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[The effect of anti-NGF and NGF on the responses to noxious heat in mice treated with capsaicin in the neonatal period].

Unexpectedly, despite the profound loss of C-fibers in the dorsal roots of mice injected capsaicin on day 2 of life, they showed normal responses to nociceptive heat. To examine the cause of this conflicting phenomenon, we studied the effect of anti-NGF and NGF on the response to noxious heat in mice pretreated with capsaicin. Capsaicin (50 mg/kg) was injected on the 2nd day of life, and 5 days later, anti-NGF (3 microliters/g) was daily injected for 30 days. Capsaicin was also injected on day 10 of life, and NGF (3 microliters/g) was daily injected for 30 days from 5 days after treatment. From 10 days after capsaicin treatment, the mice were stimulated by radiant heat (Hargreaves' method) every 10 days up to 60 days and every 20 days from 60 to 80 days. The same test was undertaken in age-matched mice. Withdrawal latencies of the mice treated with both capsaicin and anti-NGF were significantly retarded compared with those of the animals treated with only capsaicin. Thus, it was suggested that the treatment of capsaicin on day 2 induces sprouting from the remaining primary sensory neurons. On the other hand, the latencies of the mice treated with both capsaicin and NGF were short compared with those of the animals treated with only capsaicin. The results may be attributed to the reinforcement of the sprouting from remaining neurons. However, we must not neglect the effect of individual treatment with NGF or anti-NGF.

Animals↗

Relationship between self-reported odor intolerance and sensitivity to inhaled capsaicin: proposed definition of airway sensory hyperreactivity and estimation of its prevalence.

STUDY OBJECTIVES: The aim of this study was to investigate the relationship between the behavioral consequences of self-reported odor sensitivity with the chemical sensitivity scale for sensory hyperreactivity (CSS-SHR) and cough sensitivity to inhaled capsaicin. We also wanted to estimate the prevalence of airway sensory hyperreactivity (SHR), which was defined as a positive CSS-SHR score in combination with a positive capsaicin inhalation test result. DESIGN: A general population-based study with randomly selected individuals after stratification for age and gender. SETTING: Skövde Central Hospital, Departments of Lung Medicine and Otorhinolaryngology, Sweden. PARTICIPANTS: A total of 693 randomly selected individuals from a population-based study in which 595 persons (86%) responded to the CSS-SHR questionnaire. INTERVENTIONS: The individuals were divided into four groups with different odor sensitivity according to their CSS-SHR score. Of these, 137 individuals were randomly recruited for the capsaicin inhalation test. Capsaicin inhalation was performed with concentrations of 0.4 and 2.0 mumol/L in a randomized order. The number of coughs were registered and counted for 10 min from the start of each inhalation. MEASUREMENTS AND RESULTS: Of the 137 individuals who were recruited for the capsaicin inhalation test, 103 (75%) participated. Sixteen individuals had increased cough sensitivity and fulfilled the criteria for a positive capsaicin inhalation test result. Of the individuals with a positive capsaicin inhalation test result, > 80% also had a positive CSS-SHR score. Only 5% of the individuals with a negative CSS-SHR score had a positive capsaicin inhalation test result. The order of inhaled capsaicin concentration was found to influence the results. The prevalence of SHR with the definition given above was estimated to be 6.3% in this general population. CONCLUSIONS: A high CSS-SHR score was found to be directly related to the sensitivity for inhaled capsaicin, which made it possible to relate subjective data to objective findings.

Administration, Inhalation↗

Neuroanatomical effects of capsaicin on the primary afferent neurons.

Studies by N. JANCSO and his associates in the 1970's established that capsaicin in paprika exerts selective damage on nociceptive primary sensory neurons. The physiological and pharmacological aspects of capsaicin's effect have been repeatedly reviewed, but no report seems available concerning the neuroanatomical changes caused by capsaicin. This paper first reviews the neuroanatomical aspect of the lesion caused by capsaicin. Special attention is paid to quantitative estimations made by our group and others on the loss of dorsal root ganglion (DRG) cells, dorsal root nerve fibers, the saphenous nerve, chorda tympani nerve, and pulp nerves after neonatal treatment with capsaicin. The degenerating process of DRG cells induced by capsaicin is discussed with respect to necrosis and apoptosis. The capsaicin receptors found recently are concisely introduced with reference to their action. A discrepancy between a marked loss of dorsal root C-fibers and an unexpectedly intact response to noxious heat in mice treated with capsaicin at neonate is discussed, and attension is given to nerves sprouting from capsaicin-resistant DRG cells in the superficial dorsal horn. In addition, the architecture of the synapses between the central endings of the capsaicin-sensitive primary afferent neurons and the intrinsic inhibitory interneurons is described and its possible significance considered in terms of the transmission of nociceptive information.

Animals↗

Capsaicin-induced cell death in a human gastric adenocarcinoma cell line.

AIM: Capsaicin, a pungent ingredient found in red pepper, has long been used in spices, food additives, and drugs. Cell death induced by the binding of capsaicin was examined in a human gastric adenocarcinoma cell line (AGS cells). METHODS: By using XTT-based cytotoxicity assay, flow cytometry using the TUNEL method, and quantitation of DNA fragmentation, both cell death and DNA fragmentation were detected in AGS cells treated with capsaicin. By using Western blotting methods, capsaicin reduced the expression of Bcl-2, the antiapoptotic protein, in AGS cells in a concentration-dependent manner. RESULTS: After incubation of AGS cells with capsaicin for 24 h, cell viability decreased significantly in a dose-dependent manner. After incubation of AGS cells with capsaicin for 24 h, apoptotic bodies also significantly increased, and were again correlated with the dose of capsaicin. When the concentration of capsaicin was 1 mmol/L, the amount of DNA fragments also increased. Similar results were also in the lower traces. CONCLUSION: These results suggest that capsaicin-induced cell death might be via a Bcl-2 sensitive apoptotic pathway. Therefore, capsaicin might induce protection from gastric cancer.

Adenocarcinoma↗

Capsaicin responses in heat-sensitive and heat-insensitive A-fiber nociceptors.

The recently cloned vanilloid receptor (VR1) is postulated to account for heat and capsaicin sensitivity in unmyelinated afferents. We sought to determine whether heat and capsaicin sensitivity also coexist in myelinated nociceptive afferents. Action potential (AP) activity was recorded from single A-fiber nociceptors that innervated the hairy skin in monkey. Before intradermal injection of capsaicin (10 microg/10 microl) into the receptive field, nociceptors were classified as heat-sensitive (threshold, </=53 degrees C, 1 sec) or heat-insensitive afferents and as mechanically sensitive (von Frey threshold, <6 bar) or mechanically insensitive afferents. All heat-sensitive afferents (n = 16) were insensitive to mechanical stimuli but responded to the intradermal injection of capsaicin (69 +/- 7 APs in 10 min). Responsiveness to mechanical stimuli, thermal stimuli, and capsaicin varied in their receptive fields; the majority of receptive field sites (24 of 36) were responsive to only one or two stimulus modalities, whereas only eight sites responded to all three modalities. For most heat-insensitive afferents, the activity induced by the capsaicin injection did not exceed the activity induced by needle insertion alone. However, the largest response to capsaicin (314 +/- 98 APs in 10 min) was observed for five afferents that were insensitive to heat as well as mechanical stimuli and therefore may be classified as cutaneous chemoreceptors. These results suggest that A-fiber nociceptors play a role in the pain and hyperalgesia associated with capsaicin injection. Our finding that a subgroup of capsaicin-sensitive A-fiber nociceptors are insensitive to heat predicts the existence of heat-insensitive capsaicin receptors.

Action Potentials↗

Capsaicin-induced activation of erythrocyte membrane sodium/potassium and calcium adenosine triphosphatases.

Capsaicin is the pungent ingredient present in hot peppers of the genus Capsicum. Capsaicin's effect on sensory neurons has been well studied; however, its effect on non-neuronal cells is still not fully understood. This study was undertaken to evaluate the effect of capsaicin on erythrocyte membrane enzymes: Na+/K(+)-ATPase and Ca(2+)-ATPase. Treatment with capsaicin (0.01-100 microM) caused a transient increase in the activities of both enzymes; the effect declined at lower concentrations of capsaicin, and no significant effect was observed at 0.01 microM capsaicin. The effect of capsaicin was fast with a significant (p<0.01) activation of enzyme activity observed within minutes of incubation. The findings on the effect of capsaicin on human erythrocyte membrane enzymes Na+/K(+)-ATPase and Ca(2+)-ATPase signify the importance of the non-neuronal effects of capsaicin, and the need for evaluating the physiological impact of high capsaicin (capsicum) consumption in some regions of the world.

Benzoates↗

Capsaicin-induced corneal lesions in mice and the effects of chemical sympathectomy.

Effects of chemical sympathectomy on corneal changes induced in mice by a s.c. injection of capsaicin were investigated. Pretreatment with a s.c. injection of 6-hydroxydopamine (6-OHDA) on the 1st and 2nd postnatal day or on the 14th and 15th postnatal day led to a marked suppression of the capsaicin-induced corneal lesions. This suppressive effect also was evident in case of administration after capsaicin treatment. Intraventricular injection of 6-OHDA had a slight, transient effect. DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine], another potent substance used for sympathetic denervation, had a suppressive effect similar to that of 6-OHDA. The concentration of capsaicin in tissues of the head was unaltered with 6-OHDA. The content of substance P (SP) in the ocular anterior segments was decreased, dose-dependently, with capsaicin administration. Neonatal administration of 6-OHDA decreased the rate of capsaicin-induced reduction of SP. However, this effect of 6-OHDA was too slight to explain the suppression of the corneal lesions, as the intensity score of lesions with a large dose of capsaicin after 6-OHDA was lower than that with a small dose of capsaicin without 6-OHDA, whereas SP content in the former was still much lower than that in the latter. On the other hand, the content of norepinephrine in the ocular tissues was decreased in the presence of 6-OHDA but not capsaicin. These results suggest that the corneal changes induced by capsaicin are largely inhibited by a decreased activity in the peripheral sympathetic system.

Animals↗

Involvement of calcitonin gene-related peptide in the positive chronotropic and inotropic effects of piperine and development of cross-tachyphylaxis between piperine and capsaicin in the isolated rat atria.

Piperine as well as capsaicin showed positive chronotropic and inotropic effects in the isolated spontaneously beating right atria and electrically driven left atria of rats, respectively. The responses to piperine were not affected by the presence of the antagonists to norepinephrine, acetylcholine, histamine and serotonin. However, once the tissue was pretreated with piperine or capsaicin, the response to subsequent application of piperine was reduced significantly. Both positive chronotropic and inotropic effects of capsaicin were also attenuated after the tissue was treated with piperine or capsaicin. Thus, not only a tachyphylaxis to either piperine or capsaicin itself but also a cross-tachyphylaxis between piperine and capsaicin developed. Nonadrenergic noncholinergic calcitonin gene-related peptide (CGRP)-like immunoreactive nerves were distributed in the muscle layers of both atria. CGRP-like immunoreactivity was depleted considerably by treatment of the tissue with piperine or capsaicin. When endogenous CGRP was depleted, although the positive chronotropic and inotropic effects of piperine and capsaicin were abolished, the effects of CGRP and isoproterenol were not affected. These results indicate that both piperine and capsaicin cause positive chronotropic and inotropic responses by releasing CGRP from nonadrenergic noncholinergic nerves, and that the development of cross-tachyphylaxis between piperine and capsaicin is due to the depletion of endogenous CGRP.

Alkaloids↗

Effects of topical capsaicin on normal skin and affected dermatomes in herpes zoster.

Hyperalgesia and allodynia, lasting for months or even years, occurs in the form of post-herpetic neuralgia in approximately 70% of adults previously infected with the varicella herpes zoster virus. The present study aimed at testing the analgesic desensitising actions and reversibility of repeated application of topical capsaicin on disordered polymodal nociceptors and peptidergic sensory fibres mediating warm and pain sensation. Cutaneous nociceptor desensitisation was measured using the Glasgow automated thermal threshold test (Medelec TTT). For normal subjects (n = 69) the mean forearm warm threshold was 0.15 +/- 0.07 degrees C and the cold threshold was 0.14 +/- 0.10 degrees C. A variable degree of partial desensitisation of herpes-affected skin was found in 15 patients with post-herpetic neuralgia before capsaicin treatment where the mean threshold elevation for warm detection was 1.19 degrees C and 0.7 degrees C for cold detection, compared with the corresponding normal skin. In preliminary studies of 15 patients with post-herpetic neuralgia, good pain relief averaging 30% or 77% occurred in the affected dermatome(s) after 3 to 4 weeks of 0.01% or 0.05% capsaicin cream respectively, applied 3-4 times daily. The warm thresholds, after chronic capsaicin treatment, increased between 0.1 and 7.60 degrees C, the average elevation being 3.69 degrees C. By contrast cold thresholds after capsaicin altered inconsistently and by only an average of 0.08 degrees C. The results suggest that elevation of the warm threshold may indicate the desensitisation achieved by capsaicin treatment of skin polymodal nociceptors. Cold detection, being dependent upon A-delta cold fibre function, is unaffected by capsaicin treatment. There was a poor correlation between pain relief and elevation of warm detection in response to capsaicin treatment. Generally, it was found that those patients with less initial desensitisation to warm detection as a consequence of post-herpetic neuralgia experienced better pain relief after capsaicin was applied. The method used permits determination of the minimum effective desensitising dose of capsaicin, enables patient compliance and progress to be monitored and should allow the prediction of patients likely to achieve the best response to treatment.

Administration, Topical↗

An antinociceptive effect of capsaicin in the adult mouse mediated by the NH2-terminus of substance P.

Capsaicin in the adult animal is believed to evoke a massive release of substance P (SP) and a subsequent loss of primary afferent C-fiber activity. Given the antinociceptive effect of SP N-terminal metabolites, the present experiments were designed to compare behavioral and nociceptive responses after treatments with capsaicin or the SP NH2-terminal fragment, SP(1-7), and to determine whether they share a common mechanism of action. When adult mice were tested using the hot-plate assay, 24 hr after intrathecal injections of either capsaicin (0.3-2.6 nmol) or SP(1-7) (22.5 pmol-10 nmol), a dose-related antinociception was observed. The caudally directed biting and scratching behaviors induced by 1 nmol of capsaicin injected intrathecally were also greatly reduced 24 hr after either 2.6 nmol of capsaicin or 10 nmol of SP(1-7). Pretreatment with an antagonist of the NH2-terminus of SP, [D-Pro2,D-Phe7]-SP(1-7), prevented the long-term effects of capsaicin and of SP(1-7) on capsaicin-induced behaviors in our paradigm at doses that the COOH-terminal antagonist of neurokinin activity, [D-Pro2,D-Trp7,9]-SP, did not. The antinociceptive effect of capsaicin in the adult animal is, therefore, mimicked by SP(1-7) and attenuated by [D-Pro2,D-Phe7]-SP(1-7), suggesting that the NH2-terminus of SP and its NH2-terminal metabolites, released in response to capsaicin, may contribute to the mediation of capsaicin's antinociceptive effect.

Analgesics↗

Prior optic nerve transection reduces capsaicin-induced degeneration in rat subcortical visual structures.

Capsaicin is a neurotoxin capable of causing degeneration in specific sites throughout the neuraxis, including the suprachiasmatic nucleus (SCh), the ventrolateral geniculate nucleus (VLG), the intergeniculate leaflet (IGL), and the olivary and medial pretectal nuclei (OPT and MPT). In this experiment, we tested the hypothesis that capsaicin-induced terminal degeneration in the SCh, VLG, IGL, OPT, and MPT results from destruction of retinal ganglion cells and their axonal projections to these sites. In the first experiment, silver stains were used to examine degeneration in the retina induced by systemic capsaicin treatment. Capsaicin caused degeneration of ganglion cells, bipolar cells, and nerve terminals in the retina, which could be observed between 2 and 24 hours after treatment. In the second experiment, 15-day-old rat pups were enucleated unilaterally. Five days or 2, 5, or 10 months later, they were injected systemically with capsaicin and killed 6 hours (pups) or 18 hours (adults) later for analysis with a cupric silver stain. In rats of all ages, prior monocular enucleation reduced or eliminated capsaicin-induced degeneration in the contralateral SCh, VLG, IGL, OPT, and MPT. In the third experiment, rat pups were treated systemically with capsaicin or vehicle solution at 12 days of age and given unilateral intravitreal injections of cholera toxin conjugated to horseradish peroxidase (CT-HRP) 3 days prior to sacrifice at 20 days of age. Transport of CT-HRP to the SCh, VLG, IGL, MPT, and OPT was attenuated but not abolished by capsaicin pretreatment. Results suggest that capsaicin causes degeneration in the SCh, VLG, IGL, MPT, and OPT by selective destruction of a subpopulation of retinal ganglion cells with axonal projections to these sites.

Animals↗

Roles of JNK-1 and p38 in selective induction of apoptosis by capsaicin in ras-transformed human breast epithelial cells.

Efforts have been made to develop a chemoprevention strategy that selectively triggers apoptosis in malignant cancer cells. Previous studies showed that capsaicin, the major pungent ingredient of red pepper, had differential effect between normal and transformed cells. As an approach to unveil the molecular mechanism by which capsaicin selectively induces apoptosis in transformed cells, we investigated the effect of capsaicin in nontransformed and ras-transformed cells of a common origin: parental (MCF10A) and H-ras-transformed (H-ras MCF10A) human breast epithelial cells. Here, we show that capsaicin selectively induces apoptosis in H-ras-transformed cells but not in their normal cell counterparts. The capsaicin-induced apoptosis, which is dependent on ras transformation, involves the activity of DEVDase (caspase-3 like). In H-ras MCF10A cells, capsaicin treatment markedly activated c-Jun N-terminal protein kinase (JNK)-1 and p38 matigen-activated protein kinase (MAPK) while it deactivated extracellular signal-regulated protein kinases (ERKs). The use of kinase inhibitors and overexpression of dominant-negative forms of MAPKs demonstrated a role of JNK-1 and p38, but not that of ERKs, in apoptosis induced by capsaicin in H-ras-transformed MCF10A cells. Based on the present study, we propose that capsaicin selectively induces apoptosis through modulation of ras-downstream signaling molecules in ras-activated MCF10A cells. Taken in conjunction with the fact that uncontrolled ras activation is probably the most common genetic defect in human cancer cells, our finding may be critical to the chemopreventive potential of capsaicin and for developing a strategy to induce tumor cell-specific apoptosis.

3T3 Cells↗

Effects of capsaicin on mechanoenergetics of excised cross-circulated canine left ventricle and coronary artery.

Capsaicin selectively acts on sensory nerve endings in cardiac muscles and coronary arterial smooth muscles. Capsaicin at high doses has cell-nonselective effects including both inhibition of cardiac muscle exciteability and enhancement of vascular smooth muscle tone. We studied whether and how intracoronary infusion of capsaicin affects mechanoenergetics of the excised blood-perfused canine heart and coronary vascular resistance. We found that capsaicin at low concentrations increased Emax (a contracility index) and oxygen consumption (VO2) possibly due to a specific action on capsaicin-sensitive sensory nerves in left ventricular muscles, though in a small number of hearts (3/10). This result coincides with the reported histochemical observations that the distribution of capsaicin-sensitive sensory nerves in the canine left ventricle is not dense. Capsaicin at high doses dose-dependently decreased Emax and proportionally decreased coronary flow. It also lowered the linear VO2-PVA (pressure-volume area; total mechanical energy) relationship without a change in the slope, decreasing unloaded VO2 (VO2 intercept of the VO2-PVA relation). These effects of high-dose capsaicin seem to be direct negative inotropic action on cardiac muscles associated with enhancement of coronary arterial smooth muscle tone, since these effects were not desensitized. No morphological changes of myocardial cells or mitochondria were detected. Therefore, the negative inotropic action is not due to the toxic effect of capsaicin.

Animals↗

Capsaicin-sensitive nerves modulate resting blood flow and vascular tone in rat gut.

Acute and chronic treatments with capsaicin were used to evaluate the role of afferent neurons in the regulation of intestinal blood flow. Experiments were performed on anesthetized rats, in which mean intestinal blood flow was determined with a pulsed Doppler flowmeter, mean systemic arterial pressure was determined with a transducer, and intestinal vascular conductance (C) was calculated from these measurements. Acute administration of periarterial capsaicin (0.5 mg) induced biphasic intestinal vascular responses. An early hyperemic response occurred with a maximal increase in blood flow of 31% at 5 min, followed by a decrease in blood flow of 17% at 30 min. Arterial pressure was decreased by the application of capsaicin, initially by 10%. There was an early increase of 49% in conductance, followed by a 15% decrease, compared with control values. When 1 or 4 mg capsaicin was instilled into the lumen of the jejunum there was a response pattern similar to that observed after periarterial application of capsaicin. Intrajejunal capsaicin (4 mg) increased blood flow by 51%, followed by a decrease of 16%. Mean mesenteric artery conductance was increased by 32% initially and subsequently was decreased by 21%, in response to acute intrajejunal administration of capsaicin. Both mean blood flow and conductance were increased (44% and 76%, respectively) in adult rats chronically pretreated with capsaicin (170 mg total dose) when compared with vehicle-treated controls. However, in rats pretreated neonatally with capsaicin (50 mg/kg) and allowed to mature, basal flood flow was lower than in control animals but C was not different from control littermates.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Actions of calcitonin gene-related peptide and tachykinins in relation to the contractile effects of capsaicin in the guinea-pig and rat heart in vitro.

1. The effects of calcitonin gene-related peptide (CGRP), neurokinin A (NKA), neuropeptide K (NPK) and substance P (SP) on contractility of the guinea-pig and rat heart were studied in vitro in relation to the response to capsaicin. 2. Human (h) CGRP alpha (alpha) and beta (beta) were equipotent in stimulating the contractile force and rate of the spontaneously beating guinea-pig right atrium. 3. Both NKA and NPK inhibited contractile force and rate in the guinea-pig atrium whilst a mainly negative chronotropic effect was observed in the whole heart. SP did not influence cardiac contractility. 4. Human CGRP alpha and beta mimicked the contractile effects of capsaicin in the guinea-pig atrium. In the whole heart preparation, hCGRP alpha and capsaicin increased heart rate whereas capsaicin also evoked an atropine-resistant inhibition of contractile force. The stimulatory effect of capsaicin on heart rate was absent after systemic capsaicin pretreatment, while the inhibition of ventricular contractile tension remained unchanged. 5. Extended incubation with hCGRP alpha or beta was associated with development of cross-tachyphylaxis between these two agents in the guinea-pig atrium. However, CGRP tachyphylaxis did not change the atrial response to noradrenaline, forskolin or NKA. The stimulatory effects of capsaicin on atrial contractility were absent after tachyphylaxis to hCGRP alpha or beta. 6. There was no detectable supersensitivity to the stimulatory effects of rat (r) CGRP alpha on the spontaneously beating atrium after capsaicin pretreatment of adult or neonatal rats. In conclusion the present data provide further evidence that the capsaicin-induced stimulation of atrial contractility is due to local release of CGRP.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

Analysis of the effects of intravenously injected capsaicin in the rat.

1. I.v. injection of 1 or 3 micrograms capsaicin led to a triphasic blood pressure response in Sprague-Dawley rats but, in contrast to Wistar rats, did not affect heart rate and respiration. The blood pressure response was a sequence of fall (A), return to normal levels or slight rise (B), and fall (C) in blood pressure. The blood pressure response to capsaicin remained unchanged after treatment with adrenoceptor or cholinoceptor antagonists. 2. The initial fall in blood pressure (A) was absent after bilateral vagotomy and in the pithed rat. The delayed fall in blood pressure (C) remained unchanged after vagotomy, but was absent after neonatal capsaicin pretreatment and in the pithed rat. Effect B was not diminished after vagotomy or despinalization: it was augmented in rats treated neonatally with capsaicin. 3. I.a. injection of capsaicin into the hind leg caused a reflex fall in blood pressure which was changed to a reflex rise in rats treated with capsaicin as neonates. 4. The initial and the delayed fall in blood pressure after i.v. injection of capsaicin seems to be reflex responses to stimulation of capsaicin-sensitive small diameter afferent fibres. The intermediate rise in blood pressure appears to result mainly from a direct short vasoconstriction by capsaicin.

Animals↗

The effects of neonatal capsaicin treatment on growth and subsequent reproductive function in the rat.

The results of the present study describe the following effects of neonatal capsaicin treatment on growth and reproductive function in the rat. Neonatal capsaicin treatment in the rat resulted in a retardation of body growth through adulthood most pronounced at 35 days of age. Capsaicin-treated rats had normal estrous cycles, but mated significantly less frequently than age-matched controls. Confirmed matings in capsaicin-treated female rats resulted in significantly fewer pregnancies compared to controls. Male rats treated with capsaicin as neonates produced significantly fewer pregnancies when mated with untreated females compared to controls. Ovulation, sperm transport, and fertilization occur normally in capsaicin-treated rats. The decidual response was markedly diminished in mated capsaicin-treated rats. These findings led to the conclusion that the neurohormonal reflex, which is normally initiated through the stimulation of the cervix by copulation, and which ultimately stimulates secretion of pituitary luteotropic hormones, did not occur in capsaicin-treated rats. Thus, ovarian progesterone secretion was not facilitated resulting in inadequate hormonal support for implantation, pregnancy or pseudo-pregnancy. These data further suggest that the sensory limb of this neurohormonal reflex may consist of capsaicin-sensitive, possibly substance P containing, primary afferent fibers.

Animals↗

Effects of capsaicin on vascular smooth muscle.

Acute administration of capsaicin in vitro produced either vascular smooth muscle contraction (cat middle cerebral artery) or smooth muscle relaxation (guinea pig carotid artery and thoracic aorta). Prior in vivo treatment with capsaicin abolished the relaxation response of guinea pig vessels to acute capsaicin. Instead a contractile response was seen after chronic capsaicin treatment, suggesting that the relaxation response produced by capsaicin is due to release of a vasodilator substance. Substance P caused relaxation in both cat cerebral arteries and the guinea pig thoracic aorta, an effect which was abolished or reduced by endothelial damage. However, responses to acute capsaicin were not altered by endothelial damage, suggesting that substance P does not mediate the relaxation response to acute capsaicin administration. Exposure to capsaicin in vitro did not affect the neurogenic vasodilator response of cat cerebral arteries and did not alter substance P levels. Therefore, it was concluded that the acute effect of capsaicin is composed of two components. A contractile response is most likely due to direct effects on vascular smooth muscle, while a relaxation response is attributed to release of an as yet unidentified bioactive substance distinct from substance P.

Acetylcholine↗