Meteorin Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Mice

Sankaranarayanan, Ishwarya; Ferreira, Diana Tavares; He, Lucy; Kume, Moeno; Mwirigi, Juliet; Madsén, Torsten; Petersen, KA; Munro, Gordon; Price, Theodore J.

doi:10.1016/j.jpain.2022.10.015

Cited by 7 publications

(2 citation statements)

References 48 publications

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“…As mentioned above, one testable hypothesis is satellite cell gliosis which is well known to occur in CIPN mouse models. Interestingly we recently showed that meteorin, which is thought to target satellite glial cells, can both prevent and reverse paclitaxel-evoked pain and signs of neuropathy 77 .…”

Section: Discussionmentioning

confidence: 99%

Protease-Activated Receptor 2 (PAR2) expressed in sensory neurons contributes to signs of pain and neuropathy in paclitaxel treated mice

Kume

Ahmad

DeFea³

et al. 2023

Preprint

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Background and Purpose: Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common, dose-limiting side effect of cancer therapy. Protease-activated receptor 2 (PAR2) is implicated in a variety of pathologies, including CIPN. In this study, we demonstrate the role of PAR2 expressed in sensory neurons in a paclitaxel (PTX)-induced model of CIPN in mice. Experimental Approach: CIPN was induced in both PAR2 knockout/WT mice and mice with PAR2 ablated in sensory neurons via the intraperitoneal injection of paclitaxel. In vivo behavioral studies were done in mice using von Frey filaments and the Mouse Grimace Scale. We then examined immunohistochemical staining of dorsal root ganglion (DRG) and hind paw skin samples from CIPN mice to measure satellite cell gliosis and intra-epidermal nerve fiber (IENF) density. Pharmacological reversal of CIPN pain was tested with the PAR2 antagonist C781 Key Results: Mechanical allodynia caused by paclitaxel treatment was alleviated in PAR2 knockout mice of both sexes. In the PAR2 sensory neuronal conditional knockout (cKO) mice, both mechanical allodynia and facial grimacing were attenuated in mice of both sexes. In the dorsal root ganglion of the paclitaxel-treated PAR2 cKO mice, satellite glial cell activation was reduced compared to control mice. IENF density analysis of the skin showed that the paclitaxel-treated control mice have a reduction in nerve fiber density while the PAR2 cKO mice had a comparable skin innervation as the vehicle-treated animals. Similar results were seen with satellite cell gliosis in the DRG where gliosis induced by PTX was absent in PAR cKO mice. Finally, C781 was able to transiently reverse established PTX-evoked mechanical allodynia. Conclusions and Implications: Our work demonstrates that PAR2 expressed in sensory neurons plays a key role in paclitaxel-induced mechanical allodynia, spontaneous pain and signs of neuropathy, suggesting PAR2 as a possible therapeutic target in multiple aspects of paclitaxel CIPN.

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Section: Discussionmentioning

confidence: 99%

Protease-Activated Receptor 2 (PAR2) expressed in sensory neurons contributes to signs of pain and neuropathy in paclitaxel treated mice

Kume

Ahmad

DeFea³

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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“…In mice and rats paclitaxel, a taxane derivative, induces CIPN with hypersensitivity to mechanical and thermal stimuli. Hence, its application to rodents is one of several wellestablished methods to investigate analgesic, antiallodynic and antihyperalgesic properties of drug candidates able to attenuate neuropathic pain in the course of CIPN [51,52]. The mechanisms underlying paclitaxel-induced cytotoxicity to sensory nerves are complex and they comprise, inter alia, altered opioidergic neurotransmission signaling [53,54], oxidative stress-induced mitochondrial damage, dysregulated calcium homeostasis, neuroinflammation, as well as changed neuronal excitability due to overexpressed voltage-gated ion (calcium and sodium) channels [41,55,56].…”

Section: Discussionmentioning

confidence: 99%

Naturally Inspired Molecules for Neuropathic Pain Inhibition—Effect of Mirogabalin and Cebranopadol on Mechanical and Thermal Nociceptive Threshold in Mice

Sałat,

Zaręba,

Awtoniuk

et al. 2023

Molecules

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Background: Neuropathic pain is drug-resistant to available analgesics and therefore novel treatment options for this debilitating clinical condition are urgently needed. Recently, two drug candidates, namely mirogabalin and cebranopadol have become a subject of interest because of their potential utility as analgesics for chronic pain treatment. However, they have not been investigated thoroughly in some types of neuropathic pain, both in humans and experimental animals. Methods: This study used the von Frey test, the hot plate test and the two-plate thermal place preference test supported by image analysis and machine learning to assess the effect of intraperitoneal mirogabalin and subcutaneous cebranopadol on mechanical and thermal nociceptive threshold in mouse models of neuropathic pain induced by streptozotocin, paclitaxel and oxaliplatin. Results: Mirogabalin and cebranopadol effectively attenuated tactile allodynia in models of neuropathic pain induced by streptozotocin and paclitaxel. Cebranopadol was more effective than mirogabalin in this respect. Both drugs also elevated the heat nociceptive threshold in mice. In the oxaliplatin model, cebranopadol and mirogabalin reduced cold-exacerbated pain. Conclusions: Since mirogabalin and cebranopadol are effective in animal models of neuropathic pain, they seem to be promising novel therapies for various types of neuropathic pain in patients, in particular those who are resistant to available analgesics.

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A pan-cancer analysis of the association of METRN with prognosis and immune infiltration in human tumors

Wang,

Huang,

Xiao

et al. 2024

Heliyon

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Meteorin Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Mice

Cited by 7 publications

References 48 publications

Protease-Activated Receptor 2 (PAR2) expressed in sensory neurons contributes to signs of pain and neuropathy in paclitaxel treated mice

Protease-Activated Receptor 2 (PAR2) expressed in sensory neurons contributes to signs of pain and neuropathy in paclitaxel treated mice

Naturally Inspired Molecules for Neuropathic Pain Inhibition—Effect of Mirogabalin and Cebranopadol on Mechanical and Thermal Nociceptive Threshold in Mice

A pan-cancer analysis of the association of METRN with prognosis and immune infiltration in human tumors

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