Capsaicin In Rats Research Articles

Characterization of Gastric Mucosal Blood Flow Response Induced by Intragastric Capsaicin in Rats

Gastric mucosal blood flow (GMBF) was measured in the ex vivo stomachs of anesthetized rats simultaneously with mean arterial blood pressure (MBP), luminal pH and transmucosal potential difference (PD) in an attempt to characterize these responses induced by capsaicin. The stomach was mounted on a Lucite chamber, perfused with saline at the flow rate of 1 ml/min, and GMBF was measured by Laser flowmetry. Under these conditions, the pH, PD and GMBF were 3.5 to 4.0, -30 to -35 mV and 8-12 ml/min/100 g, respectively. Mucosal application of capsaicin (0.03 - 1 mg/ml for 10 min) increased GMBF in a concentration-dependent manner, without any change in PD, pH and MBP. The increased GMBF response caused by capsaicin was abolished by chemical deafferentation following systemic capsaicin injections (total dose: 100 mg/kg), significantly attenuated by pretreatment with indomethacin (5 mg/kg, s.c.) or ruthenium red (300 micrograms/kg, i.v.), but was not affected by spantide (100 micrograms/kg, i.v.), atropine (300 micrograms/kg, i.p.) or disodium cromoglycate (30 mg/kg, i.p.). In addition, when the mucosa was exposed to capsaicin repeatedly, this response showed a marked tachyphylaxis at a high concentration (6 mg/ml). These results suggest that intragastric capsaicin increased GMBF selectively through capsaicin-sensitive sensory neurons, and this action may involve endogenous prostaglandins.

Cardiorespiratory Responses to Inhaled Laryngeal Irritants

AbstractNumerous protective and defensive reflexes are elicited from the upper airway, but the extent to which receptors with myelinated and nonmyelinated fibers contribute to these reflex responses is not known. In this study we compared the effects of capsaicin (CAPS), a specific C-fiber receptor stimulant, and ammonia (NH3), a nonspecific stimulant, on breathing pattern, heart rate, and blood pressure in anesthetized, spontaneously breathing rats and dogs. Nebulized CAPS and NH3 vapor were added to a constant stream of air passing through the functionally isolated upper airway In the rat both CAPS and NH3 prolonged the expiratory duration TE (p <.05) and increased blood pressure (p <.05) and laryngeal resistance (p < .05). The respiratory and cardiovascular responses to CAPS occurred with a longer (5–7×) delay compared to NH3 and were markedly reduced or abolished by superior laryngeal nerve section (SLN). In contrast, in the dog CAPS did not alter any of the parameters monitored, and NH3 inhalation pr...

Effects of capsaicin in rat and pigeon on peripheral nerves containing substance P and calcitonin gene-related peptide

Substance P and calcitonin gene-related peptide were immunohistochemically identified in axons innervating the cornea and the ureter of adult rats and pigeons. The two neuropeptides were similarly distributed in both species. Capsaicin pretreatment induced depletion of the immunoreactivity; this was quantitatively and qualitatively different in rats and pigeons. Topical application of capsaicin (1%) reduced the immunoreactivity in the cornea in both species by 50%. Systemic capsaicin treatment completely depleted both peptides from the corneal innervation of rats but reduced the peptide content only by 50% in the cornea of pigeons. In the ureter of rats, capsaicin pretreatment completely depleted the peptide immunoreactivity. In pigeons the peptide depletion was only complete in the outer longitudinal muscle layer. Whereas only a few immunoreactive fibres were observed in the circular muscle layer, about 50% of the peptide remained in the inner longitudinal muscle layer. The results demonstrate that peptidergic afferents in the cornea and ureter of pigeons are sensitive to capsaicin, although birds do not show nociceptive responses to local administration of the drug. The long-term depletion of substance P and calcitonin gene-related peptide by capsaicin is discussed with regard to the possibility that functionally capsaicin receptors may exist in the axon but not at nerve endings.

A new model for inflammatory colonic disease induced by capsaicin in rats.

A new model for inflammatory colonic disease induced by capsaicin in rats.

Adrenal sympathetic efferent nerve and catecholamine secretion excitation caused by capsaicin in rats.

Capsaicin enhances adrenal medullary catecholamine secretion. The participation of the central nervous system on this enhancement by capsaicin was investigated in alpha-chloralose-urethan- or halothane-anesthetized rats. Intravenous administration of capsaicin caused a rapid and marked increase in adrenal sympathetic nerve activity. The nerve activity began to show an increase with the administration of capsaicin at a dosage of 20 micrograms/kg and significantly increased with a dosage of 200 micrograms/kg, i.e., capsaicin was found to cause a dose-dependent increase in adrenal nerve activity. Cholinergic blocking with hexamethonium bromide and atropine sulfate (1 and 5 mg/kg iv, respectively) attenuated the adrenal epinephrine secretion caused by capsaicin. The direct action of capsaicin on adrenal catecholamine secretion was examined using a retrograde perfusion system of left adrenal gland. Up to 8.2 X 10(-5) M capsaicin did not enhance catecholamine secretion from the adrenal gland. These results suggest that the enhancement of physiological catecholamine secretion by capsaicin is mainly through activation of the central nervous system.

Selective excitation by capsaicin of mechano-heat sensitive nociceptors in rat skin

The effect of close-by arterial injections of capsaicin on single afferent fibers of the saphenous nerve was studied on 82 units from control rats and on 44 units from rats pretreated with capsaicin (total dose 200 mg/kg applied subcutaneously under anesthesia 3 days before the experiment). In control rats low doses of capsaicin selectively excited mechano-heat sensitive cutaneous nociceptors (polymodal C fiber nociceptors and MH-Aδ nociceptors). The median threshold dose for polymodal nociceptors was 0.1 μg. Repeated injections of capsaicin in near-threshold doses evoked reproducible effects without obvious signs of desensitization. In contrast Aδ high-threshold mechanoreceptors, hair follicle receptors, cold receptors and C fiber mechanoreceptors were not excited by capsaicin even at doses of 5 μg. These high doses activated, however, some SA-II mechanoreceptors after a time lag, probably due to increased tissue turgor induced by plasma extravasation. Systemic capsaicin pretreatment of adult rats resulted in a selective decrease in the proportion of polymodal nociceptors among the afferent C-units, and an increment in the threshold dose of capsaicin of the responding polymodal nociceptors. It is concluded that in the adult rat capsaicin exerts a selective stimulatory and blocking effect on cutaneous mechano-heat sensitive nociceptors conducting both in the C fiber and Aδ fiber range.

Formation and metabolism of the pungent principle of Capsicum fruits. Part XVIII Enhancement by capsaicin of energy metabolism in rats through secretion of catecholamine from adrenal medulla.

Capsaicin (CAP), a pungent principle of hot red pepper, enhances energy metabolism in rats fed a high fat diet. In this study, the site of action of CAP in rats was investigated in vivo with the serum glucose level as an index of energy metabolism. Administration of CAP (4 mg/kg, ip) caused a significant increase in the serum glucose level. Treatment with hexamethonium bromide (5 mg/kg, ip) and atropine sulfate (1 mg/kg, ip) did not affect the serum glucose response to CAP. Rats treated with 6-hydroxydopamine hydro bromide (30 mg/kg, ip) or reserpinie (5 mg/kg/day for 5 days) also responded to CAP. Adrenodemedullation, however, completely prevented the response to CAP, and injection of epinephrine into the adrenodemedullated rats significantly increased the serum glucose level. These results suggest that the CAP-induced enhancement of the energy metabolism in rats occurs via the secretion of catecholamine from the adrenal medulla.

Action of intrathecal capsaicin and its structural analogues on the content and release of spinal substance P: Selectivity of action and relationship to analgesia

Intrathecal injections of capsaicin (CAP) and 4 other homovanillic acid (HMV) derivatives related to the structure of CAP were carried out. Capsaicin, 1-nonenoylvanillylamide (NVA), HMV-dodecylamide (DCA) (but not HMV-cyclohexylamide (CHA) or HMV-hexadecylamide (HDC)) reduced the spinal content of substance P (SP), as measured by radioimmunoassay (RIA), and increased the tail-flick latency. Similar injection of kainic acid and piperine reduced levels of SP but failed to affect the tail-flick latency. None of the agents used affected spinal levels of cholecystokinin (CCK) or vasoactive intestinal peptide (VIP) as measured by RIA. In experiments using in vivo superfusion of the rat spinal cord, CAP, DCA and NVA were found to stimulate release of SP. Capsaicin had no effect on the levels of CCK or VIP immunoreactivity in the spinal superfusate. A tachyphylaxis to the effect of CAP and DCA on spinal SP release was demonstrated. Pretreatment with either agent blocked the releasing effect of the second. Pretreatment with an inactive analogue (HDC) had no effect on the subsequent activity of CAP. Kainic acid and piperine did not induce release of SP from the spinal cord. The relative selectivity of spinally administered capsaicinoids with regard to their effects on the content and release of peptides known to be contained in primary afferents and the presence of a similar structure-activity relationship for depletion and release of SP, desentization and antinociception suggest the presence of a specific receptor site associated with a specific population of primary afferents through which pain information may pass. Whether SP is an ‘afferent pain transmitter’ is not clear, but at the least, it appears to serve as a marker for a population of afferents acted upon by spinally administered capsaicinoids.

Tetrodotoxin-resistant sodium and calcium components of action potentials in dorsal root ganglion cells of the adult mouse.

Tetrodotoxin-resistant sodium and calcium components of action potentials in dorsal root ganglion cells of the adult mouse.

Stimulation and desensitization of the hypothalamic heat-sensitive structures by capsaicin in rats.

1. In rats the injection of capsaicin into the pre-optic area of the anterior hypothalamus produces a prompt fall in body temperature and abolishes shivering. With repeated injections of capsaicin the hypothermic effect gradually diminishes and finally vanishes (local desensitization).2. Rats desensitized by hypothalamic injections exhibit a behaviour similar to rats pre-treated parenterally with capsaicin: put in a heat box at 37-39 degrees C they lose their ability to regulate against overheating of their bodies and respond with an enhanced hyperthermia to strong sensory stimuli such as repeated pinching of the tail.3. Parenteral desensitization strongly inhibits the effect of capsaicin given into the hypothalamus. On the other hand in intrahypothalamically desensitized rats the hypothermic response to subcutaneously given capsaicin is also reduced.4. The hypothermic response to local heating of the anterior hypothalamus by diathermy (from 1 to 4 degrees C above the initial temperature) was markedly reduced or even abolished in rats pre-treated parenterally with large doses of capsaicin.5. It is concluded that the hypothalamic warmth detectors are stimulated and subsequently desensitized by capsaicin. Thus, in the thermoregulatory disturbances caused by capsaicin the impairment of the hypothalamic warmth detectors plays an important role.6. Capsaicin is proposed as a tool in studying the function of the hypothalamic warmth detectors.