Effect of Surgical and Chemical Sensory Denervation on Non-neural Expression of the Transient Receptor Potential Vanilloid 1 (TRPV1) Receptors in the Rat

2012 ◽  
Vol 48 (3) ◽  
pp. 795-803 ◽  
Author(s):  
József Kun ◽  
Zsuzsanna Helyes ◽  
Anikó Perkecz ◽  
Ágnes Bán ◽  
Beáta Polgár ◽  
...  
Author(s):  
Sanjeev K. Singh ◽  
M. S. Muthu ◽  
Ravindran Revand ◽  
M. B. Mandal

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in regulation of cardiorespiratory (CVR) system. Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 µM) in the absence or presence of antagonists. Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin-induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 µg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.


2010 ◽  
Vol 42 (1) ◽  
pp. 80-88 ◽  
Author(s):  
Istvan Szitter ◽  
Gabor Pozsgai ◽  
Katalin Sandor ◽  
Krisztian Elekes ◽  
Agnes Kemeny ◽  
...  

2011 ◽  
Vol 114 (5) ◽  
pp. 1169-1179 ◽  
Author(s):  
Hongyu Zhang ◽  
Peter J. Wickley ◽  
Sayantani Sinha ◽  
Ian N. Bratz ◽  
Derek S. Damron

Background Cross talk between peripheral nociceptors belonging to the transient receptor potential vanilloid receptor subtype-1 (TRPV1) and ankyrin subtype-1 (TRPA1) family has been demonstrated recently. Moreover, the intravenous anesthetic propofol has directly activates TRPA1 receptors and indirectly restores sensitivity of TRPV1 receptors in dorsal root ganglion (DRG) sensory neurons. Our objective was to determine the extent to which TRPA1 activation is involved in mediating the propofol-induced restoration of TRPV1 sensitivity. Methods Mouse DRG neurons were isolated by enzymatic dissociation and grown for 24 h. F-11 cells were transfected with complementary DNA for both TRPV1 and TRPA1 or TRPV1 only. The intracellular Ca concentration was measured in individual cells via fluorescence microscopy. After TRPV1 desensitization with capsaicin (100 nM), cells were treated with propofol (1, 5, and 10 μM) alone or with propofol in the presence of the TRPA1 antagonist, HC-030031 (0.5 μM), or the TRPA1 agonist, allyl isothiocyanate (AITC; 100 μM); capsaicin was then reapplied. Results In DRG neurons that contain both TRPV1 and TRPA1, propofol and AITC restored TRPV1 sensitivity. However, in DRG neurons containing only TRPV1 receptors, exposure to propofol or AITC after desensitization did not restore capsaicin-induced TRPV1 sensitivity. Similarly, in F-11 cells transfected with both TRPV1 and TRPA1, propofol and AITC restored TRPV1 sensitivity. However, in F-11 cells transfected with TRPV1 only, neither propofol nor AITC was capable of restoring TRPV1 sensitivity. Conclusions These data demonstrate that propofol restores TRPV1 sensitivity in primary DRG neurons and in cultured F-11 cells transfected with both the TRPV1 and TRPA1 receptors via a TRPA1-dependent process. Propofol's effects on sensory neurons may be clinically important and may contribute to peripheral sensitization to nociceptive stimuli in traumatized tissue.


2007 ◽  
Vol 292 (5) ◽  
pp. L1173-L1181 ◽  
Author(s):  
Zsuzsanna Helyes ◽  
Krisztián Elekes ◽  
József Németh ◽  
Gábor Pozsgai ◽  
Katalin Sándor ◽  
...  

Airways are densely innervated by capsaicin-sensitive sensory neurons expressing transient receptor potential vanilloid 1 (TRPV1) receptors/ion channels, which play an important regulatory role in inflammatory processes via the release of sensory neuropeptides. The aim of the present study was to investigate the role of TRPV1 receptors in endotoxin-induced airway inflammation and consequent bronchial hyperreactivity with functional, morphological, and biochemical techniques using receptor gene-deficient mice. Inflammation was evoked by intranasal administration of Escherichia coli lipopolysaccharide (60 μl, 167 μg/ml) in TRPV1 knockout (TRPV1−/−) mice and their wild-type counterparts (TRPV1+/+) 24 h before measurement. Airway reactivity was assessed by unrestrained whole body plethysmography, and its quantitative indicator, enhanced pause (Penh), was calculated after inhalation of the bronchoconstrictor carbachol. Histological examination and spectrophotometric myeloperoxidase measurement was performed from the lung. Somatostatin concentration was measured in the lung and plasma with radioimmunoassay. Bronchial hyperreactivity, histological lesions (perivascular/peribronchial edema, neutrophil/macrophage infiltration, goblet cell hyperplasia), and myeloperoxidase activity were significantly greater in TRPV−/− mice. Inflammation markedly elevated lung and plasma somatostatin concentrations in TRPV1+/+ but not TRPV1−/− animals. In TRPV1−/− mice, exogenous administration of somatostatin-14 (4 × 100 μg/kg ip) diminished inflammation and hyperreactivity. Furthermore, in wild-type mice, antagonizing somatostatin receptors by cyclo-somatostatin (4 × 250 μg/kg ip) increased these parameters. This study provides the first evidence for a novel counterregulatory mechanism during endotoxin-induced airway inflammation, which is mediated by somatostatin released from sensory nerve terminals in response to activation of TRPV1 receptors of the lung. It reaches the systemic circulation and inhibits inflammation and consequent bronchial hyperreactivity.


2014 ◽  
pp. S225-S236 ◽  
Author(s):  
D. SPICAROVA ◽  
V. NERANDZIC ◽  
J. PALECEK

The structure, expression and function of the transient receptor potential vanilloid 1 (TRPV1) receptor were intensively studied since the cloning in 1997 and TRPV1 receptors are now considered to act as transducers and molecular integrators of nociceptive stimuli in the periphery. In contrast, spinal TRPV1 receptors were studied less extensively and their role in pain modulation is still not fully understood. This short review is a follow up on our previous summary in this area (Spicarova and Palecek 2008). The aim was to review preferentially the most recent findings concerning the role of the spinal TRPV1 receptors, published within the last five years. The update is given on the expression and function of the spinal TRPV1 receptors, their activation by endogenous agonists, interaction between the endocannabinoid and endovanillod system and possible role of the spinal TRPV1 receptors in pathological pain states. There is now mounting evidence that TRPV1 receptors may be an important element in modulation of nociceptive information at the spinal cord level and represent an interesting target for analgesic therapy.


2008 ◽  
Vol 294 (5) ◽  
pp. R1517-R1523 ◽  
Author(s):  
Youping Wang ◽  
Martin Novotný ◽  
Veronika Quaiserová-Mocko ◽  
Greg M. Swain ◽  
Donna H. Wang

This study was designed to test the hypothesis that the transient receptor potential vanilloid type 1 (TRPV1) channel, expressed primarily in sensory nerves, and substance P (SP), released by sensory nerves, play a protective role against lipopolysaccharide (LPS)-induced hypotension. LPS (10 mg/kg iv) elicited tachycardia and hypotension in anesthetized male Wistar rats, which peaked at 10 min and gradually recovered 1 h after the injection. Blockade of TRPV1 with its selective antagonist capsazepine (CAPZ, 3 mg/kg iv) impaired recovery given that the fall in mean arterial pressure (MAP) was greater 1 h after CAPZ plus LPS injections compared with LPS injection alone (45 ± 5 vs. 25 ± 4 mmHg, P < 0.05). Blockade of the neurokinin 1 (NK1) receptor with its selective antagonists RP-67580 (5 mg/kg iv) or L-733,060 (4 mg/kg iv) prevented recovery, considering that falls in MAP were not different 1 h after injections of NK1 antagonists plus LPS from their peak decreases (66 ± 9 vs. 74 ± 5 mmHg or 60 ± 7 vs. 69 ± 3 mmHg, respectively, P > 0.05). LPS increased plasma SP, norepinephrine (NE), and epinephrine (Epi) levels compared with vehicles, and the increases in plasma SP, NE, and Epi were significantly inhibited by CAPZ or RP-67580. The survival rate at 24 or 48 h after LPS injection (20 mg/kg ip) was lower in conscious rats pretreated with CAPZ or RP-67580 compared with rats treated with LPS alone ( P < 0.05). Thus our results show that the TRPV1, possibly via triggering release of SP which activates the NK1 and stimulates the sympathetic axis, plays a protective role against endotoxin-induced hypotension and mortality, suggesting that TRPV1 receptors are essential in protecting vital organ perfusion and survival during the endotoxic condition.


2020 ◽  
Vol 318 (1) ◽  
pp. L89-L97
Author(s):  
Wan Wei ◽  
Xiuping Gao ◽  
Lei Zhao ◽  
Jianguo Zhuang ◽  
Yang Jiao ◽  
...  

Liquiritin apioside (LA), a main flavonoid component of licorice, reportedly suppresses cough responses to inhalation of aerosolized capsaicin [CAP; a stimulant to transient receptor potential vanilloid 1 (TRPV1)] in conscious guinea pigs via acting on peripheral nerves. However, the evidence of LA having a direct effect on airway sensory fibers is lacking. Considering the important role laryngeal chemoreceptors and mechanoreceptors play in triggering apnea and cough, we studied whether LA suppressed the apneic responses to stimulation of these receptors via directly acting on the superior laryngeal nerve (SLN). Intralaryngeal delivery of chemical [CAP, HCl, and distilled water (DW)] and mechanical [an air-pulse (AP)] stimulations was applied in anesthetized rat pups to evoke the apnea. These stimuli were repeated after intralaryngeal LA treatment or peri-SLN LA treatment to determine the direct effect of LA on the SLN. Our results showed that all stimuli triggered an immediate apnea. Intralaryngeal LA treatment significantly attenuated the apneic response to chemical but not mechanical stimulations. The same attenuation was observed after peri-SLN LA treatment. Owing that TRPV1 receptors of laryngeal C fibers are responsible for the CAP-triggered apneas, the LA impact on the activity of laryngeal C neurons retrogradely traced by DiI was subsequently studied using a patch-clamp approach. LA pretreatment significantly altered the electrophysiological kinetics of CAP-induced currents in laryngeal C neurons by reducing their amplitudes, increasing the rise times, and prolonging the decay times. In conclusion, our results, for the first time, reveal that LA suppresses the laryngeal chemoreceptor-mediated apnea by directly acting on the SLN (TRPV1 receptors of laryngeal C fibers).


2009 ◽  
Vol 106 (4) ◽  
pp. 1142-1152 ◽  
Author(s):  
You Shuei Lin ◽  
Ruei-Lung Lin ◽  
Mauo-Ying Bien ◽  
Ching-Yin Ho ◽  
Yu Ru Kou

Anandamide (AEA), an arachidonic acid derivative produced during inflammatory conditions, is an endogenous agonist of both transient receptor potential vanilloid 1 (TRPV1) receptors and cannabinoid CB1 receptors. Sensitization of capsaicin-sensitive lung vagal afferent (CSLVA) fibers by chemical mediators is important in the pathogenesis of hyperreactive airway diseases. We investigated the effect of the intravenous infusion of AEA (2 mg·kg−1·ml−1, 0.5 ml/min for 2 min) on the sensitivity of CSLVA fibers to chemical and mechanical stimulation in anesthetized rats. In artificially ventilated rats, AEA infusion only mildly elevated the baseline activity of CSLVA fibers. However, CSLVA fiber responses to right atrial injection of capsaicin, AEA, or adenosine and to lung inflation (tracheal pressure = 30 cmH2O) were all markedly potentiated during AEA infusion, which reverted 20 min after termination of the infusion. The potentiating effect on the sensitivity of CSLVA fibers to adenosine injection or lung inflation was completely blocked by pretreatment with capsazepine (a TRPV1 receptor antagonist) but was unaffected by pretreatment with AM281 (a CB1 receptor antagonist). In spontaneously breathing rats, right atrial injection of adenosine evoked an apneic response that is presumably mediated through CSLVA fibers. Similarly, the adenosine-evoked apneic response was potentiated during AEA infusion, and this potentiating effect was also completely prevented by pretreatment with capsazepine. These results suggest that AEA infusion at the dose tested produces a mild activation of TRPV1 receptors and this nonspecifically increases CSLVA fiber sensitivity to chemical and mechanical stimulation.


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