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 Periorbital Nociception in a Progressive Multiple Sclerosis Mouse Model is Dependent on TRPA1 Channel Activation

2021 ◽  
Vol 14 (8) ◽  
pp. 831
Author(s):  
Diéssica Padilha Dalenogare ◽  
Camila Ritter ◽  
Fernando Roberto Antunes Bellinaso ◽  
Sabrina Qader Kudsi ◽  
Gabriele Cheiran Pereira ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Nadph Oxidase ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Progressive Multiple Sclerosis ◽  
Oxidase Inhibitor ◽  
Autoimmune Encephalomyelitis ◽  
Transient Receptor

Headaches are frequently described in progressive multiple sclerosis (PMS) patients, but their mechanism remains unknown. Transient receptor potential ankyrin 1 (TRPA1) was involved in neuropathic nociception in a model of PMS induced by experimental autoimmune encephalomyelitis (PMS-EAE), and TRPA1 activation causes periorbital and facial nociception. Thus, our purpose was to observe the development of periorbital mechanical allodynia (PMA) in a PMS-EAE model and evaluate the role of TRPA1 in periorbital nociception. Female PMS-EAE mice elicited PMA from day 7 to 14 days after induction. The antimigraine agents olcegepant and sumatriptan were able to reduce PMA. The PMA was diminished by the TRPA1 antagonists HC-030031, A-967079, metamizole and propyphenazone and was absent in TRPA1-deficient mice. Enhanced levels of TRPA1 endogenous agonists and NADPH oxidase activity were detected in the trigeminal ganglion of PMS-EAE mice. The administration of the anti-oxidants apocynin (an NADPH oxidase inhibitor) or alpha-lipoic acid (a sequestrant of reactive oxygen species), resulted in PMA reduction. These results suggest that generation of TRPA1 endogenous agonists in the PMS-EAE mouse model may sensitise TRPA1 in trigeminal nociceptors to elicit PMA. Thus, this ion channel could be a potential therapeutic target for the treatment of headache in PMS patients.

scholarly journals Transient Receptor Potential Vanilloid 1 Modulates Central Inflammation in Multiple Sclerosis

2019 ◽  
Vol 10 ◽  
Author(s):  
Mario Stampanoni Bassi ◽  
Antonietta Gentile ◽  
Ennio Iezzi ◽  
Sara Zagaglia ◽  
Alessandra Musella ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
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 Carboplatin Enhances the Activity of Human Transient Receptor Potential Ankyrin 1 through the Cyclic AMP-Protein Kinase A-A-Kinase Anchoring Protein (AKAP) Pathways

2019 ◽  
Author(s):  
Kanako Miyano ◽  
Seiji Shiraishi ◽  
Koichiro Minami ◽  
Yuka Sudo ◽  
Masami Suzuki ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Mechanical Allodynia ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Adenosine Monophosphate ◽  
Anchoring Protein ◽  
Cold Hyperalgesia ◽  
Transient Receptor ◽  
Kinase A

Carboplatin, an anticancer drug, often causes chemotherapy-induced peripheral neuropathy (PN). Transient receptor potential ankyrin 1 (TRPA1), a non-selective cation channel, is a polymodal nociceptor expressed in sensory neurons. TRPA1 is involved not only in pain transmission but also in allodynia or hyperalgesia development. However, the effects of TRPA1 on carboplatin-induced PN is unclear. We revealed that carboplatin induced mechanical allodynia and cold hyperalgesia, and the pains observed in carboplatin-induced PN models were significantly suppressed by the TRPA1 antagonist HC-030031 without a change in the level of TRPA1 protein. In cells expressing human TRPA, carboplatin had no effects on changes in intracellular Ca2+ concentration ([Ca2+]i); however, carboplatin pretreatment enhanced the increase in [Ca2+]i induced by the TRPA1 agonist, allyl isothiocyanate (AITC). These effects were suppressed by an inhibitor of protein kinase A (PKA). The PKA activator forskolin enhanced AITC-induced increase in [Ca2+]i and carboplatin itself increased intracellular cyclic adenosine monophosphate (cAMP) levels. Moreover, inhibition of A-kinase anchoring protein (AKAP) significantly decreased carboplatin-induced enhancement of [Ca2+]i induced by AITC and improved carboplatin-induced mechanical allodynia and cold hyperalgesia. These results suggested that carboplatin induced mechanical allodynia and cold hyperalgesia by increasing sensitivity to TRPA1 via the cAMP-PKA-AKAP pathway.

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