Contribution of transient receptor potential vanilloid subfamily 1 to endothelin-1-induced thermal hyperalgesia

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.

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Antihyperalgesic effects of vanilloid-1 and bradykinin-1 receptor antagonists following spinal cord injury in rats

Journal of Neurosurgery Spine ◽

10.3171/spi.2007.6.5.420 ◽

2007 ◽

Vol 6 (5) ◽

pp. 420-424 ◽

Cited By ~ 18

Author(s):

Sharad Rajpal ◽

Tiffany A. Gerovac ◽

Nicholas A. Turner ◽

Jessica I. Tilghman ◽

Bradley K. Allcock ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Transient Receptor Potential ◽

Treatment Strategies ◽

Thermal Hyperalgesia ◽

Receptor Potential ◽

Transient Receptor Potential Vanilloid ◽

Cord Injury ◽

Bradykinin Antagonists ◽

Transient Receptor

Object The authors previously discovered that genes for the bradykinin-1 (B1) receptor and the transient receptor potential vanilloid subtype 1 (TRPV1) were overexpressed in animals exhibiting thermal hyperalgesia (TH) following spinal cord injury (SCI). They now report the effect of TRPV1 (AMG9810) and B1 (Lys-[Des-Arg9, Leu8]-bradykinin) antagonists on TH in animals following SCI. Methods The rats were subjected to contusion SCI and then divided into groups in which TH did or did not develop. The animals from both groups were given either AMG9810, Lys-(Des-Arg9, Leu8)-bradykinin, or the drug-specific vehicle (control groups). Animals were tested for TH preinjury and at regular intervals after SCI by using the hindlimb withdrawal latency test. Conclusions The administration of AMG9810 likely improves TH as a result of a generalized analgesic effect, whereas the effect of Lys-(Des-Arg9, Leu8)-bradykinin appears more specific to the reversal of TH. This information has potential usefulness in the development of treatment strategies for post-SCI neuropathic pain.

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

Neural Plasticity ◽

10.1155/2018/4861491 ◽

2018 ◽

Vol 2018 ◽

pp. 1-10 ◽

Cited By ~ 5

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms21124341 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4341 ◽

Cited By ~ 1

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.

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