scholarly journals Neurotrophin-3 Suppresses Thermal Hyperalgesia Associated with Neuropathic Pain and Attenuates Transient Receptor Potential Vanilloid Receptor-1 Expression in Adult Sensory Neurons

2005 ◽  
Vol 25 (3) ◽  
pp. 758-767 ◽  
Author(s):  
T. D. Wilson-Gerwing
Keyword(s):  
Neuropathic Pain ◽  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Vanilloid Receptor ◽  
Transient Receptor Potential Vanilloid ◽  
Vanilloid Receptor 1 ◽  
Neurotrophin 3 ◽  
Transient Receptor

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 Differential Effects of Peripheral versus  Central Coadministration of QX-314 and Capsaicin on Neuropathic Pain in Rats

2012 ◽  
Vol 117 (2) ◽  
pp. 365-380 ◽  
Author(s):  
Jun Shen ◽  
Lyle E. Fox ◽  
Jianguo Cheng
Keyword(s):  
Neuropathic Pain ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Intrathecal Administration ◽  
Vanilloid Receptor ◽  
Transient Receptor Potential Vanilloid ◽  
Spontaneous Pain ◽  
Analgesic Effects ◽  
Vanilloid Receptor 1 ◽  
Transient Receptor

Background Neuropathic pain is common and difficult to treat. Recently a technique was developed to selectively inhibit nociceptive inputs by simultaneously applying two drugs: capsaicin, a transient receptor potential vanilloid receptor-1 channel activator, and QX-314, a lidocaine derivative that intracellularly blocks sodium channels. We used this technique to investigate whether transient receptor potential vanilloid receptor 1-expressing nociceptors contribute to neuropathic pain. Methods The rat chronic constriction injury model was used to induce neuropathic pain in order to test the analgesic effects of both peripheral (perisciatic) and central (intrathecal) administration of the QX-314/capsaicin combination. The Hargreaves and von Frey tests were used to monitor evoked pain-like behaviors and visual observations were used to rank spontaneous pain-like behaviors. Results Perisciatic injections of the QX-314/capsaicin combination transiently increased the withdrawal thresholds by approximately 3-fold, for mechanical and thermal stimuli in rats (n = 6/group) with nerve injuries suggesting that peripheral transient receptor potential vanilloid receptor 1-expressing nociceptors contribute to neuropathic pain. In contrast, intrathecal administration of the QX-314/capsaicin combination did not alleviate pain-like behaviors (n = 5/group). Surprisingly, intrathecal QX-314 alone (n = 9) or in combination with capsaicin (n = 8) evoked spontaneous pain-like behaviors. Conclusions Data from the perisciatic injections suggested that a component of neuropathic pain was mediated by peripheral nociceptive inputs. The role of central nociceptive terminals could not be determined because of the severe side effects of the intrathecal drug combination. We concluded that only peripheral blockade of transient receptor potential vanilloid receptor 1-expressing nociceptive afferents by the QX-314/capsaicin combination was effective at reducing neuropathic allodynia and hyperalgesia.

scholarly journals The Calcium Channel α2δ1 Subunit: Interactional Targets in Primary Sensory Neurons and Role in Neuropathic Pain

2021 ◽  
Vol 15 ◽  
Author(s):  
Wenqiang Cui ◽  
Hongyun Wu ◽  
Xiaowen Yu ◽  
Ting Song ◽  
Xiangqing Xu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Calcium Channel ◽  
Sensory Neurons ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Peripheral Sensitization ◽  
Primary Sensory Neurons ◽  
Transient Receptor ◽  
Underlying Mechanisms

Neuropathic pain is mainly triggered after nerve injury and associated with plasticity of the nociceptive pathway in primary sensory neurons. Currently, the treatment remains a challenge. In order to identify specific therapeutic targets, it is necessary to clarify the underlying mechanisms of neuropathic pain. It is well established that primary sensory neuron sensitization (peripheral sensitization) is one of the main components of neuropathic pain. Calcium channels act as key mediators in peripheral sensitization. As the target of gabapentin, the calcium channel subunit α2δ1 (Cavα2δ1) is a potential entry point in neuropathic pain research. Numerous studies have demonstrated that the upstream and downstream targets of Cavα2δ1 of the peripheral primary neurons, including thrombospondins, N-methyl-D-aspartate receptors, transient receptor potential ankyrin 1 (TRPA1), transient receptor potential vanilloid family 1 (TRPV1), and protein kinase C (PKC), are involved in neuropathic pain. Thus, we reviewed and discussed the role of Cavα2δ1 and the associated signaling axis in neuropathic pain conditions.

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.

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