoxin were absent in rats desensitized with systemic capsaicin pretreatment. These laser Doppler data provide the first evidence for the effect of resiniferatoxin on gastrointestinal microcirculation and indicate the advantages of this agent and technique to study the sensory-efferent function of capsaicin-sensitive fibres.

Sensory denervation with capsaicin attenuates inflammation and nociception in arthritic rats

The relatively few studies that have investigated the effects of the nervous system on chronic joint disease have reported conflicting results. We have reassessed the effects of capsaicin on experimental polyarthritis with particular reference to the relationship between changes in nociception and changes in process and outcome measures of disease activity. Capsaicin pretreatment significantly attenuated both joint swelling and disease outcome as determined by quantitative radiology and histology. There was a close correlation between process measures of inflammation and mechanical hyperalgesia in both the untreated and capsaicin treated arthritic groups. The results confirm a suppression of inflammation by capsaicin and imply that the nociceptive and pro-inflammatory (neurogenic inflammation) activities of capsaicin-sensitive fibres are closely linked such that stimuli which cause pain will also induce neurogenic inflammation and vice versa.

Critical role of the capsaicin-sensitive nerve fibers in the development of the causalgic symptoms produced by transecting some but not all of the nerves innervating the rat tail

We investigated the role of capsaicin-sensitive small diameter fibers in the development of the thermal and mechanical allodynia in a new rat model for neuropathic pain, produced by transecting some but not all of the nerves innervating the tail. Capsaicin (50 mg/kg, s.c.) injected neonatally prior to the nerve injury produced thermal hypoalgesia in the tail the degree of which was variable across individual rats, presumably as a result of variable degeneration of the small diameter fibers. When subjected to the nerve injury, the animals with moderate thermal hypoalgesia exhibited signs of pain (e.g., tail flick) to normally innocuous mechanical stimuli applied to the tail with von Frey hairs (4.9 mN or 19.6 mN bending force), but not to thermal stimuli given by immersion of the tail into cold (4 degrees C) or warm (40 degrees C) water. The animals with marked thermal hypoalgesia, on the other hand, exhibited no signs of pain either to the mechanical or to the thermal stimuli. These results suggest that the capsaicin-sensitive fibers are critical in the development of both the mechanical and thermal allodynia. It is hypothesized that the destruction of A delta- and C-nociceptive fibers by capsaicin prevented activities induced in these fibers by the nerve injury from producing a central sensitization and thus allodynia.

Antinociceptive effect of intrathecally administered pituitary adenylate cyclase activating polypeptide (PACAP) on the rat formalin test

It has been reported that pituitary adenylate cyclase activating polypeptide (PACAP) is a sensory neuropeptide and that it is contained in capsaicin sensitive fibers. PACAP occurs as two variants, PACAP27 and the C-terminally extended PACAP38. We examined the effect of intrathecally administered PACAP27 and PACAP38 on the rat formalin test which is considered to be a model of animal pain induced by inflammation. Fifty microliters of 5% formalin was injected subcutaneously in the plantar surface of the right hind paw. To analyze the effect of PACAP27 and PACAP38, the instances of spontaneous flinching were counted. Administration of either PACAP27 or PACAP38 resulted in a monotonically dose-dependent reduction in the instances of flinching behavior. These results suggested that PACAP may play an important role in inhibiting the transmission of the nociceptive information evoked by inflammation.

Effect of capsaicin on release of substance P-like immunoreactivity from vascularly perfused rat duodenum.

The release of substance P-like immunoreactivity (SPLI) from the rat duodenum was investigated using an in situ vascularly perfused preparation. Results show that the basal release of SPLI was measurable and significantly enhanced by the administration of both 1,3, and 10 microM of capsaicin, indicating that SPLI is present in capsaicin-sensitive afferent nerve fibers. It is concluded that the present model may be useful for the study of the control of duodenal release of SPLI.

Nitric oxide formation is involved in vagal inhibition of the stomach of the trout ( Salmo gairdneri)

Stimulation of the vagus nerves to isolated stomach preparations from trout ( Salmo gairdneri) caused both excitation and inhibition of smooth muscle activity. Excitatory responses were partly reduced by atropine, suggesting that cholinergic neurons are involved. The atropine-resistant excitation could not readily be ascribed to a ‘rebound’ from preceding inhibition, to the production of prostaglandins, or to the activation of either adrenergic or capsaicin-sensitive fibres. Inhibitory responses were reduced by the nicotinic antagonist d-tubocurarine and more profoundly reduced by an inhibitor of nitric oxide synthase, N G-nitro- l-arginine . The latter effect was reversed by excess l-arginine. The nitric oxide donors sodium nitroprusside and nitroglycerine caused inhibition of the muscle. It is concluded that the vagal inhibitory postganglionic neurons are nitrergic in this tissue.

Axon reflex vasodilatation in cat dental pulp elicited by noxious stimulation of the gingiva.

Antidromic stimulation of sensory nerves has been shown to increase blood flow in the tissue they innervate. This study was designed to determine if antidromic vasomotor responses occur in feline dental pulp and if they are mediated by branched axons supplying both tooth pulp and gingiva. Dynamic changes in pulpal blood flow (PBF) elicited by electrical stimulation, pinching, heating, and capsaicin application to the gingivae were investigated in cat mandibular canine teeth by means of Laser Doppler Velocimetry. All inferior alveolar nerve bundles and the cervical sympathetic trunk had been previously sectioned to avoid the occurrence of brainstem reflexes, e.g., somato-autonomic vasomotor reflexes. Increases in PBF were observed in seven out of 12 cats when a restricted gingival area adjacent to the canine teeth was stimulated as described, but the increases were abolished after the sensitive gingival area was painted with lidocaine jelly, a surface anesthetic. These vasodilator responses, remarkably reduced following repeated application of 30 mM of capsaicin, are considered to be induced via antidromic activation of capsaicin-sensitive nociceptive nerve fibers, presumably by axon reflex mechanisms, suggesting that nerve terminals supplying the gingiva originate from parent axons which have collaterals that innervate the canine tooth pulp.

Central vagal activation by TRH induces gastric hyperemia: role of CGRP in capsaicin-sensitive afferents in rats.

The role of calcitonin gene-related peptide (CGRP) in the vagal cholinergic-mediated increase in gastric mucosal blood flow (GMBF) induced by the stable thyrotropin-releasing hormone (TRH) analogue RX-77368 injected intracisternally (ic, 30 ng) was investigated in urethan-anesthetized rats using the hydrogen gas clearance technique. alpha-CGRP (14 micrograms.kg-1.h-1) or bethanechol (150 micrograms.kg-1.h-1) infused close intra-arterially to the stomach or RX-77368 injected intracisternally increased GMBF by 76, 102, and 131%, respectively, 30 min after administration. The CGRP antagonist, human CGRP-(8-37) [hCGRP-(8-37)], injected intravenously (15 micrograms/kg bolus and 3 micrograms.kg-1.h-1) inhibited by 100, 97, and 73% the gastric hyperemic response to alpha-CGRP, TRH analogue, and bethanechol, respectively, whereas the substance P antagonist CP-96,345 (3 mg/kg iv) had no effect. In capsaicin-pretreated rats, hCGRP-(8-37) no longer blocked the increase in GMBF induced by intracisternal RX-77368. These results suggest that the gastric hyperemic response to central vagal activation induced by intracisternal TRH analogue at 30 ng is mediated by local effector function of capsaicin-sensitive afferent fibers releasing CGRP.

Intracisternal thyrotropin‐releasing hormone‐induced vagally mediated gastric protection against ethanol lesions: Central and peripheral mechanisms

The vagus is involved in mediating gastric cytoprotection and adaptive cytoprotection. However, the central and peripheral mechanisms through which the vagus expresses its action are still poorly known. Medullary thyrotropin-releasing hormone (TRH) plays an important role in the vagal regulation of gastric function. The stable TRH analogue, RX 77368, micro-injected into the cisterna magna or the dorsal motor nucleus (DMN) of the vagus at a dose that did not influence gastric acid secretion prevented gastric injury induced by intragastric administration of 60% ethanol in conscious or urethane-anaesthetized rats. The cytoprotective action of TRH is mediated through vagal cholinergic release of prostaglandin E2 (PGE2). Prostaglandin E2 action is unrelated to changes in gastric mucosal blood flow (GMBF). In addition, other peripheral mechanisms involve calcitonin gene-related peptide (CGRP) contained in capsaicin sensitive afferent fibres and nitric oxide, both of which mediate the associated increase in GMBF induced by intracisternal injection of RX 77368. These data indicate that medullary TRH induces vagally mediated gastric protection against ethanol lesions. Its action is expressed through the muscarinic dependent release of PGE2 and nitric oxide, and efferent function of capsaicin-sensitive afferent fibres releasing CGRP.

Possible involvement of capsaicin-sensitive sensory nerves in the regulation of cochlear blood flow in the guinea pig.

Capsaicin-induced microcirculatory changes in the cochlea of anaesthetized guinea pigs were examined by laser-Doppler flowmetry. Close intraarterial capsaicin infusion into the anterior inferior cerebral artery at doses of 10-50 pmol/min was followed by dose-dependent vasodilatation. Capsaicin infused in a dose of 150-200 pmol/min or above resulted in vasoconstriction in the region examined. Topical capsaicin administration into the cochlea (50-150 pmol) resulted in very moderate vasodilation with a latency of 1-2 min. Perivascular capsaicin application onto the anterior inferior cerebellar artery elicited an elevated blood flow in the cochlea, too. It is concluded that the release of vasoactive substances from capsaicin-sensitive nerve fibres in the inner ear of the guinea pig may play a role in the control of the local microcirculation. These nerves may also be involved in the neurogenic inflammatory processes in the region.

Reflex vasodilatation in the cat lip elicited by stimulation of nasal mucosa by chemical irritants

Local application of capsaicin (threshold dose 150 microM) or nicotine (threshold dose 15 mM) to the nasal mucosa as well as electrical stimulation (threshold intensity 10 V) of the nasal mucosa elicited dose- or intensity-dependent blood flow increases in the ipsilateral lower lips of the anesthetized cats. Pretreatment with 3 mM capsaicin applied locally to the nasal mucosa abolished or reduced the vasodilation in response to capsaicin, nicotine, and ammonia vapor but not to light mechanical or electrical stimulation of the nasal mucosa. The blood flow increases elicited by all above stimuli were greatly reduced by pretreatment with hexamethonium, an autonomic ganglion blocker. These results suggest that stimulation of the nasal mucosa by chemical (capsaicin, nicotine, ammonia), mechanical, or electrical methods elicits the autonomic reflex vasodilatation in the cat lower lips. Furthermore, there seem to be at least two types of afferent fibers in the nasal mucosa of the cats: one type is capsaicin-sensitive fibers, while another type is capsaicin-resistant fibers involved in reflex vasodilatation.

Gastric hyperemia accompanying acid secretion is not mediated by sensory nerves

It is not known how the signal to increase gastric mucosal blood flow is passed from the gastric parietal cell layer to the resistance vessels in the submucosa. We tested the hypothesis that mucosal hyperemia accompanying stimulated gastric acid secretion is mediated by capsaicin-sensitive sensory nerves. Rats were denervated by systemic capsaicin treatment (125 mg/kg, subcutaneously, 10-14 days prior to experimentation). Acid secretion was stimulated by intravenous pentagastrin (4, 12, and 36 micrograms/kg/hr) and was measured by a continuous perfusion method. Mucosal blood flow was measured by the hydrogen gas clearance method. Sensory denervation did not affect basal blood pressure, gastric acid secretion, or mucosal blood flow. In control rats, increases in gastric mucosal blood flow and acid secretion were dose-related. With denervation, not only was there no inhibition of the blood flow response to acid secretion, but the dose-dependent rise in acid secretion was accompanied by increased mucosal blood flow that was out of proportion to the acid secretory response. The capsaicin-sensitive afferent fibers do not transmit the signal to increase gastric mucosal blood flow in response to stimulated acid secretion. It appears that sensory nerves modulate but do not mediate the mucosal hyperemic response to acid secretion.

Evidence that removal of capsaicin accelerates desensitization on the tongue

It has previously been shown that repeated presentations of a moderate concentration of capsaicin could either sensitize or desensitize the tongue, depending upon the temporal pattern of stimulation. Only when stimulation was halted for 5 min or longer did sensitization begin to give way to desensitization. The apparent necessity of a hiatus in stimulation led to the hypothesis that desensitization involved an inability to re-excite quiescent fibers rather than a progressive suppression of stimulated fibers. This hypothesis was tested in the present study by measuring the perceptual response to a non-desensitizing irritant, zingerone, when it was presented at the rate of l/min following a series of capsaicin conditioning stimuli. After an initial, brief period of cross- hyper-sensitization, cross-desensitization developed at a rate equivalent to that observed when no stimulus was presented. Thus, the results disproved the hypothesis that desensitization cannot occur if capsaicin-sensitive fibers continue to be stimulated, and suggested that after an initial period of excitation, the removal of capsaicin accelerates the desensitization process. This seeming paradox is discussed in terms of the neural mechanisms that may underlie capsaicin desensitization.

Sensory irritation and taste produced by NaCl and citric acid: effects of capsaicin desensitization

Three experiments were conducted to measure the sensory irritation produced by two prototypical gustatory stimuli: citric acid and NaCl. The stimuli were applied to the tip of the tongue on filter paper disks. The first experiment revealed that solutions of NaCl and citric acid that produced approximately equal taste sensations also produced similar amounts of irritation; that the psychophysical functions for irritation were approximately twice as steep as the functions for taste; and that irritation grew over time for NaCl but not for citric acid. When viewed as a percentage of the taste sensation at 25 s, NaCl irritation averaged 23% at the lowest concentration and 70% at the highest concentration; citric acid irritation averaged 44% at the lowest concentration and 98% at the highest concentration. The second experiment investigated whether the irritation produced by these two stimuli was mediated via capsaicin-sensitive (CS) fibers. The experiment included a pre-test, an irritation treatment with either capsaicin (a desensitizing agent) or zingerone (a non-desensitizing agent), a 15 min rest period and a post-test. Reductions in irritation and taste occurred following treatment with both capsaicin and zingerone. A third experiment demonstrated that the majority of the effect of zingerone on taste and irritation was due to a perceptual context effect. After the context effect was taken into account, capsaicin desensitization remained significant for both salt taste and salt irritation at the highest concentration. A similar pattern of results for citric acid suggests that both citric acid and NaCl produce irritation in part via CS fibers. The results are discussed in terms of the ability of subjects to discriminate the gustatory and chemesthetic components of oral sensations and the role of salt and acid irritation in flavor perception.

Involvement of calcitonin gene-related peptide in rat experimental colitis

This study investigated the role of capsaicin-sensitive fibers on trinitrobenzensulphonic acid (TNB)-induced colitis in rats. Capsaicin pretreatment (164 + 164 μmol/kg sc in 2 days) produced an increase of damaged area and colon wet weight at 24 h and 1 week after the challenge. On the other hand, acute stimulation of sensory nerves by local application of capsaicin (1.2–60 μmol/kg) as well as exogenous administration of CGRP (2.6–26.3 nmol/kg sc) ameliorated the lesions and reduced the increase of colon weight in TNB-colitis. The protective effect of acute capsaicin (7.7 μmol/kg) was transient and lost in capsaicin-desensitized animals, showing its specificity and the likely participation of acute release of peptides in this mechanisms. Moreover, development of TNB colitis was associated with a selective decrease in tissue CGRP-like immunoreactivity. These findings provide evidence that capsaicin-sensitive nerves, probably via the release of protective neurotransmitters such as CGRP, play a defensive role in colitis.

Acute intragastric application of capsaicin inhibits 2-deoxy-D-glucose — but not histamine-induced gastric acid secretion in the dog

In this study the influence of acute exposure of gastric mucosa to the sensory neurotoxin capsaicin on basal gastric acid secretion and on secretion induced by 2-deoxy-D-glucose or histamine in conscious dogs with gastric fistulae has been investigated. Under basal conditions intragastric capsaicin (160 μM, 50 ml of volume) did not induce any significant change in acid secretion and in plasma levels of gastrin. Total acid output induced by 2-deoxy-D-glucose (75 mg/kg i.v.) was significantly decreased by intragastric application of capsaicin, while plasma gastrin concentrations were unaffected. A direct stimulant of the parietal cells, such as histamine (64 μg/kg s.c.) increased gastric acid secretion which was not sensitive to capsaicin pretreatment. These findings indicate the involvement of capsaicin-sensitive fibers in the control of vagally-induced gastric acid secretion in the dog.

Neurogenic inflammation and the oral mucosa.

Since the rôle of neurogenic inflammation in various pathological conditions is well-established, we presume that it also has great importance in the development of several inflammatory processes in the oral mucosa. In the course of experimentally-induced neurogenic inflammation of the oral mucosa in rats, vasodilation and plasma extravasation occur in the area supplied by unmyelinated capsaicin-sensitive fibres. Upon activating these fibres in the oral mucosa, mediators such as histamine, substance P (SP) and calcitonin gene related peptide (CGRP) are released from the peripheral terminals of afferent nerves causing characteristic symptoms of neurogenic inflammation. By histochemical techniques, SP- and CGRP-immunoreactive fibres have occurred in the area of the rat oral mucosa stimulated mostly in the free and attached gingiva around the molar teeth in the lower jaw. Capsaicin pretreatment performed neonatally or at adult age causes a loss of SP-immunoreactive fibres and prevents the vasodilatory responses, as well as the increase in vascular permeability elicited by the antidromic stimulation of the inferior alveolar nerve. As the transection of inferior alveolar nerve decreased the extravasation of Evans blue on the ipsilateral side and did not affect the capsaicin-induced enhancement in blood flow, we suggest that the two symptoms of the inflammation, i.e., the increased vascular permeability and decreased vascular resistance, should be produced by different mechanisms. The results of all the morphological and functional studies seem to confirm the possibility that there is an important neurogenic component of the inflammatory alterations caused by different mechanical and chemical stimuli in the oral mucosa.

Gastric acid secretory responses induced by peptone are mediated by capsaicin-sensitive sensory afferent neurons.

The involvement of capsaicin-sensitive afferent neurons in modulating acid-secretory responses to peptone, a product of protein digestion, has been investigated in the continuously perfused stomach of the urethan-anesthetized rat. Systemic neonatal pretreatment with capsaicin, which destroys primary afferent neurons, does not modify basal levels of acid secretion. Acid responses to intragastric perfusion with isotonic (0.5, 1, and 2.4%) or hypertonic (10 and 20%) solutions of peptone were reduced in capsaicin-treated rats. Intragastric perfusion with hypertonic mannitol (18%) did not stimulate secretion of acid. Systemic capsaicin pretreatment did not modify acid responses to intraperitoneal histamine (5 mg/kg) or pentagastrin (100 micrograms/kg). Acute intragastric perfusion (10 min) with capsaicin (0.3 mg/ml), tetrodotoxin (150 ng/ml), or the combination of both neurotoxins reduced the acid responses to 1% peptone to levels not different from those of animals treated systemically with capsaicin. Bilateral vagotomy or acute celiac ganglionectomy also decreased acid responses to 1% peptone in control animals, without modifying the diminished responses to peptone in rats treated systemically with capsaicin. Gastric acid secretory responses in rats undergoing both vagotomy and celiac ganglionectomy were not lower than those obtained after each surgical procedure alone. These findings suggest that peptone stimulates acid secretion in the rat partially by activating a nervous reflex mediated by capsaicin-sensitive sensory afferent fibers. The reflex arc involves fibers that would terminate in the gastric mucosa and project to, or from, the central nervous system through the vagus and the celiac ganglion.