Nitric oxide mediates capsaicin-induced increase in cochlear blood flow

Capsaicin has been previously shown to increase cochlear blood flow (CBF) in a dose-dependent manner. The aim of this study was to define the role of nitric oxide (NO) in capsaicin-induced changes in CBF. This was investigated in the anesthetized guinea pig, utilizing laser Doppler flowmetry. Application of capsaicin (64.8 and 6.48 nmol in 2 μl of saline) to the round window membrane (RWM) caused increases in CBF (34 ± 2.8% of baseline (BL) and 28 ± 2.3% BL, respectively (P < 0.001)). Application of the NO synthase inhibitor, N^G-nitro-l-arginine methyl ester (l-NAME) (10 mg/kg intravenously or topically to the RWM) reduced blood flow in the cochlea, as previously reported. After pretreatment with i.v. l-NAME, the effect of capsaicin on CBF was significantly decreased. With the dose of capsaicin at 64.8 nmol, the increase in CBF fell from 34 ± 2.8% BL to 6.9 ± 1.5% BL (P < 0.001), and at 6.48 nmol it fell from 28 ± 2.3% BL to 4.8 ± 1.6% BL (P < 0.001). RWM l-NAME application also decreased the capsaicin vasodilatation effect. A capsaicin dose of 64.8 nmol resulted in only a 10 ± 2.5% BL increase in CBF, and with 6.48 nmol capsaicin the increase was 7.8 ± 2.2% of BL (P < 0.001). Capsaicin-sensitive sensory neurons in other systems are generally known to release substance P (SP), which in turn elicits release of endothelium derived relaxing factor (NO). The results of this study indicate that NO is a mediator of capsaicin-sensitive sensory neuronal function in CBF regulation.     

Distribution of substance P in the rat gastrointestinal tract — Lack of effect of capsaicin pretreatment

A new method for extraction of immunoreactive substance P (I-SP) from rat intestine including pulverization of tissue frozen in liquid nitrogen and extraction with acid acetone is described. Using this method, amounts of I-SP in the rat intestine were found to be higher than previously reported. The highest concentrations of I-SP were found in the small intestine. Capsaicin pretreatment of newborn or adult rats had no effect on intestinal I-SP concentrations indicating that intrinsic SP neurones are capsaicin-insensitive.     

Changes in features of degenerating primary sensory neurons with time after capsaicin treatment

Summary Capsaicin (50 mg/kg) was injected into new born mice and 5 and 12 h, and 1, 2, 3, and 5 days later, their lumbar dorsal root ganglia (DRG) with the nerve roots were fixed by immersion. The morphological changes which ensued with time after treatment were examined by light and electron microscopy. The findings were as follows: (a) rapid degeneration of certain smaller B-type neurons, indicating their prompt death, was seen 5 h after treatment. Later, accumulated neurofilaments appeared in larger B-type neurons. Fissures of the cytoplasm and cell fragmentation were also observed as particular features of degeneration. Finally, these degenerating neurons, destined to die, appeared as small round figures with a disorganized nucleus. Severely degenerated neurons were seen throughout the survival time after treatment, but seemed to be most numerous after 2–3 days. (b) Three days after treatment the Nissl substances of large A-type neurons appeared dispersed, forming ring-like bundles in the periphery of cells. Cytoplasmic rupture and large membrane-bound spaces with fine granular or fibrillar materials, indicating peripheral cytolysis, were also conspicuous. Some of these cells showed severe degeneration clearly leading to cell death. The A-type neurons began to degenerate later than the B-type neurons. (c) Satellite cells showed an increased amount of electron-opaque cytoplasm that contained large vacuoles and neuronal cell debris. Mitotic figures were increased in satellite cells 3 days after treatment. (d) Unmyelinated axons in the dorsal root of mice treated with capsaicin became enlarged with accumulation of neurofilaments, synaptic vesicles or various kinds of vesicles, multivesicular bodies amd mitochondria. Numerous dense lamellar bodies appeared in the unmyelinated axons within DRG 3 days after treatment, but were scarcely seen in the dorsal roots. Degeneration of the myelinated fibers increased with time. Interestingly, capsaicin seemed to have both a direct and indirect action on DRG neurons: its direct action induced rapid degeneration of the smaller neurons, whereas its indirect action induced relatively slow degeneration of the larger neurons, causing chromatolytic changes similar to those induced by periphal nerve axotomy. The injury to DRG neurons due to the indirect action seemed to be induced retrogradely.     

Corticotropin-releasing factor and systemic capsaicin-sensitive afferents are involved in abdominal surgery-induced Fos expression in the paraventricular nucleus of the hypothalamus

We previously reported that abdominal surgery induces Fos expression in specific hypothalamic and medullary nuclei and also causes gastric stasis. The gastric ileus is reduced by systemic capsaicin and abolished by central injection of corticotropin-releasing factor (CRF) antagonist. We studied the influence of systemic capsaicin and intracerebroventricular (i.c.v.) injection of the CRF antagonist, α-helical CRF_9–41, on Fos expression in the brain 1 h after abdominal surgery in conscious rats using immunocytochemical detection. In control groups (vehicle s.c. or i.c.v.), abdominal surgery (laparotomy with cecal manipulation) performed under 7–8 min of enflurane anesthesia induced Fos staining in neurons of the spinal trigeminal, C1/A1 group, ventrolateral medulla, central amygdala, parabrachial nucleus, cuneate nucleus, nucleus tractus solitarii (NTS), paraventricular nucleus of the hypothalamus (PVN) and supraoptic nucleus (SON). Capsaicin (125 mg/kg s.c., 2 weeks before) or α-helical CRF_9–41 (50 μg i.c.v., before surgery) reduced the number of Fos-positive cells by 50% in the PVN while not modifying the number of Fos-labelled cells in the other nuclei. These results indicate that capsaicin-sensitive primary afferents and brain CRF receptors are part of the pathways and biochemical coding through which abdominal surgery activates PVN neurons 1 h post surgery.     

Capsaicin-sensitive afferents in the rat urinary bladder activate a spinal sympathetic cardiovascular reflex

Summary In urethane-anesthetized rats with an intact spinal cord, application of capsaicin on the outer surface of the urinary bladder produced a transient bradycardia, hypotension and negative cardiac inotropism which were neither prevented by i. v. atropine (0.5 mg/kg) nor by cervical vagotomy. In acute spinal rats (C2-C3) application of capsaicin (0.2 and 2 pg in 25 pl) on the urinary bladder induced a transient hypertension, tachycardia and positive cardiac inotropism. A second application (30 min later) induced minor cardiovascular effects, expecially with the higher dose, indicating desensitization. All cardiovascular responses to topical capsaicin were abolished by systemic capsaicin desensitization (50 mg/kg s. c., 4 days before). The excitatory cardiovascular response to capsaicin in acute spinal rats was markedly reduced by bilateral section of pelvic but not hypogastric nerves. Further, it was abolished by pretreatment with hexamethonium (20 mg/kg i.v.) or reserpine (5 mg/kg i. p., 2 days before) and reduced, at various extent for the different components, by phentolamine (0.5 mg/kg i. v.) or propranolol (1 mg/kg). In rats with pelvic and hypogastric nerves intact, section of the cord at a level (T12-L1), just above the medullary segments which receive primary afferent input from the bladder (L6-S1), abolished the excitatory cardiovascular response to application of capsaicin on the bladder. In spinal rats (C2-C3) rapid distension of the urinary bladder with saline produced transient tachycardia, hypertension and positive cardiac inotropism similar to that evoked by capsaicin. These responses were not observed in rats systemically pretreated with capsaicin. These findings indicate that certain bladder afferents which are susceptible to capsaicin desensitization in adult rats activate a spinal reflex having excitatory influence on cardiovascular function. This response is apparently mediated by spinal centers located above the site of entry of bladder pelvic afferents into the cord and most likely involves excitation of preganglionic sympathetic neurons in the spinal cord.Send offprint requests to S. Giuliani at the above address     

A study of the atropine-resistant component of the neurogenic response of the rabbit urinary bladder

Rabbit bladder body was stimulated to contract by a number of agonists, of which bradykinin was the most potent, and ATP one of the least potent substances tested. The atropine-resistant component of the neurogenic response was unaffected by 2 X 10(-5) M chlorpheniramine or 10(-6) M methysergide, doses which suppressed responses to histamine or 5HT. Indomethacin 10(-5) M, or 10(-5) M capsaicin both reduced the atropine-resistant component. Following treatment with 10(-6) M atropine and 10(-5) M prazosin, 10(-4) M ANAPP3 produced a further suppression of the response, but did not antagonize the response to ATP. In the bladder body, the transmitter(s) responsible for the neurogenic response may be acetylcholine and prostaglandins and possibly ATP and substance P.     

Capsaicin inhibits catecholamine secretion and synthesis by blocking Na+ and Ca2+ influx through a vanilloid receptor-independent pathway in bovine adrenal medullary cells

We report here the effects of capsaicin, a flavoring ingredient in the hot pepper Capsicum family, on catecholamine secretion and synthesis in cultured bovine adrenal medullary cells. Capsaicin inhibited catecholamine secretion (IC₅₀=9.5, 11.8, and 62 μM) stimulated by carbachol, an agonist of the nicotinic acetylcholine receptor, by veratridine, an activator of voltage-dependent Na⁺ channels, and by high K⁺, an activator of voltage-dependent Ca²⁺ channels, respectively. Capsaicin also suppressed carbachol-induced ²²Na⁺ influx (IC₅₀=5.0 μM) and ⁴⁵Ca²⁺ influx (IC₅₀=24.4 μM), veratridine-induced ²²Na⁺ influx (IC₅₀=2.4 μM) and ⁴⁵Ca²⁺ influx (IC₅₀=1.1 μM), and high K⁺-induced ⁴⁵Ca²⁺ influx (IC₅₀=5.8 μM). The reduction in catecholamine secretion caused by capsaicin was not overcome by increasing the concentration of carbachol. Furthermore, capsazepine (10 μM), a competitive antagonist for the transient receptor potential vanilloid 1, and ruthenium red (30 μM), a nonselective cation channel antagonist, did not block the inhibition by capsaicin of catecholamine secretion. Capsaicin also suppressed both basal and carbachol-stimulated ¹⁴C-catecholamine synthesis (IC₅₀=10.6 and 26.4 μM, respectively) from [¹⁴C] tyrosine but not from l-3, 4-dihydroxyphenyl [3-¹⁴C] alanine ([¹⁴C] DOPA) as well as tyrosine hydroxylase activity (IC₅₀=8.4 and 39.0 μM, respectively). The present findings suggest that capsaicin inhibits catecholamine secretion and synthesis via suppression of Na⁺ and Ca²⁺ influx through a vanilloid receptor-independent pathway.     

Behavioral and physiological effects of capsaicin in red-winged blackbirds

We injected red-winged blackbirds (Agelaius phoeniceus) subcutaneously with capsaicin, and assessed (a) changes in basal body temperature, (b) ability to discriminate warm from cool drinking water, and (c) sensitivity to oral and topical applications of capsaicin, a trigeminal irritant. As predicted from studies of mammals, the injections seemed to disrupt thermoregulation when the ambient temperature increased, and eliminated discrimination between warm and cool drinking water (Figs. 1 and 2). In contrast to effects on mammals, injections failed to observably diminish oral or topical sensitivity to capsaicin and apparently induced a capsaicin preference in two-bottle drinking tests between capsaicin and its vehicle (Fig. 3). Such preferences were context-dependent, however, since water was reliably preferred to capsaicin or vehicle in three-bottle tests. To our knowledge, the present work is the first to report physiological and behavioral effects of capsaicin on birds, and the first to suggest that the substance may have different behavioral and physiological effects on different classes of animals.     

咳嗽症状严重程度评价

咳嗽是临床上常见的症状,可由许多疾病引起.评价患者咳嗽程度能够帮助了解患者生活质量受影响程度以及评估治疗效果.近年,发展出了许多咳嗽评估方法包括有咳嗽评分,生活质量问卷,咳嗽监测以及咳嗽反射敏感性测定.在临床实际中应综合使用这些方法以互为补充.