Peripheral inflammation alters N-arachidonoylphosphatidylethanolamine (20:4-NAPE) induced modulation of nociceptive spinal cord synaptic transmiss

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Title: Peripheral inflammation alters N-arachidonoylphosphatidylethanolamine (20:4-NAPE) induced modulation of nociceptive spinal cord synaptic transmiss
Author(s): Nerandzic, V
Mrozkova, P
Adamek, P
Spicarova, D
Nagy, I
Palecek, J
Item Type: Journal Article
Abstract: Background and Purpose Endocannabinoids play an important role in modulati ng spinal nociceptive signalling, crucial for the development of pain. The cannabinoid recept or 1 (CB1) and the transient receptor potential cation channel subfamily V member 1 (TRPV 1) are both activated by the endocannabinoid anandamide that is a product of bio synthesis from the endogenous lipid precursor N1arachidonoylphosphatidylethanolamine (2 0:41NAPE). Here we are first to report CB1 receptor1 and TRPV11mediated effects of 20:41NA PE application on spinal synaptic transmission in control and inflammatory conditions . Experimental Approach Spontaneous (sEPSCs) and dorsal root stimulation1ev oked (eEPSCs) excitatory postsynaptic currents from superficial dorsal horn neurons in ra t spinal cord slices were assessed. Peripheral inflammation was induced by carrageenan. Anandamide concentration was assessed by mass spectrometry. Key Results Application of 20:41NAPE increased anandamide conce ntration in vitro . 20:41NAPE (20 μM) decreased sEPSCs frequency and eEPSCs amplitude in control and inflammatory conditions. The inhibitory effect of 20:41NAPE was sensitive to CB1 antagonist PF514273 (0.2 μM) in both conditions, but to the TRPV1 antagonist SB3667 91 (10 μM) only after inflammation. After inflammation 20:41NAPE increased sEPSCs frequ ency in the presence of PF514273 and this increase was blocked by SB366791. Conclusions and Implications While 20:41NAPE treatment produced an inhibitory ef fect on excitatory synaptic transmission in both naive and inflammatory conditions, peripher al inflammation altered the underlying mechanisms. Our data indicate that 20:41NAPE applic ation induced mainly CB1 receptor1 mediated inhibitory effects in naive animals while TRPV11mediated mechanisms were also involved after inflammation. Increasing anandamide levels for analgesic purposes by applying substrate for its local synthesis may be superior to systemic anandamide application or inhibition of its degradation.
Publication Date: 1-Jun-2018
Date of Acceptance: 27-Apr-2017
ISSN: 1476-5381
Publisher: Wiley
Start Page: 2322
End Page: 2336
Journal / Book Title: British Journal of Pharmacology
Volume: 175
Issue: 12
Sponsor/Funder: Wellcome Trust
British Journal of Anaesthesia
Commission of the European Communities
Funder's Grant Number: 081637/Z/06/Z
Copyright Statement: © 2017 The British Pharmacological Society
Keywords: 1115 Pharmacology And Pharmaceutical Sciences
Pharmacology & Pharmacy
Publication Status: Published
Online Publication Date: 2017-05-05
Appears in Collections:Division of Surgery
Faculty of Medicine

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