SGIP1 Deletion in Mice Attenuates Mechanical Hypersensitivity Elicited by Inflammation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60461373%3A22330%2F24%3A43930144" target="_blank" >RIV/60461373:22330/24:43930144 - isvavai.cz</a>

Result on the web

<a href="https://www.liebertpub.com/doi/10.1089/can.2024.0020?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed" target="_blank" >https://www.liebertpub.com/doi/10.1089/can.2024.0020?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1089/can.2024.0020" target="_blank" >10.1089/can.2024.0020</a>

Result language

angličtina

Original language name

SGIP1 Deletion in Mice Attenuates Mechanical Hypersensitivity Elicited by Inflammation

Original language description

Background: Activation of cannabinoid receptor 1 (CB1R) in the nervous system modulates the processing of acute and chronic pain. CB1R activity is regulated by desensitization and internalization. SH3-containing GRB2-like protein 3-interacting protein 1 (SGIP1) inhibits the internalization of CB1R. This causes increased and prolonged association of the desensitized receptor with G protein-coupled receptor kinase 3 (GRK3) and beta-arrestin on the cell membrane and results in decreased activation of extracellular signal-regulated kinase 1/2 (ERK1/2) pathway. Genetic deletion of SGIP1 in mice leads to altered CB1R-related functions, such as decreased anxiety-like behaviors, modified cannabinoid tetrad behaviors, reduced acute nociception, and increased sensitivity to analgesics. In this work, we asked if deletion of SGIP1 affects chronic nociception and analgesic effect of Delta 9-tetrahydrocannabinol (THC) and WIN 55,212-2 (WIN) in mice.Methods: We measured tactile responses of hind paws to increasing pressure in wild-type and SGIP1 knock-out mice. Inflammation in the paw was induced by local injection of carrageenan. To determine the mechanical sensitivity, the paw withdrawal threshold (PWT) was measured using an electronic von Frey instrument with the progression of the applied force.Results: The responses to mechanical stimuli varied depending on the sex, genotype, and treatment. SGIP1 knock-out male mice exhibited lower PWT than wild-type males. On the contrary, the female mice exhibited comparable PWT. Following THC or WIN treatment in male mice, SGIP1 knock-out males exhibited PWT lower than wild-type males. THC treatment in SGIP1 knock-out females resulted in PWT higher than after THC treatment of wild-type females. However, SGIP1 knock-out and wild-type female mice exhibited similar PWT after WIN treatment.Conclusions: We provide evidence that SGIP1, possibly by interacting with CB1R, is involved in processing the responses to chronic pain. The absence of SGIP1 results in enhanced sensitivity to mechanical stimuli in males, but not females. The antinociceptive effect of THC is superior to that of WIN in SGIP1 knock-out mice in the carrageenan-induced model of chronic pain.

Czech name

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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

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OECD FORD branch

30104 - Pharmacology and pharmacy

Project

<a href="/en/project/VK01010212" target="_blank" >VK01010212: New psychoactive substances: forensic-toxicology research center</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2024

Confidentiality

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

Name of the periodical

Cannabis and Cannabinoid Research

ISSN

2578-5125

e-ISSN

2378-8763

Volume of the periodical

Neuveden

Issue of the periodical within the volume

červenec 2024

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

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UT code for WoS article

001264754100001

EID of the result in the Scopus database

2-s2.0-85198636588