scholarly journals Intrathecal Administration of AS1928370, a Transient Receptor Potential Vanilloid 1 Antagonist, Attenuates Mechanical Allodynia in a Mouse Model of Neuropathic Pain

2011 ◽  
Vol 34 (7) ◽  
pp. 1105-1108 ◽  
Author(s):  
Tomonari Watabiki ◽  
Tetsuo Kiso ◽  
Mina Tsukamoto ◽  
Toshiaki Aoki ◽  
Nobuya Matsuoka
Keyword(s):  
Neuropathic Pain ◽  
Mouse Model ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Intrathecal Administration ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

scholarly journals A Combined Water Extract of Frankincense and Myrrh Alleviates Neuropathic Pain in Mice via Modulation of TRPV1

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Danyou Hu ◽  
Changming Wang ◽  
Fengxian Li ◽  
Shulan Su ◽  
Niuniu Yang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Mouse Model ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Water Extract ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Nociceptive Response ◽  
Thermal Hypersensitivity

Frankincense and myrrh are widely used in clinics as a pair of herbs to obtain a synergistic effect for relieving pain. To illuminate the analgesia mechanism of frankincense and myrrh, we assessed its effect in a neuropathic pain mouse model. Transient receptor potential vanilloid 1 (TRPV1) plays a crucial role in neuropathic pain and influences the plasticity of neuronal connectivity. We hypothesized that the water extraction of frankincense and myrrh (WFM) exerted its analgesia effect by modulating the neuronal function of TRPV1. In our study, WFM was verified by UHPLC-TQ/MS assay. In vivo study showed that nociceptive response in mouse by heat and capsaicin induced were relieved by WFM treatment. Furthermore, thermal hypersensitivity and mechanical allodynia were also alleviated by WFM treatment in a chronic constriction injury (CCI) mouse model. CCI resulted in increased TRPV1 expression at both the mRNA and protein levels in predominantly small-to-medium neurons. However, after WFM treatment, TRPV1 expression was reverted in real-time PCR, Western blot, and immunofluorescence experiments. Calcium response to capsaicin was also decreased in cultured DRG neurons from CCI model mouse after WFM treatment. In conclusion, WFM alleviated CCI-induced mechanical allodynia and thermal hypersensitivity via modulating TRPV1.

scholarly journals Intrathecal Resiniferatoxin Modulates TRPV1 in DRG Neurons and Reduces TNF-Induced Pain-Related Behavior

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
M. Leo ◽  
M. Schulte ◽  
L.-I. Schmitt ◽  
M. Schäfers ◽  
C. Kleinschnitz ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Intrathecal Injection ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Intrathecal Administration ◽  
Transient Receptor Potential Vanilloid ◽  
Therapeutic Approaches ◽  
Transient Receptor

Transient receptor potential vanilloid-1 (TRPV1) is a nonselective cation channel, predominantly expressed in sensory neurons. TRPV1 is known to play an important role in the pathogenesis of inflammatory and neuropathic pain states. Previous studies suggest interactions between tumor necrosis factor- (TNF-) alpha and TRPV1, resulting in a modulation of ion channel function and protein expression in sensory neurons. We examined the effect of intrathecal administration of the ultrapotent TRPV1 agonist resiniferatoxin (RTX) on TNF-induced pain-associated behavior of rats using von Frey and hot plate behavioral testing. Intrathecal injection of TNF induces mechanical allodynia (2 and 20 ng/kg) and thermal hyperalgesia (200 ng) 24 h after administration. The additional intrathecal administration of RTX (1.9 μg/kg) alleviates TNF-induced mechanical allodynia and thermal hyperalgesia 24 h after injection. In addition, TNF increases the TRPV1 protein level and number of TRPV1-expressing neurons. Both effects could be abolished by the administration of RTX. These results suggest that the involvement of TRPV1 in TNF-induced pain offers new TRPV1-based experimental therapeutic approaches and demonstrates the analgesic potential of RTX in inflammatory pain diseases.

scholarly journals Paclitaxel Induces Upregulation of Transient Receptor Potential Vanilloid 1 Expression in the Rat Spinal Cord

2020 ◽  
Vol 21 (12) ◽  
pp. 4341 ◽  
Author(s):  
Yukako Kamata ◽  
Toshie Kambe ◽  
Terumasa Chiba ◽  
Ken Yamamoto ◽  
Kazuyoshi Kawakami ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Intrathecal Administration ◽  
Transient Receptor Potential Vanilloid ◽  
Rat Spinal Cord ◽  
Trpv1 Receptor ◽  
Transient Receptor

Painful peripheral neuropathy is a common adverse effect of paclitaxel (PTX) treatment. To analyze the contribution of transient receptor potential vanilloid 1 (TRPV1) in the development of PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia, TRPV1 expression in the rat spinal cord was analyzed after intraperitoneal administration of 2 and 4 mg/kg PTX. PTX treatment increased the expression of TRPV1 protein in the spinal cord. Immunohistochemistry showed that PTX (4 mg/kg) treatment increased TRPV1 protein expression in the superficial layers of the spinal dorsal horn 14 days after treatment. Behavioral assessment using the paw withdrawal response showed that PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia after 14 days was significantly inhibited by oral or intrathecal administration of the TRPV1 antagonist AMG9810. We found that intrathecal administration of small interfering RNA (siRNA) to knock down TRPV1 protein expression in the spinal cord significantly decreased PTX-induced mechanical allodynia/hyperalgesia and thermal hyperalgesia. Together, these results demonstrate that TRPV1 receptor expression in spinal cord contributes, at least in part, to the development of PTX-induced painful peripheral neuropathy. TRPV1 receptor antagonists may be useful in the prevention and treatment of PTX-induced peripheral neuropathic pain.

scholarly journals JI017 Attenuates Oxaliplatin-Induced Cold Allodynia via Spinal TRPV1 and Astrocytes Inhibition in Mice

2021 ◽  
Vol 22 (16) ◽  
pp. 8811
Author(s):  
Ji Hwan Lee ◽  
Hyunseung Ji ◽  
Seong-Gyu Ko ◽  
Woojin Kim
Keyword(s):  
Neuropathic Pain ◽  
Dorsal Horn ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Zingiber Officinale ◽  
Pcr Analysis ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Antagonist ◽  
Transient Receptor

Oxaliplatin, a well-known chemotherapeutic agent, can induce severe neuropathic pain, which can seriously decrease the quality of life of patients. JI017 is an herb mixture composed of Aconitum carmichaelii, Angelica gigas, and Zingiber officinale. Its anti-tumor effect has been reported; however, the efficacy of JI017 against oxaliplatin-induced allodynia has never been explored. Single oxaliplatin injection [6 mg/kg, intraperitoneal, (i.p.)] induced both cold and mechanical allodynia, and oral administration of JI017 (500 mg/kg) alleviated cold but not mechanical allodynia in mice. Real-time polymerase chain reaction (PCR) analysis demonstrated that the upregulation of mRNA of spinal transient receptor potential vanilloid 1 (TRPV1) and astrocytes following oxaliplatin injection was downregulated after JI017 treatment. Moreover, TRPV1 expression and the activation of astrocytes were intensely increased in the superficial area of the spinal dorsal horn after oxaliplatin treatment, whereas JI017 suppressed both. The administration of TRPV1 antagonist [capsazepine, intrathecal (i.t.), 10 μg] attenuated the activation of astrocytes in the dorsal horn, demonstrating that the functions of spinal TRPV1 and astrocytes are closely related in oxaliplatin-induced neuropathic pain. Altogether, these results suggest that JI017 may be a potent candidate for the management of oxaliplatin-induced neuropathy as it decreases pain, spinal TRPV1, and astrocyte activation.

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 Periorbital nociception in a progressive multiple sclerosis mouse model is dependent on TRPA1 channel activation

2021 ◽  
Author(s):  
Diéssica Padilha Dalenogare ◽  
Diulle Spat Peres ◽  
Maria Fernanda Pessano Fialho ◽  
Gabriela Trevisan dos Santos
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Progressive Multiple Sclerosis ◽  
Autoimmune Encephalomyelitis ◽  
Transient Receptor ◽  
Multiple Sclerosis Patients ◽  
Santa Maria

Background: Headache is one of the main painful symptoms described by multiple sclerosis patients. Previously, it was described that neuropathic pain-like behaviors were dependent on transient receptor potential ankyrin 1 (TRPA1) activation in a progressive multiple sclerosis model induced by experimental autoimmune encephalomyelitis (PMS- EAE) in mice. Objective: Here, we aimed to investigate if periorbital mechanical allodynia induced by PMS-EAE was also related to TRPA1 activation. Design and setting: Federal University of Santa Maria, Santa Maria, RS, Brazil. Methods: To induce a PMS-EAE we used female C57BL/6 wild-type and TRPA1- deficient (Trpa1-/-) mice. By the von Frey test, periorbital mechanical allodynia development was observed, and the nociception peak occurred 14 days after induction. At nociception peak day, the mice were treated with sumatriptan, TRPA1 antagonists (HC-030031, A-967079, metamizole, and propyphenazone. Results: The development of mechanical allodynia was showed as well as the antinociceptive effects for all treatments in induced mice. A significant reduction of TRPA1 expression was detected. Conclusion: Thus, these results suggest that headache-like symptoms induced by the PMS-EAE mouse model might occurring by TRPA1 activation.

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.

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