Diacerein reduces joint damage, pain behavior and inhibits transient receptor potential vanilloid 1, matrix metalloproteinase and glial cells in rat spinal cord

2015 ◽  
Vol 20 (10) ◽  
pp. 1337-1349 ◽  
Author(s):  
Morgana Duarte da Silva ◽  
Francisco José Cidral-Filho ◽  
Elisa Cristina Winkelmann-Duarte ◽  
Eduardo Cargnin-Ferreira ◽  
João B. Calixto ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Matrix Metalloproteinase ◽  
Glial Cells ◽  
Transient Receptor Potential ◽  
Joint Damage ◽  
Receptor Potential ◽  
Pain Behavior ◽  
Transient Receptor Potential Vanilloid ◽  
Rat Spinal Cord ◽  
Transient Receptor

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 Transient receptor potential vanilloid 1-immunoreactive signals in murine enteric glial cells

2016 ◽  
Vol 22 (44) ◽  
pp. 9752 ◽  
Author(s):  
Masahiro Yamamoto ◽  
Mitsue Nishiyama ◽  
Seiichi Iizuka ◽  
Shigeaki Suzuki ◽  
Norihiro Suzuki ◽  
...  
Keyword(s):  
Glial Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Enteric Glial Cells ◽  
Transient Receptor

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

2007 ◽  
Vol 6 (5) ◽  
pp. 420-424 ◽  
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.

scholarly journals Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain

2021 ◽  
Vol 22 (11) ◽  
pp. 6084
Author(s):  
Adnan Khan ◽  
Bushra Shal ◽  
Ashraf Ullah Khan ◽  
Rahim Ullah ◽  
Muhammad Waleed Baig ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Transient Receptor Potential ◽  
Purinergic Receptor ◽  
Receptor Potential ◽  
B Cell Lymphoma ◽  
Mapk Signaling ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

Vincristine (VCR) is a widely used chemotherapy drug that induced peripheral painful neuropathy. Yet, it still lacks an ideal therapeutic strategy. The transient receptor potential (TRP) channels, purinergic receptor (P2Y), and mitogen-activated protein kinase (MAPK) signaling play a crucial role in the pathogenesis of neuropathic pain. Withametelin (WMT), a potential Phytosteroid isolated from datura innoxa, exhibits remarkable neuroprotective properties. The present investigation was designed to explore the effect of withametelin on VCR-induced neuropathic pain and its underlying molecular mechanism. Initially, the neuroprotective potential of WMT was confirmed against hydrogen peroxide (H2O2)-induced PC12 cells. To develop potential candidates for neuropathic pain treatment, a VCR-induced neuropathic pain model was established. Vincristine (75 μg/kg) was administered intraperitoneally (i.p.) for 10 consecutive days (day 1–10) for the induction of neuropathic pain. Gabapentin (GBP) (60 mg/kg, i.p.) and withametelin (0.1 and 1 mg/kg i.p.) treatments were given after the completion of VCR injection on the 11th day up to 21 days. The results revealed that WMT significantly reduced VCR-induced pain hypersensitivity, including mechanical allodynia, cold allodynia, and thermal hyperalgesia. It reversed the VCR-induced histopathological changes in the brain, spinal cord, and sciatic nerve. It inhibited VCR-induced changes in the biochemical composition of the myelin sheath of the sciatic nerve. It markedly downregulated the expression levels of TRPV1 (transient receptor potential vanilloid 1); TRPM8 (Transient receptor potential melastatin 8); and P2Y nociceptors and MAPKs signaling, including ERK (Extracellular Signal-Regulated Kinase), JNK (c-Jun N-terminal kinase), and p-38 in the spinal cord. It suppressed apoptosis by regulating Bax (Bcl2-associated X-protein), Bcl-2 (B-cell-lymphoma-2), and Caspase-3 expression. It considerably attenuated inflammatory cytokines, oxidative stress, and genotoxicity. This study suggests that WMT treatment suppressed vincristine-induced neuropathic pain by targeting the TRPV1/TRPM8/P2Y nociceptors and MAPK signaling.

scholarly journals Update on the Role of Spinal Cord TRPV1 Receptors in Pain Modulation

2014 ◽  
pp. S225-S236 ◽  
Author(s):  
D. SPICAROVA ◽  
V. NERANDZIC ◽  
J. PALECEK
Keyword(s):  
Spinal Cord ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Short Review ◽  
Pain Modulation ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv1 Receptors ◽  
Transient Receptor ◽  
And Function

The structure, expression and function of the transient receptor potential vanilloid 1 (TRPV1) receptor were intensively studied since the cloning in 1997 and TRPV1 receptors are now considered to act as transducers and molecular integrators of nociceptive stimuli in the periphery. In contrast, spinal TRPV1 receptors were studied less extensively and their role in pain modulation is still not fully understood. This short review is a follow up on our previous summary in this area (Spicarova and Palecek 2008). The aim was to review preferentially the most recent findings concerning the role of the spinal TRPV1 receptors, published within the last five years. The update is given on the expression and function of the spinal TRPV1 receptors, their activation by endogenous agonists, interaction between the endocannabinoid and endovanillod system and possible role of the spinal TRPV1 receptors in pathological pain states. There is now mounting evidence that TRPV1 receptors may be an important element in modulation of nociceptive information at the spinal cord level and represent an interesting target for analgesic therapy.

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