scholarly journals Pirt Together with TRPV1 Is Involved in the Regulation of Neuropathic Pain

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Changming Wang ◽  
Leying Gu ◽  
Yonglan Ruan ◽  
Tana Gegen ◽  
Lei Yu ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Transient Receptor Potential ◽  
Life Quality ◽  
Thermal Hyperalgesia ◽  
In Vitro Study ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Cci Model ◽  
Transient Receptor

Neuropathic pain is a chronic pain and reduces the life quality of patients substantially. Transient receptor potential vanilloid channel 1 (TRPV1), a nonselective cation channel, has been shown to play a crucial role in neuropathic pain. Although TRPV1 plays an important role in neuropathic pain, the mechanism of how TRPV1 was regulated in neuropathic pain remains unclear. Pirt is a membrane protein and binds to TRPV1 to enhance its activity. It was suggested that Pirt should also be involved in neuropathic pain. In this study, we investigated the role of Pirt in neuropathic pain (CCI model); the results show that mechanical allodynia and thermal hyperalgesia were alleviated in Pirt−/− mice in CCI models. TRPV1 expression was increased by immunofluorescence and real-time PCR experiments. The increase in TRPV1 expression was less in Pirt knockout mice in CCI models. Moreover, the number of capsaicin-responding neurons and the magnitude of evoked calcium response were attenuated in DRG neurons from Pirt−/− mice in CCI models. Finally, we found that the pain behavior attenuated in dysfunction of both Pirt and TRPV1 was much stronger than in dysfunction of Pirt or TRPV1 only in a CCI model in vitro study. Taken together, Pirt together with TRPV1 is involved in CCI-induced neuropathic pain.

scholarly journals The mechanisms of protease-activated receptor 2 in mediating pain behaviors through nonselective cation channel signaling

2020 ◽  
Author(s):  
Yaping Yue ◽  
Na Wang ◽  
Yanming Lau ◽  
Yiran Fu ◽  
Hao Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Drg Neurons ◽  
Pain Behaviors ◽  
Transient Receptor

Abstract Background: Activation of purinergic receptor P2X ligand-gated ion channel 3 (P2X3), transient receptor potential vanilloid type 1 (TRPV1), and transient receptor potential ankyrin 1 (TRPA1) by their specific ligands is a major mechanism contributing to magnified pain responses. The relationship between these nonselective cation channels and proteinase-activated receptor 2 (PAR2) activation mediated pain is still to be clarified.Methods: In this study, both in vitro model of dorsal root ganglion (DRG) neurons with PAR2 agonist SL-NH2 challenge and SL-NH2-induced pain rat model were used to approach these questions. The expression of P2X3, TRPV1, and TRPA1 in DRG neurons was investigated by quantitative real-time RT-PCR, Western blot, and immunofluorescence. The involvement of the PLCβ3/PKCε signaling pathway was also determined. The behavior test for mechanical allodynia and thermal hyperalgesia was performed. Results: SL-NH2 induced upregulation of P2X3, TRPV1, and TRPA1 through phosphorylation of phospholipase Cβ3 (PLCβ3) and protein kinase Cε (PKCε) signaling pathway in DRG neurons in vitro and in vivo. SL-NH2 also elevated the proportion of P2X3-, TRPV1-, and TRPA1-expressing neurons. The upregulation of P2X3, TRPV1, and TRPA1 and phosphorylation of PLCβ3 and PKCε in DRG neurons was paralleled with mechanical allodynia and thermal hyperalgesia behaviors in rats. Conclusions: The data of the present study imply that SL-NH2 as a noxious stimulus activates PAR2 which induces TRPV1, TRPA1, and P2X3 upregulation through PLCβ3/PKCε signaling pathway, thereby decreasing activation thresholds and increasing excitability, resulting in sustained nociceptive activity in DRG neurons, and then causing mechanical allodynia and thermal hyperalgesia behaviors. These data expanded our knowledge about PAR2-mediated pain sensitivity and its relationship with TRPV1, TRPA1, and P2X3 and provided new opportunities on management of pain behaviors.

scholarly journals Lipid Nanoparticle Inclusion Prevents Capsaicin-Induced TRPV1 Defunctionalization

Pharmaceutics ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 339
Author(s):  
Carmelo Puglia ◽  
Debora Santonocito ◽  
Angela Bonaccorso ◽  
Teresa Musumeci ◽  
Barbara Ruozi ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Prolonged Exposure ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Spontaneous Pain ◽  
Plantar Surface ◽  
Transient Receptor ◽  
Chronic Pain Conditions

Background: Capsaicin (CPS) is a highly selective agonist of the transient receptor potential vanilloid type 1 (TRPV1) with a nanomolar affinity. High doses or prolonged exposure to CPS induces TRPV1 defunctionalization and, although this effect is currently used for the treatment of thermal hyperalgesia in chronic pain conditions, it is responsible of detrimental effects, such as denervation of sensory fibers. The aim of the present study was to formulate CPS loaded lipid nanocarriers (CPS-LN) in order to optimize CPS release, thus preventing TRPV1 internalization and degradation. Methods: CPS-LNs were formulated and characterized by in vitro studies. The activation of TRPV1 receptors after CPS-LN administration was evaluated by measuring spontaneous pain that was induced by local injection into the plantar surface of the mouse hind-paw. Moreover, the expression of TRPV1 in the skin was evaluated by western blot analysis in CPS-LN injected mice and then compared to a standard CPS solution (CPS-STD). Results: CPS inclusion in LN induced a lower pain response when compared to CPS-STD; further, it prevented TRPV1 down-regulation in the skin, while CPS-STD induced a significant reduction of TRPV1 expression. Conclusions: Drug encapsulation in lipid nanoparticles produced an optimization of CPS release, thus reducing mice pain behavior and avoiding the effects that are caused by TRPV1 defunctionalization related to a prolonged activation of this receptor.

scholarly journals MZF1 in the Dorsal Root Ganglia Contributes to the Development and Maintenance of Neuropathic Pain via Regulation of TRPV1

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Fei Xing ◽  
Hanwen Gu ◽  
Qin Niu ◽  
Xiaochong Fan ◽  
Zhongyu Wang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Zinc Finger ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Withdrawal Threshold ◽  
Lumbar Level ◽  
Transient Receptor

Previous studies have demonstrated that myeloid zinc finger 1 (MZF1) in the dorsal root ganglion (DRG) participates in neuropathic pain induced by chronic-constriction injury (CCI) via regulation of voltage-gated K+ channels (Kv). Emerging evidence indicates that transient receptor potential vanilloid 1 (TRPV1) is involved in the development and maintenance of neuropathic pain. Although it is known that the transcription of TRPV1 is regulated by Kruppel-like zinc-finger transcription factor 7 (Klf7)—and that the structure of TRPV1 is similar to that of Kv—few studies have systematically investigated the relationship between MZF1 and TRPV1 in neuropathic pain. In the present study, we demonstrated that CCI induced an increase in MZF1 and TRPV1 in lumbar-level 4/5 (L4/5) DRGs at 3 days post-CCI and that this increase was persistent until at least 14 days post-CCI. DRG microinjection of rAAV5-MZF1 into the DRGs of naïve rats resulted in a decrease in paw-withdrawal threshold (PWT) and paw-withdrawal latency (PWL) compared with that of the rAAV5-EGFP group, which started at four weeks and lasted until at least eight weeks after microinjection. Additionally, prior microinjection of MZF1 siRNA clearly ameliorated CCI-induced reduction in PWT and PWL at 3 days post-CCI and lasted until at least 7 days post-CCI. Correspondingly, microinjection of MZF1 siRNA subsequent to CCI alleviated the established mechanical allodynia and thermal hyperalgesia induced by CCI, which occurred at 3 days postinjection and lasted until at least 10 days postinjection. Microinjection of rAAV5-MZF1 increased the expression of TRPV1 in DRGs. Microinjection of MZF1 siRNA diminished the CCI-induced increase of TRPV1, but not P2X7R, in DRGs. These findings suggest that MZF1 may contribute to neuropathic pain via regulation of TRPV1 expression in DRGs.

scholarly journals Novel role of transient receptor potential vanilloid 2 in the regulation of cardiac performance

2014 ◽  
Vol 306 (4) ◽  
pp. H574-H584 ◽  
Author(s):  
Jack Rubinstein ◽  
Valerie M. Lasko ◽  
Sheryl E. Koch ◽  
Vivek P. Singh ◽  
Vinicius Carreira ◽  
...  
Keyword(s):  
Vascular Function ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Wild Type ◽  
Transient Receptor ◽  
Systolic And Diastolic Function ◽  
Myocyte Contractility

Transient receptor potential cation channels have been implicated in the regulation of cardiovascular function, but only recently has our laboratory described the vanilloid-2 subtype (TRPV2) in the cardiomyocyte, though its exact mechanism of action has not yet been established. This study tests the hypothesis that TRPV2 plays an important role in regulating myocyte contractility under physiological conditions. Therefore, we measured cardiac and vascular function in wild-type and TRPV2−/− mice in vitro and in vivo and found that TRPV2 deletion resulted in a decrease in basal systolic and diastolic function without affecting loading conditions or vascular tone. TRPV2 stimulation with probenecid, a relatively selective TRPV2 agonist, caused an increase in both inotropy and lusitropy in wild-type mice that was blunted in TRPV2−/− mice. We examined the mechanism of TRPV2 inotropy/lusitropy in isolated myocytes and found that it modulates Ca2+ transients and sarcoplasmic reticulum Ca2+ loading. We show that the activity of this channel is necessary for normal cardiac function and that there is increased contractility in response to agonism of TRPV2 with probenecid.

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