scholarly journals Antioxidative and Analgesic Effects of Naringin through Selective Inhibition of Transient Receptor Potential Vanilloid Member 1

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 64
Author(s):  
Sanung Eom ◽  
Bo-Bae Lee ◽  
Shinhui Lee ◽  
Youngseo Park ◽  
Hye Duck Yeom ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Selective Inhibition ◽  
Transient Receptor Potential Vanilloid ◽  
Amino Acid Residues ◽  
Suppression Effect ◽  
Analgesic Effects ◽  
Inward Currents ◽  
Transient Receptor

Transient receptor potential vanilloid member 1 (TRPV1) is activated in response to capsaicin, protons, temperature, and free reactive oxygen species (ROS) released from inflammatory molecules after exposure to harmful stimuli. The expression level of TRPV1 is elevated in the dorsal root ganglion, and its activation through capsaicin and ROS mediates neuropathic pain in mice. Its expression is high in peripheral and central nervous systems. Although pain is a response evolved for survival, many studies have been conducted to develop analgesics, but no clear results have been reported. Here, we found that naringin selectively inhibited capsaicin-stimulated inward currents in Xenopus oocytes using a two-electrode voltage clamp. The results of this study showed that naringin has an IC50 value of 33.3 μM on TRPV1. The amino acid residues D471 and N628 of TRPV1 were involved in its binding to naringin. Our study bridged the gap between the pain suppression effect of TRPV1 and the preventive effect of naringin on neuropathic pain and oxidation. Naringin had the same characteristics as a model selective antagonist, which is claimed to be ideal for the development of analgesics targeting TRPV1. Thus, this study suggests the applicability of naringin as a novel analgesic candidate through antioxidative and analgesic effects of naringin.

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 Structure-based characterization of novel TRPV5 inhibitors

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Taylor ET Hughes ◽  
John Smith Del Rosario ◽  
Abhijeet Kapoor ◽  
Aysenur Torun Yazici ◽  
Yevgen Yudin ◽  
...  
Keyword(s):  
Rational Design ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Parent Compound ◽  
Specific Inhibitor ◽  
Receptor Potential ◽  
Selective Inhibition ◽  
Transient Receptor Potential Vanilloid ◽  
Calcium Reabsorption ◽  
Transient Receptor

Transient receptor potential vanilloid 5 (TRPV5) is a highly calcium selective ion channel that acts as the rate-limiting step of calcium reabsorption in the kidney. The lack of potent, specific modulators of TRPV5 has limited the ability to probe the contribution of TRPV5 in disease phenotypes such as hypercalcemia and nephrolithiasis. Here, we performed structure-based virtual screening (SBVS) at a previously identified TRPV5 inhibitor binding site coupled with electrophysiology screening and identified three novel inhibitors of TRPV5, one of which exhibits high affinity, and specificity for TRPV5 over other TRP channels, including its close homologue TRPV6. Cryo-electron microscopy of TRPV5 in the presence of the specific inhibitor and its parent compound revealed novel binding sites for this channel. Structural and functional analysis have allowed us to suggest a mechanism of action for the selective inhibition of TRPV5 and lay the groundwork for rational design of new classes of TRPV5 modulators.

Repeated capsaicin patch applications in patients with localized peripheral neuropathic pain

Ból ◽  
2021 ◽  
Vol 22 (1) ◽  
pp. 56-65
Author(s):  
Małgorzata Malec-Milewska ◽  
Jerzy Wordliczek ◽  
Renata Zajączkowska
Keyword(s):  
Neuropathic Pain ◽  
Transient Receptor Potential ◽  
Significant Proportion ◽  
Case Series ◽  
Receptor Potential ◽  
The Body ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor ◽  
Good Treatment Option ◽  
Localized Neuropathic Pain

Neuropathic pain is still a challenging problem. It is experienced by millions of people worldwide, with an approximate prevalence of 7‒10% in the general population. Despite the availability of a variety of treatment methods, a significant proportion of patients suffer from poorly controlled neuropathic pain. Capsaicin is a highly selective TRPV1 (Transient Receptor Potential Vanilloid Type 1) agonist. When applied topically, it leads to the defunctionalisation of hyperactive nociceptive receptors, temporary destruction of peripheral nerve endings, and a significant reduction or cessation of pain. Therefore 8% capsaicin patches are used to treat several peripheral, localized neuropathic pain syndromes. The study aimed to present a case series of patients suffering from peripheral, localized neuropathic pain in case the use of repeated applications of 8% capsaicin patches significantly reduced the intensity of pain. In 5 out of 6 patients we observed a gradual extension of the pain relief period until the pain disappeared, which led to the reduction or discontinuation of systemic pharmacotherapy. In summary, a therapy limited to a certain area of the body, without potential systemic adverse effects, which requires repetition at fairly long intervals, appears to be a good treatment option.

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