The multiplicity of spinal AA-5-HT anti-nociceptive action in a rat model of neuropathic pain
PBN-AR
Instytucja
Instytut Farmakologii im. Jerzego Maja Polskiej Akademii Nauk
Źródłowe zdarzenia ewaluacyjne
Informacje podstawowe
Główny język publikacji
en
Czasopismo
PHARMACOLOGICAL RESEARCH
ISSN
1043-6618
EISSN
Wydawca
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI
URL
Rok publikacji
2016
Numer zeszytu
Strony od-do
251-263
Numer tomu
111
Identyfikator DOI
Liczba arkuszy
Słowa kluczowe
en
Cannabinoid receptors
TRPV1
FAAH
Endocannabinoids
N-acylethanolamines
Neuropathic pain
Streszczenia
Język
en
Treść
There is considerable evidence to support the role of anandamide (AEA), an endogenous ligand of cannabinoid receptors, in neuropathic pain modulation. AEA also produces effects mediated by other biological targets, of which the transient receptor potential vanilloid type 1 (TRPVI) has been the most investigated. Both, inhibition of AEA breakdown by fatty acid amide hydrolase (FAAH) and blockage of TRPVI have been shown to produce anti-nociceptive effects. Recent research suggests the usefulness of dual-action compounds, which may afford greater anti-allodynic efficacy. Therefore, in the present study, we examined the effect of N-arachidonoyl-serotonin (AA-5-HT), a blocker of FAAH and TRPV1, in a rat model of neuropathic pain after intrathecal administration. We found that treatment with AA-5-HT increased the pain threshold to mechanical and thermal stimuli, with highest effect at the dose of 500 nM, which was most strongly attenuated by AM-630, CB2 antagonist, administration. The single action blockers PF-3845 (1000 nM, for FAAH) and I-RTX (1 nM, for TRPV1) showed lower efficacy than AA-5-HT. Moreover AA-5-HT (500 nM) elevated AEA and palmitoylethanolamide (PEA) levels. Among the possible targets of these mediators, only the mRNA levels of CB2, GPR18 and GPR55, which are believed to be novel cannabinoid receptors, were upregulated in the spinal cord and/or DRG of CCI rats. It was previously reported that AA-5-HT acts in CB1 and TRPV1-dependent manner after systemic administration, but here for the first time we show that AA-5-HT action at the spinal level involves CB2, with potential contributions from GRP18 and/or GPR55 receptors. (C) 2016 Elsevier Ltd. All rights reserved.
Cechy publikacji
Original article
Original article presents the results of original research or experiment.
Oryginalny artykuł naukowy
Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Inne
System-identifier
PBN-R:783198
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