Glial Activation Enhances Spinal TRPV1 Receptor Sensitivity in a Paclitaxel Model of Neuropathic Pain

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F25%3A00639090" target="_blank" >RIV/67985823:_____/25:00639090 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11310/25:10502545

Result on the web

<a href="https://www.biomed.cas.cz/physiolres/pdf/2025/74_677.pdf" target="_blank" >https://www.biomed.cas.cz/physiolres/pdf/2025/74_677.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.33549/physiolres.935599" target="_blank" >10.33549/physiolres.935599</a>

Result language

angličtina

Original language name

Glial Activation Enhances Spinal TRPV1 Receptor Sensitivity in a Paclitaxel Model of Neuropathic Pain

Original language description

Paclitaxel (PTX), a commonly used chemotherapeutic, frequently leads to chemotherapy-induced peripheral neuropathy (CIPN), characterized by persistent pain and neuronal hypersensitivity. While its effects on peripheral nerves are well-documented, paclitaxel also influences central nervous system pathways, particularly spinal synaptic transmission, through Toll-like receptor 4 (TLR4) activation and subsequent sensitization of transient receptor potential vanilloid 1 (TRPV1) receptors. In this study, we used an in vitro model of paclitaxel-induced neuropathic pain to investigate the role of glial activation in TRPV1 receptor function. Using whole-cell patch-clamp recordings from superficial dorsal horn neurons in acute spinal cord slices, we evaluated the effects of minocycline (MX), a glial cell inhibitor, and ISO-1, a macrophage migration inhibitory factor (MIF) antagonist, on paclitaxel-induced synaptic changes. Our results demonstrate that acute paclitaxel application enhances nociceptive signaling and impairs capsaicininduced TRPV1 receptor tachyphylaxis, leading to sustained hyperactivity. Minocycline preincubation effectively mitigated paclitaxel-induced sensitization, restoring normal nociceptive signaling, whereas acute minocycline treatment failed to prevent these changes. ISO-1 in vitro co-incubation with paclitaxel did not affect the paclitaxel-induced changes. These findings offer novel insight into the intricate interactions among neuroinflammatory mediators, glial cell activation, and TRPV1 receptor sensitization in paclitaxel-induced neuropathic pain. The differential effects of acute versus prolonged pre-incubation minocycline application suggest the importance of sustained glial inhibition for effective outcomes and neuropathic pain management.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30103 - Neurosciences (including psychophysiology)

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2025

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Physiological Research

ISSN

0862-8408

e-ISSN

1802-9973

Volume of the periodical

74

Issue of the periodical within the volume

4

Country of publishing house

CZ - CZECH REPUBLIC

Number of pages

15

Pages from-to

677-691

UT code for WoS article

001568778000014

EID of the result in the Scopus database

2-s2.0-105015121370