Peripheral inflammation affects modulation of nociceptive synaptic transmission in the spinal cord induced by N‐arachidonoylphosphatidylethanolamine

0489989 - FGÚ 2019 RIV GB eng J - Článek v odborném periodiku
Nerandžič, Vladimír - Mrózková, Petra - Adámek, Pavel - Špicarová, Diana - Nagy, I. - Paleček, Jiří
Peripheral inflammation affects modulation of nociceptive synaptic transmission in the spinal cord induced by N‐arachidonoylphosphatidylethanolamine.
British Journal of Pharmacology. Roč. 175, č. 12 (2018), s. 2322-2356. ISSN 0007-1188. E-ISSN 1476-5381
Grant CEP: GA ČR(CZ) GA15-11138S; GA MŠMT(CZ) LH15279; GA MŠMT(CZ) ED1.1.00/02.0109
Institucionální podpora: RVO:67985823
Klíčová slova: Anandamide * TRPV1 * pain * cannabinoids
Obor OECD: Neurosciences (including psychophysiology
Impakt faktor: 6.583, rok: 2018

Endocannabinoids play an important role in modulating spinal nociceptive signalling, crucial for the development of pain. The cannabinoid CB1 receptor and the TRPV1 cation channel are both activated by the endocannabinoid anandamide, a product of biosynthesis from the endogenous lipid precursor N‐arachidonoylphosphatidylethanolamine (20:4‐NAPE). Here, we report CB1 receptor‐ and TRPV1‐mediated effects of 20:4‐NAPE on spinal synaptic transmission in control and inflammatory conditions. Spontaneous (sEPSCs) and dorsal root stimulation‐evoked (eEPSCs) excitatory postsynaptic currents from superficial dorsal horn neurons in rat spinal cord slices were assessed. Peripheral inflammation was induced by carrageenan. Anandamide concentration was assessed by mass spectrometry. While 20:4‐NAPE treatment inhibited the excitatory synaptic transmission in both naive and inflammatory conditions, peripheral inflammation altered the underlying mechanisms. Our data indicate that 20:4‐NAPE application induced mainly CB1 receptor‐mediated inhibitory effects in naive animals while TRPV1‐mediated mechanisms were also involved after inflammation. Increasing anandamide levels for analgesic purposes by applying substrate for its local synthesis may be more effective than systemic anandamide application or inhibition of its degradation.
Trvalý link: http://hdl.handle.net/11104/0284282