Capsaicin-sensitive Afferent Fibers Research Articles

Daikenchuto, a Traditional Kampo Medicine, Facilitates Mucosal Hyperemic Responses through Activation of TRPA1- and TRPV1-Expressing Sensory Nerves in Rat Stomach

AbstractDaikenchuto is a traditional Kampo medicine used to treat cold sensations and dysmotility in the abdomen. This study investigated the roles of transient receptor potential ankyrin 1- and transient reporter potential vanilloid 1-expressing sensory nerves in daikenchuto-induced gastric mucosal blood flow by pharmacological and immunohistochemical analyses using male Sprague-Dawley rats. Gastric mucosal blood flow was measured in ex vivo stomachs using a laser Doppler flowmeter. Transient receptor potential ankyrin 1 activator allyl isothiocyanate or transient reporter potential vanilloid 1 activator capsaicin were applied for 10 min, and daikenchuto was applied for 10 or 30 min to the rat stomach. Transient reporter potential vanilloid 1 blocker N-(4-t-butylphenyl)-4-(3-chlopyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide and transient receptor potential ankyrin 1 blocker A-967079 were also administered intragastrically. Capsaicin and allyl isothiocyanate increased gastric mucosal blood flow immediately after the intragastric application, which was almost completely inhibited by N-(4-t-butylphenyl)-4-(3-chlopyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide and A-967079, respectively. Daikenchuto increased gastric mucosal blood flow in a concentration-dependent manner. A-967079 significantly inhibited the increase in gastric mucosal blood flow induced by daikenchuto. In contrast, N-(4-t-butylphenyl)-4-(3-chlopyridin-2-yl) tetrahydropyrazine-1(2H)-carboxamide inhibited the responses to daikenchuto only in the late phase but not in the initial phase. Interestingly, in the deafferentation of capsaicin-sensitive sensory fiber in rats, the increased gastric mucosal blood flow induced by daikenchuto was only decreased in the late phase. Although transient receptor potential ankyrin 1- and transient reporter potential vanilloid 1-immunoreactive fibers were observed around the submucosal blood vessels of normal subjects, they were completely absent in the deafferentation of capsaicin-sensitive sensory fibers. Thus, daikenchuto increases gastric mucosal blood flow via transient receptor potential ankyrin 1- and transient reporter potential vanilloid 1-co-expressing sensory nerves in rat stomachs.

Effects of dipyrone on the digestive tract.

Dipyrone (metamizole), acting through its main metabolites 4-methyl-amino-antipyrine and 4-amino-antipyrine, has established analgesic, antipyretic, and spasmolytic pharmacological effects, which are mediated by poorly known mechanisms. In rats, intravenously administered dipyrone delays gastric emptying (GE) of liquids with the participation of capsaicin-sensitive afferent fibers. This effect seems to be mediated by norepinephrine originating from the sympathetic nervous system but not from the superior celiac-mesenteric ganglion complex, which activates β2-adrenoceptors. In rats, in contrast to nonselective non-hormonal anti-inflammatory drugs, dipyrone protects the gastric mucosa attenuating the development of gastric ulcers induced by a number of agents. Clinically, it has been demonstrated that dipyrone is effective in the control of colic-like abdominal pain originating from the biliary and intestinal tracts. Since studies in humans and animals have demonstrated the presence of β2-adrenoceptors in biliary tract smooth muscle and β2-adrenoceptor activation has been shown to occur in dipyrone-induced delayed GE, it is likely that this kind of receptors may participate in the reduction of smooth muscle spasm of the sphincter of Oddi induced by dipyrone. There is no evidence that dipyrone may interfere with small bowel and colon motility, and the clinical results of its therapeutic use in intestinal colic appear to be due to its analgesic effect.

Inhibitory effect of luminal saccharides on glucose absorption from an adjacent jejunal site in rats: a newly described intestinal neural reflex.

Nutrients in the lumen of the small intestine are sensed by special cells in the epithelial lining. The ensuing neurohumoral reflexes affect gastrointestinal absorption/secretion, motility, and vascular perfusion. To study in vivo the effect of a monosaccharide (glucose) or polysaccharide (starch) present in the jejunum on glucose absorption from an adjacent part of the intestine and investigate the possible underlying mechanisms. Using the single pass intraluminal perfusion technique, a segment of jejunum (perfusion segment) was continuously perfused with 20mM glucose to determine glucose absorption. One hour later, a bolus of a saccharide was instilled in an isolated adjacent jejunal segment and the change in glucose absorption was monitored for a further 2h. The contribution of neural mechanisms in this process was investigated. Instillation of glucose (20mM or 40mM) in either distal or proximal jejunal pouch elicited immediate and sustained inhibition of glucose absorption (a decrease by 25%; P < 0.01) from the perfused jejunal segment. Comparable inhibition was obtained with instillation of other monosaccharides or starch in the jejunal pouch. This inhibition was abolished by adding tetrodotoxin to the pouch or to the perfused jejunal segment and also by pretreatment with sympathetic blockers (guanethidine or hexamethonium) and by chemical ablation of capsaicin-sensitive primary afferent fibers. Glucose absorption within the jejunum is auto-regulated through backward and forward mechanisms. This regulation is mediated by neural reflexes involving capsaicin-sensitive afferent and sympathetic efferent fibers. These reflexes might serve to protect against hyperglycemia.

Hydrogen peroxide preferentially activates capsaicin-sensitive high threshold afferents via TRPA1 channels in the guinea pig bladder.

There is increasing evidence suggesting that ROS play a major pathological role in bladder dysfunction induced by bladder inflammation and/or obstruction. The aim of this study was to determine the effect of H2 O2 on different types of bladder afferents and its mechanism of action on sensory neurons in the guinea pig bladder. 'Close-to-target' single unit extracellular recordings were made from fine branches of pelvic nerves entering the guinea pig bladder, in flat sheet preparations, in vitro. H2 O2 (300-1000μM) preferentially and potently activated capsaicin-sensitive high threshold afferents but not low threshold stretch-sensitive afferents, which were only activated by significantly higher concentrations of hydrogen peroxide. The TRPV1 channel agonist, capsaicin, excited 86% of high threshold afferents. The TRPA1 channel agonist, allyl isothiocyanate and the TRPM8 channel agonist, icilin activated 72% and 47% of capsaicin-sensitive high threshold afferents respectively. The TRPA1 channel antagonist, HC-030031, but not the TRPV1 channel antagonist, capsazepine or the TRPM8 channel antagonist, N-(2-aminoethyl)-N-[[3-methoxy-4-(phenylmethoxy)phenyl]methyl]thiophene-2-carboxamide, significantly inhibited the H2 O2 -induced activation of high threshold afferents. Dimethylthiourea and deferoxamine did not significantly change the effect of H2 O2 on high threshold afferents. The findings show that H2 O2 , in the concentration range detected in inflammation or reperfusion after ischaemia, evoked long-lasting activation of the majority of capsaicin-sensitive high threshold afferents, but not low threshold stretch-sensitive afferents. The data suggest that the TRPA1 channels located on these capsaicin-sensitive afferent fibres are probable targets of ROS released during oxidative stress.

Selective Inhibitory Effect of Imidafenacin and 5-Hydroxymethyl Tolterodine on Capsaicin Sensitive C Fibers of the Primary Bladder Mechanosensitive Afferent Nerves in the Rat

Imidafenacin and fesoterodine are used to treat overactive bladder. Imidafenacin, fesoterodine and its active metabolite 5-hydroxymethyl tolterodine are muscarinic receptor antagonists. It is believed that these agents act on afferent nerves in addition to smooth muscle. We investigated the effects of imidafenacin and 5-hydroxymethyl tolterodine on single unit afferent activity of mechanosensitive capsaicin sensitive and insensitive primary bladder afferent nerve fibers in rats. Female Sprague Dawley® rats were anesthetized. Single unit afferent activity was recorded from the L6 dorsal roots and classified by conduction velocity as that of Aδ or C fibers. After measuring control single afferent activity during constant filling cystometry the procedure was repeated with intravenous administration of imidafenacin (0.3 to 30 μg/kg) or 5-hydroxymethyl tolterodine (0.01 to 1 mg/kg) at cumulative doses with or without intravesical capsaicin or oxotremorine-M instillation. A total of 139 single unit afferent fibers were isolated from 111 rats, including 19 Aδ and 120 C fibers. Neither imidafenacin nor 5-hydroxymethyl tolterodine significantly affected the overall single unit afferent activity of Aδ or C fibers. Based on capsaicin sensitivity C fibers were divided into capsaicin sensitive and insensitive groups. Each antimuscarinic inhibited the single unit afferent activity of capsaicin sensitive C fibers but not of capsaicin insensitive C fibers at the highest dose. Moreover, oxotremorine-M facilitated single unit afferent activity in a proportion of C fibers. The facilitated single unit afferent activity was significantly attenuated by the highest dose of imidafenacin. These findings demonstrate that imidafenacin and 5-hydroxymethyl tolterodine can selectively inhibit capsaicin sensitive C fibers among mechanosensitive bladder afferents by antagonizing bladder muscarinic receptors.

Orally Given Capsaicinoids do not Modify the Absorption, Metabolism, and Excretion of Aspirin and its Platelet Aggregation in Human Male Healthy Subjects (Human Clinical Pharmacological Phase. I. Examinations)

Backgrounds : 1. The acetylsalicylic acid (ASA, Aspirin) is very frequently used in the every day medical practice as platelet aggregation, analgetic, antipyretic agent in patients with myocardial infarction, prevention of stroke, different thrombophylic events and in different groups of patients and healthy subjects, however, it produces frequently serious gastrointestinal mucosal damage (bleeding, ulceration and perforation); 2. The gastrointestinal mucosal protection was proved by capsaicin(oids), when it (those) was (were) orally given in the doses, which are able to stimulate the capsaicin-sensitive afferent nerve fibers in animal experiments and human observations. Aims of this study were: 1. To evaluate the different pharmacokinetic parameters of capsaicin(oids) (given in doses in stimulatory doses of capsaicin-sensitive afferent nerves) in healthy male volunteers; 2. To study the action of capsaicin(oids) on the co-administration of ASA pharmacokinetic parameters and some pharmacological effect of ASA on the epinephrine-induced platelet aggregation, and 3. To follow strictly the internationally and the human clinical pharmacologically accepted pathway of the pharmaceutical production of a new drug combination [ASA + capsaicin(oids)] for the human medical therapy. Materials and Methods . 1. Fifteen human healthy male subjects were included into this human classical clinical pharmacological phase I., 2. The observations were carried out according to the “Protocol of Study” (protocol number: 1.4.1; EudraCT number: 2000-007048-32), which was permitted by the Hungarian Institute of Pharmacy (dated by June 4, 2009) and by the Hungarian Ethics of Committee for Clinical Pharmacology, Hungarian Medical Research Council (dated by March 1, 2009); 3. The criteria of inclusion and exclusion of healthy male subjects for this study were very strictly identified, 4. The screening and collection of the healthy males were maximally 2 weeks before the starting of study. 5. The phase I. examination covers 5 different sequences (7 days in each), and one week was the post study period, 6. The time-table of examinations (including a short hospitalization time, 3 days for washout, post-study examinations, food and fluid intakes, etc.) were determined, 7. The schedule of the administration of drugs [ASA alone, ASA + capsaicin(oids) – given orally in doses of 400 and 800µg, or placebo] was fixed by the protocol, 8. The human healthy male subjects were randomly treated, 9. The blood samples were obtained from the brachial vena (pre-dose, 0.10, 0.20, 0.40 1.00, 1.30, 2, 4, 6, 10, 12, 16 and 24 hours post dose), 10. The capsaicin and dihydrocapsaicin measured by HPLC, ASA and salicylic acid by HPLC from the plasma of healthy volunteers (during the first 24 hours period) and 11. The effects of capsaicinoids alone, ASA alone, and their combinations were studied on the epinephrine-induced platelet aggregation, 12. Different pharmacokinetic parameters ( C max , T max , AUC 0-tlast , AUC 0- ∞ , mean residence time, MRT ) of ASA and salicylic acid were calculated and these results and were compared in treated groups [ASA alone vs . ASA plus capsaicin(oids) 400 µg vs . ASA plus capsaicin(oids) 800 µg], 12. The extents of platelet aggregation produced by ASA alone and in different combination with capsaicin(oids) on the epinephrine-induced platelet aggregation. Results : 1. The healthy male volunteers tolerated well the different drug candidate combinations, and their applications were safe, 2. Neither capsaicin nor dihydrocapsaicin could be detected in any samples of plasma volunteers after oral application of capsaicin(oids) (given orally in doses of 400 µg and 800 µg) in time period of 0 to 24 hours; 3. The pharmacokinetic parameters of ASA and salicylic acid did not differ in groups treated with ASA alone vs . ASA plus 400 µg capsaicin(oids) vs . ASA plus 800 µg capsaicin(oids), 4. The capsaicin(oids) does (do) not modify the epinephrine-induced platelet aggregation induced by ASA, meanwhile the different doses of capsaicin(oids) alone have no direct effect of the epinephrine-induce platelet aggregation. Conclusions : 1. The capsaicin(oids) acts(act) locally in the gastrointestinal tract (indicating that we used a good selection of bioadhesive compounds for pharmaceutical preparation of ASA + capsaicin(iods) combination, 2. The results of these phase I. examinations offer us a further possibility to carry out forthcoming phase II. and III. examinations in patients.

Rôle des estrogènes sur la physiologie et la physiopathologie du bas appareil urinaire

The aim was to review the literature on estrogens and lower urinary tract. A review of literature through the PubMed library until December 31, 2012 was carried out using the following keywords: lower urinary tract, bladder, urethra, nervous central system, innervation, female, women, estrogen, estradiol, urogenital atrophy, urinary incontinence, overactive bladder, urinary tract infection. On the bladder, estrogens are involved in the trophicity, vascularisation, alpha-adrenergic, cholinergic and muscarinic receptor density, detrusor contractility and inflammation. On the urethra, they impact vascularisation, contractility, urethral pulse and tone, anatomical and functional length. On the neurological control, they act on capsaicin-sensitive afferent fibres, neurological regeneration, nerve growth factor expression and viscerovisceral sensitisation. Estrogens play a major role on the lower urinary tract physiology and physiopathology both on the urethra and the bladder.

Brainstem Neuropeptides and Vagal Protection of the Gastric Mucosal Against Injury: Role of Prostaglandins, Nitric Oxide and Calcitonin-Gene Related Peptide in Capsaicin Afferents

Earlier experimental studies indicated that the integrity of vagal pathway was required to confer gastric protection against damaging agents. Several peptides located in the brainstem initially identified to influence vagal outflow to the stomach, as assessed by electrophysiological approach or by vagal dependent alterations of gastric secretory and motor function, were investigated for their influence in the vagal regulation of the resistance of the gastric mucosa to injury. Thyrotropin releasing hormone (TRH), or its stable TRH analog, RX-77368, injected at low doses into the cisterna magna or the dorsal motor nucleus (DMN) was the first peptide reported to protect the gastric mucosa against ethanol injury through stimulation of vagal cholinergic pathways, inducing the release of gastric prostaglandins/nitric oxide (NO) and the recruitment of efferent function of capsaicin sensitive afferent fibers containing calcitonin-gene related peptide (CGRP). Activation of endogenous TRH-TRH1 receptor signaling located in the brainstem plays a role in adaptive gastric protection against damaging agents. Since then, an expanding number of peptides, namely peptide YY, CGRP, adrenomedullin, amylin, glugacon-like peptide, opioid peptides acting on µ, δ1 or δ2 receptors, nocicpetin, nocistatin, ghrelin, leptin and TLQP-21, a peptide derived from VGF prohormone, have been reported to act in the brainstem to afford gastric protection against ethanol injury largely through similar peripheral effectors mechanisms than TRH. Therefore gastric prostaglandins and CGRP/NO pathways represent a common final mechanism through which brain peptides confer vagally mediated gastroprotection against injury. A better understanding of brain circuitries through which these peptides are released will provide new strategies to recruit integrated and multifaceted gastroprotective mechanisms.

Capsaicin prevents the hyperalgesia induced by peripheral group I mGluRs activation

Group 1 metabotropic glutamate receptors (mGluRs) are expressed in peripheral and central neural tissues and involved in peripheral and central sensitization in various pain models. However, there are limited reports that activation of peripheral group I mGluRs could evoke pain. Furthermore, any behavioral evidences could not be found out, showing what kind of afferent fibers are involved in peripheral mGluRs-mediated hyperalgesia. This study was undertaken to clarify whether peripherally injected group I mGluRs agonists could induce pain-related behaviors and capsaicin-sensitive afferent fibers might be involved in the hyperalgesia. To assess pain sensitivity, mechanical threshold for paw withdrawal response (PWT) was measured and number of spontaneous flinching behavior was counted. Intraplantar injection of group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine (DHPG) and mGluR5 agonist, (RS)-2-chloro-5-hydroxyphenyglycine (CHPG) immediately induced pain-like behaviors, such as decrease of PWT and increased number of flinchings. These agonists-induced pain-like behaviors were blocked by group I mGluRs antagonist, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) and mGluR5 antagonist, 2-methyl-6-(phenylethynyl) pyridine hydrochloride (MPEP). Perineural pretreatment of 1% capsaicin solution significantly reduced pain-related behaviors induced by DHPG and CHPG, proposing that capsaicin-sensitive primary afferent fibers could be responsible for the hyperalgesia induced by activation of peripheral group I mGluRs. This study presents the first behavioral evidence that peripheral group I mGluRs activation could induce spontaneous as well as mechanical hyperalgesia and capsaicin-sensitive afferent fiber could be implicated the group I mGluR mediated hyperalgesia.

Effect of Ovariectomy on External Urethral Sphincter Activity in Anesthetized Female Rats

The postmenopausal hypoestrogen condition is associated with various lower urinary tract dysfunctions, including frequency, urgency, stress urinary incontinence and recurrent urinary infection. We determined whether hypoestrogen induced lower urinary tract dysfunction after ovariectomy is also associated with an alteration in external urethral sphincter activity. Bilateral ovariectomy was performed in female Sprague-Dawley® rats and sham operated rats served as controls. Transvesical cystometry and external urethral sphincter electromyogram activity were monitored 4, 6 and 12 weeks after sham operation or bilateral ovariectomy and at 6 weeks in bilaterally ovariectomized rats treated with estrogen. The micturition reflex was elicited in sham operated and bilaterally ovariectomized, urethane anesthetized animals. Post-void residual urine increased and voiding efficiency decreased in rats with 4 to 12 weeks of bilateral ovariectomy. The silent period of external urethral sphincter electromyogram activity was shortened significantly and progressively at increased times after bilateral ovariectomy. These effects were prevented by estradiol treatment. As evidenced by shortening of the external urethral sphincter electromyogram silent period in ovariectomized rats, the disruption of coordination between the external urethral sphincter and the detrusor muscle could decrease urine outflow and in turn voiding efficiency. Estrogen replacement reverses these changes, suggesting that the central pathways responsible for detrusor-sphincter coordination are modulated by gonadal hormones.

Abdominal hyperalgesia in secretory phospholipase A 2-induced rat pancreatitis: Distinct roles of NK 1 receptors

We investigated the potential of secretory phospholipase A 2 (sPLA 2)-induced pancreatitis to promote abdominal hyperalgesia, as well as to depolarize sensory fibres in vitro using a grease-gap technique. Pancreatitis was induced by the injection of sPLA 2 from Crotalus durissus terrificus (sPLA 2 Cdt, 300 μg kg −1) venom into the common bile duct of rats. Pancreatic inflammatory signs, serum amylase levels and abdominal hyperalgesia were evaluated in rats treated or not with SR140333, a tachykinin NK 1 receptor antagonist. Injection of sPLA 2 Cdt caused pancreatic oedema formation and increased pancreatic neutrophil infiltration and serum amylase at 4 h, which returned to normality by 24 h, except for the neutrophil infiltration, which was still increased at this time point. Animals injected with sPLA 2 exhibited a lower withdrawal threshold to electronic von Frey stimulation in the upper abdominal region at 4 h, but not 24 h, post-injection when compared with saline-injected rats. Pre-treatment of animals with SR140333 significantly reduced the sPLA 2 Cdt-induced abdominal hyperalgesia, without affecting the other parameters. Neither sPLA 2 Cdt nor sPLA 2 from Naja mocambique mocambique venom depolarized capsaicin-sensitive sensory fibres from rat vagus nerve, but they decreased the propagated compound action potentials in both A and C fibres. These data show for the first time that NK 1 receptors play an important role in the early abdominal hyperalgesia in a rat model of sPLA 2-induced pancreatitis, suggesting that these receptors are of importance in the development of pain in the pancreatitis condition. We also provide evidence that sPLA 2s do not directly depolarize sensory fibres in vitro.

Role of TRPV1 in nociception and edema induced by monosodium urate crystals in rats

Gout is characterized by the deposition of monosodium urate (MSU) crystals. Despite being one of the most painful forms of arthritis, gout and the mechanisms responsible for its acute attacks are poorly understood. In the present study, we found that MSU caused dose-related nociception (ED50 [ie, the necessary dose of MSU to elicit 50% of the response relative to the control value]=0.04 [95% confidence interval 0.01–0.11]mg/paw) and edema (ED50=0.08 [95% confidence interval 0.04–0.16]mg/paw) when injected into the hind paw of rats. Treatment with the selective TRPV1 receptor (also known as capsaicin receptor and vanilloid receptor-1) antagonists SB366791 or AMG9810 largely prevented nociceptive and edematogenic responses to MSU. Moreover, the desensitization of capsaicin-sensitive afferent fibers as well as pretreatment with the tachykinin NK1 receptor antagonist RP 67580 also significantly prevented MSU-induced nociception and edema. Once MSU was found to induce mast cell stimulation, we investigated the participation of these cells on MSU effects. Prior degranulation of mast cells by repeated treatment with the compound 48/80 decreased MSU-induced nociception and edema or histamine and serotonin levels in the injected tissue. Moreover, pretreatment with the mast cell membrane stabilizer cromolyn effectively prevented nociceptive and edematogenic responses to MSU. MSU induced a release of histamine, serotonin, and tryptase in the injected tissue, confirming mast cell degranulation. Furthermore, the antagonism of histaminergic H1 and serotoninergic receptors decreased the edema, but not the nociception of MSU. Finally, the prevention of the tryptase activity was capable of largely reducing both MSU-induced nociception and edema. Collectively, the present findings demonstrate that MSU produces nociceptive and edematogenic responses mediated by TRPV1 receptor activation and mast cell degranulation.Monosodium urate crystals produce nociceptive and edematogenic response mediated by TRPV1 receptor activation and mast cell degranulation.

W1357 Capsaicin Sensitive Afferent Fibres Innervating the Portal Vein are Activated by Glucagon-Like Peptide 1 (GLP-1) Receptor Stimulation

W1357 Capsaicin Sensitive Afferent Fibres Innervating the Portal Vein are Activated by Glucagon-Like Peptide 1 (GLP-1) Receptor Stimulation

Phenylpyrazolone derivatives inhibit gastric emptying in rats by a capsaicin-sensitive afferent pathway

Dipyrone (Dp), 4-aminoantipyrine (AA) and antipyrine (At) administered iv and Dp administered icv delay gastric emptying (GE) in rats. The participation of capsaicin (Cps)-sensitive afferent fibers in this phenomenon was evaluated. Male Wistar rats were pretreated sc with Cps (50 mg/kg) or vehicle between the first and second day of life and both groups were submitted to the eye-wiping test. GE was determined in these animals at the age of 8/9 weeks (weight: 200-300 g). Ten minutes before the study, the animals of both groups were treated iv with Dp, AA or At (240 micromol/kg), or saline; or treated icv with Dp (4 micromol/animal) or saline. GE was determined 10 min after treatment by measuring % gastric retention (GR) of saline labeled with phenol red 10 min after orogastric administration. Percent GR (mean +/- SEM, N = 8) in animals pretreated with Cps and treated with Dp, AA or At (35.8 +/- 3.2, 35.4 +/- 2.2, and 35.6 +/- 2%, respectively) did not differ from the GR of saline-treated animals pretreated with vehicle (36.8 +/- 2.8%) and was significantly lower than in animals pretreated with vehicle and treated with the drugs (52.1 +/- 2.8, 66.2 +/- 4, and 55.8 +/- 3%, respectively). The effect of icv administration of Dp (N = 6) was not modified by pretreatment with Cps (63.3 +/- 5.7%) compared to Dp-treated animals pretreated with vehicle (62.3 +/- 2.4%). The results suggest the participation of capsaicin-sensitive afferent fibers in the delayed GE induced by iv administration of Dp, AA and At, but not of icv Dp.

Capsaicin-sensitive sensory nerve fibers contribute to the generation and maintenance of skeletal fracture pain

Although skeletal pain can have a marked impact on a patient's functional status and quality of life, relatively little is known about the specific populations of peripheral nerve fibers that drive non-malignant bone pain. In the present report, neonatal male Sprague–Dawley rats were treated with capsaicin or vehicle and femoral fracture was produced when the animals were young adults (15–16 weeks old). Capsaicin treatment, but not vehicle, resulted in a significant (>70%) depletion in the density of calcitonin-gene related peptide positive (CGRP+) sensory nerve fibers, but not 200 kDa neurofilament H positive (NF200+) sensory nerve fibers in the periosteum. The periosteum is a thin, cellular and fibrous tissue that tightly adheres to the outer surface of all but the articulated surface of bone and appears to play a pivotal role in driving fracture pain. In animals treated with capsaicin, but not vehicle, there was a 50% reduction in the severity, but no change in the time course, of fracture-induced skeletal pain–related behaviors as measured by spontaneous flinching, guarding and weight bearing. These results suggest that both capsaicin-sensitive (primarily CGRP+ C-fibers) and capsaicin-insensitive (primarily NF200+ A-delta fibers) sensory nerve fibers participate in driving skeletal fracture pain. Skeletal pain can be a significant impediment to functional recovery following trauma-induced fracture, osteoporosis-induced fracture and orthopedic surgery procedures such as knee and hip replacement. Understanding the specific populations of sensory nerve fibers that need to be targeted to inhibit the generation and maintenance of skeletal pain may allow the development of more specific mechanism-based therapies that can effectively attenuate acute and chronic skeletal pain.

S1732 Experimental Colitis in Rats Increases TNF-α and IL-10 mRNA Expression in Distant Intestinal Sites Through Capsaicin Sensitive Primary Afferent Fibers

S1732 Experimental Colitis in Rats Increases TNF-α and IL-10 mRNA Expression in Distant Intestinal Sites Through Capsaicin Sensitive Primary Afferent Fibers

Feeding pattern after intraperitoneal capsaicin desensitization in rats

Event Abstract Back to Event Feeding pattern after intraperitoneal capsaicin desensitization in rats Peter Cseplo1, Andras Garami1, Margit Solymár1, Marta Balasko1, Erika Petervari1 and Miklos Szekely1* 1 University of Pecs, Department of Pathophysiology and Gerontology, Hungary In regulation of satiety and hunger, similarly as in the regulation of postprandial hypermetabolism or fasting hypometabolism there may be a role for neural information from the abdominal cavity. Capsaicin-sensitive afferent abdominal vagal fibers may influence both onset and cessation of feeding, i.e. the feeding pattern, besides influencing the total amount of food consumed. In the present experiments strictly the local (abdominal) afferent fibers were desensitized by intraperitoneal (IP) application of small dose capsaicin. For this purpose, 4-months-old male Wistar rats were injected IP with 2+3 mg/kg capsaicin a few days after IP implantation of telemetric sensors of body temperature, heart rate and spontaneous activity. The animals were placed into the biotelemetric system to record these signals along with feeding frequency (FF) and feeding duration (FD) registered by the infrared Feeding monitor. The amount of consumed food was measured manually. One week after the desensitization a 5-days-long fasting followed to check the usually defective hypometabolic adaptation to fasting in desensitized animals (enhanced tendency for hyperthermic periods), then the food was returned and FD, FF and the food consumption were analyzed. During the first hour of re-feeding, the desensitized rats ate significantly more than the controls and the difference was sustained for well over 3 hours. As expected, in desensitized rats the FD was longer in some fractions of the first hour, but FF was also higher. Besides, the elevation of these parameters was more prolonged. Apparently, IP neural signals influence feeding behavior. Support: OTKA 49321 Conference: 12th Meeting of the Hungarian Neuroscience Society, Budapest, Hungary, 22 Jan - 24 Jan, 2009. Presentation Type: Poster Presentation Topic: Homeostatic regulatory mechanisms Citation: Cseplo P, Garami A, Solymár M, Balasko M, Petervari E and Szekely M (2009). Feeding pattern after intraperitoneal capsaicin desensitization in rats. Front. Syst. Neurosci. Conference Abstract: 12th Meeting of the Hungarian Neuroscience Society. doi: 10.3389/conf.neuro.01.2009.04.006 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 02 Mar 2009; Published Online: 02 Mar 2009. * Correspondence: Miklos Szekely, University of Pecs, Department of Pathophysiology and Gerontology, Pecs, Hungary, miklos.szekely@aok.pte.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Peter Cseplo Andras Garami Margit Solymár Marta Balasko Erika Petervari Miklos Szekely Google Peter Cseplo Andras Garami Margit Solymár Marta Balasko Erika Petervari Miklos Szekely Google Scholar Peter Cseplo Andras Garami Margit Solymár Marta Balasko Erika Petervari Miklos Szekely PubMed Peter Cseplo Andras Garami Margit Solymár Marta Balasko Erika Petervari Miklos Szekely Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Sensory Denervation Reduces Visceral Hypersensitivity in Adult Rats Exposed to Chronic Unpredictable Stress: Evidences of Neurogenic Inflammation

The purpose of this study is to provide evidence of neurogenic inflammation in chronic unpredictable stressed rats with the changes of visceral sensitivity, number of mast cells, and close proximity among mast cell-nerve-blood vessels. We found that (1) capsaicin denervation blocked stress-induced increase of visceral sensitivity, while doxantrazole presented a partial blocking; (2) capsaicin denervation blocked stress-induced enhancement of the proximity of mast cell-nerve fiber-blood vessels and blood vessel damage, while doxantrazole showed no effects on these; (3) doxantrazole blocked stress-induced increases of the MPO activity, the number and the degranulation of mast cells in the colon; (4) sensory denervation and doxantrazole had no effects on stress-induced behavioral inhibition. These results suggest that capsaicin-sensitive sensory fibers play a key role in stress-induced visceral hypersensitivity and the ultrastructural changes, mast cells play an important role in the generation of stress-induced colon inflammation.

Excitatory and inhibitory urinary bladder reflexes induced by stimulation of cervicovaginal capsaicin-sensitive sensory fibers in rats

We have investigated the effect of intravaginal application of capsaicin on micturition reflex in female rats. Urinary bladder contractility was measured by transurethral pressure recording at isovolumetric and subthreshold conditions in anaesthetized rats. The intravaginal application of capsaicin (15 microg/50 microl rat) induced reproducible bladder phasic contractions, without desensitization upon repeated applications, that were blocked by intravenous atropine (1 mg/kg) or hexamethonium (5 mg/kg) and prevented by removal of paracervical ganglia or systemic capsaicin pretreatment (125 mg/kg, s.c.). The inhibition of sympathetic transmission by guanethidine (30 mg/kg, s.c.) produced significant increase of the bladder reflex contractions activated by intravaginal capsaicin. Intravenous administration of the TRPV1 antagonist, capsazepine (3 mg/kg), significantly reduced the excitatory reflex response to capsaicin. Intravaginal administration of capsaicin (15 microg/50 microl), during distension-induced reflex bladder contractions, produced a transient block of reflexes, unaffected by guanethidine pretreatment. In conclusion, the stimulation of capsaicin-sensitive sensory nerve endings in the rat cervix-vagina induced a dual excitatory or inhibitory bladder response in anaesthetized female rats depending on the degree of bladder distension.

Capsaicin-sensitive afferent fibers mediate the protective effect of electrical stimulation of paraventricular nucleus against gastric ischemia-reperfusion injury in rats

Capsaicin-sensitive afferent fibers mediate the protective effect of electrical stimulation of paraventricular nucleus against gastric ischemia-reperfusion injury in rats