scholarly journals Silencing Transient Receptor Potential Vanilloid Receptor Subtype I–containing Sensory Neurons to Treat Bone Cancer Pain

2016 ◽  
Vol 125 (1) ◽  
pp. 17-19
Author(s):  
Christopher M. Peters
Keyword(s):  
Cancer Pain ◽  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Bone Cancer ◽  
Receptor Potential ◽  
Vanilloid Receptor ◽  
Bone Cancer Pain ◽  
Receptor Subtype ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

scholarly journals Propofol Restores Transient Receptor Potential Vanilloid Receptor Subtype-1 Sensitivity via  Activation of Transient Receptor Potential Ankyrin Receptor Subtype-1 in Sensory Neurons

2011 ◽  
Vol 114 (5) ◽  
pp. 1169-1179 ◽  
Author(s):  
Hongyu Zhang ◽  
Peter J. Wickley ◽  
Sayantani Sinha ◽  
Ian N. Bratz ◽  
Derek S. Damron
Keyword(s):  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Vanilloid Receptor ◽  
Receptor Subtype ◽  
Transient Receptor Potential Vanilloid ◽  
Peripheral Sensitization ◽  
Drg Neurons ◽  
Trpv1 Receptors ◽  
Transient Receptor

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.

scholarly journals Characterization of acid signaling in rat vagal pulmonary sensory neurons

2006 ◽  
Vol 291 (1) ◽  
pp. L58-L65 ◽  
Author(s):  
Qihai Gu ◽  
Lu-Yuan Lee
Keyword(s):  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Low Ph ◽  
Receptor Subtype ◽  
Transient Receptor Potential Vanilloid ◽  
Inward Current ◽  
Transient Component ◽  
Current Voltage Curve ◽  
Transient Receptor

Local tissue acidosis frequently occurs in airway inflammatory and ischemic conditions. The effect of physiological/pathophysiological-relevant low pH (7.0–5.5) on isolated rat vagal pulmonary sensory neurons was investigated using whole cell perforated patch-clamp recordings. In voltage-clamp recordings, vagal pulmonary sensory neurons exhibited distinct pH sensitivities and different phenotypes of inward current in responding to acidic challenge. The current evoked by lowering the pH of extracellular solution to 7.0 consisted of only a transient, rapidly inactivating component with small amplitude. The amplitude of this transient current increased when the proton concentration was elevated. In addition, a slow, sustained inward current began to emerge when pH was reduced to <6.5. The current-voltage curve indicated that the transient component of acid-evoked current was carried predominantly by Na+. This transient component was dose-dependently inhibited by amiloride, a common blocker of acid-sensing ion channels (ASICs), whereas the sustained component was significantly attenuated by capsazepine, a selective antagonist of transient receptor potential vanilloid receptor subtype-1 (TRPV1). The two components of acid-evoked current also displayed distinct recovery kinetics from desensitization. Furthermore, in current-clamp recordings, transient extracellular acidification depolarized the membrane potential and generated action potentials in these isolated neurons. In summary, our results have demonstrated that low pH can stimulate rat vagal pulmonary sensory neurons through the activation of both ASICs and TRPV1. The relative roles of these two current species depend on the range of pH and vary between neurons.

scholarly journals Baicalin Ameliorates Bone Cancer Pain by Suppressing TRPV1 in Rat Dorsal Root Ganglia

2020 ◽  
Vol 15 (1) ◽  
pp. 1934578X1989956 ◽  
Author(s):  
Ping Li ◽  
Ying Bi ◽  
Yuchun Deng ◽  
Donglin Xiong ◽  
Anxue Li
Keyword(s):  
Cancer Pain ◽  
Analgesic Effect ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Bone Cancer ◽  
Receptor Potential ◽  
Bone Cancer Pain ◽  
Flavonoid Compound ◽  
Transient Receptor

Bone cancer pain is characterized by moderate to severe ongoing pain that commonly requires the use of opiates, which could produce tolerance or addiction. Baicalin is a flavonoid compound extracted from Huang Qin, possesses antioxidant properties, and has an analgesic effect on nitroglycerin-induced migraine in rats and neuropathic pain in spinal nerve ligation rats. However, the effect of baicalin on bone cancer pain is still unclear. Therefore, the aim of this study is to examine the analgesic effect of baicalin in a rat model of bone cancer pain. Bone cancer pain animal model was created by tumor cell implantation (TCI). Animal behaviors were measured using a set of mechanical or electronic von Frey apparatus and hot plate. mRNA expression and inflammation cytokine levels were examined by Quantitative polymerase chain reaction (qPCR) and enzyme linked immunosorbent assay (ELISA) methods. Baicalin suppressed the upregulation of transient receptor potential vanilloid 1 (TRPV1), but not transient receptor potential A1 in dorsal root ganglion (DRG) of TCI rats. In addition, the phosphorylation of extracellular regulated protein kinases (ERK) was also suppressed by baicalin injection in DRG of TCI rats. Our results revealed that baicalin might play a promising analgesic role by preventing the upregulation of TRPV1 in DRG of TCI rats. Baicalin administration prevented the progress of bone cancer pain and reduced mechanical allodynia and thermal hyperalgesia. Our study clearly established a novel role of baicalin as an analgesic agent for bone cancer pain. And the analgesic role of baicalin in bone cancer pain might involve a TRPV1.

scholarly journals 17β-Estradiol Activates Estrogen Receptor β-Signalling and Inhibits Transient Receptor Potential Vanilloid Receptor 1 Activation by Capsaicin in Adult Rat Nociceptor Neurons

Endocrinology ◽  
2008 ◽  
Vol 149 (11) ◽  
pp. 5540-5548 ◽  
Author(s):  
Shenghong Xu ◽  
Ying Cheng ◽  
Janet R. Keast ◽  
Peregrine B. Osborne
Keyword(s):  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Vanilloid Receptor ◽  
Female Rats ◽  
Transient Receptor Potential Vanilloid ◽  
Adult Rat ◽  
Vanilloid Receptor 1 ◽  
17Β Estradiol ◽  
Transient Receptor

There is mounting evidence that estrogens act directly on the nervous system to affect the severity of pain. Estrogen receptors (ERs) are expressed by sensory neurons, and in trigeminal ganglia, 17β-estradiol can indirectly enhance nociception by stimulating expression and release of prolactin, which increases phosphorylation of the nociceptor transducer transient receptor potential vanilloid receptor 1 (TRPV1). Here, we show that 17β-estradiol acts directly on dorsal root ganglion (DRG) sensory neurons to reduce TRPV1 activation by capsaicin. Capsaicin-induced cobalt uptake and the maximum TRPV1 current induced by capsaicin were inhibited when isolated cultured DRGs neurons from adult female rats were exposed to 17β-estradiol (10–100 nm) overnight. There was no effect of 17β-estradiol on capsaicin potency, TRPV1 activation by protons (pH 6–4), and P2X currents induced by α,β-methylene-ATP. Diarylpropionitrile (ERβ agonist) also inhibited capsaicin-induced TRPV1 currents, whereas propylpyrazole triol (ERα agonist) and 17α-estradiol (inactive analog) were inactive, and 17β-estradiol conjugated to BSA (membrane-impermeable agonist) caused a small increase. TRPV1 inhibition was antagonized by tamoxifen (1 μm), but ICI182870 (10 μm) was a potent agonist and mimicked 17β-estradiol. We conclude that TRPV1 in DRG sensory neurons can be inhibited by a nonclassical estrogen-signalling pathway that is downstream of intracellular ERβ. This affects the vanilloid binding site targeted by capsaicin but not the TRPV1 activation site targeted by protons. These actions could curtail the nociceptive transducer functions of TRPV1 and limit chemically induced nociceptor sensitization during inflammation. They are consistent with clinical reports that female pelvic pain can increase after reductions in circulating estrogens.

scholarly journals Systemic QX-314 Reduces Bone Cancer Pain through Selective Inhibition of Transient Receptor Potential Vanilloid Subfamily 1–expressing Primary Afferents in Mice

2016 ◽  
Vol 125 (1) ◽  
pp. 204-218 ◽  
Author(s):  
Satoshi Fuseya ◽  
Katsumi Yamamoto ◽  
Hitoshi Minemura ◽  
Satoshi Yamaori ◽  
Tomoyuki Kawamata ◽  
...  
Keyword(s):  
Cancer Pain ◽  
Transient Receptor Potential ◽  
Bone Cancer ◽  
Receptor Potential ◽  
Adenosine Monophosphate ◽  
Selective Inhibition ◽  
Dorsal Root Ganglion Neurons ◽  
Bone Cancer Pain ◽  
Transient Receptor Potential Vanilloid ◽  
Ganglion Neurons

Abstract Background The aim of this study was to determine whether systemic administration of QX-314 reduces bone cancer pain through selective inhibition of transient receptor potential vanilloid subfamily 1 (TRPV1)–expressing afferents. Methods A mouse model of bone cancer pain was used. The authors examined the effects of bolus (0.01 to 3 mg/kg, n = 6 to 10) and continuous (5 mg kg−1 h−1, n = 5) administration of QX-314 on both bone cancer pain–related behaviors and phosphorylated cyclic adenosine monophosphate response element–binding protein expression in dorsal root ganglion neurons (n = 3 or 6) and the effects of ablation of TRPV1-expressing afferents on bone cancer pain–related behaviors (n = 10). Results The numbers of flinches indicative of ongoing pain in QX-314–treated mice were smaller than those in vehicle-treated mice at 10 min (3 mg/kg, 4 ± 3; 1 mg/kg, 5 ± 3 vs. 12 ± 3; P &lt; 0.001; n = 8 to 9), 24 h (3 ± 2 vs. 13 ± 3, P &lt; 0.001), and 48 h (4 ± 1 vs. 12 ± 2, P &lt; 0.001; n = 5 in each group) after QX-314 administration, but impaired limb use, weight-bearing including that examined by the CatWalk system, and rotarod performance indicative of movement-evoked pain were comparable. QX-314 selectively inhibited the increase in phosphorylated cyclic adenosine monophosphate response element–binding protein expression in TRPV1-positive, but not in TRPV1-negative, dorsal root ganglion neurons compared to that in the case of vehicle administration (32.2 ± 3.0% vs. 52.6 ± 5.9%, P &lt; 0.001; n = 6 in each group). Ablation of TRPV1-expressing afferents mimicked the effects of QX-314. Conclusion This study showed that systemic administration of QX-314 in mice inhibits some behavioral aspects of bone cancer pain through selective inhibition of TRPV1-expressing afferents without coadministration of TRPV1 agonists.

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