Inhibition of anandamide breakdown reduces pain and restores LTP and monoamine levels in the rat hippocampus via the CB1 receptor following osteoarthritis

• Published in: Neuropharmacology Vol. 222; p. 109304
• Main Authors: Kędziora, Marta, Boccella, Serena, Marabese, Ida, Mlost, Jakub, Infantino, Rosmara, Maione, Sabatino, Starowicz, Katarzyna
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01-01-2023
• Subjects: Anandamide; Chronic pain; Dopamine; Hippocampus; Long term potentiation; Osteoarthritis; Long term potentiation; Dopamine; Osteoarthritis; Chronic pain; Hippocampus; Anandamide
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2022.109304

Chronic pain is a persistent, complex condition that contributes to impaired mood, anxiety and emotional problems. Osteoarthritis (OA) is one of the major causes of chronic pain in adults and elderly people. A substantial body of evidence demonstrate that hippocampal neural circuits, especially monoamine dopamine and serotonin levels, contributes to negative affect and avoidance motivation experienced during pain. Current pharmacological strategies for OA patients are unsatisfying and the endocannabinoid system modulation might represent an alternative for the treatment of OA-related pain. In the present study, we used a rat model of osteoarthritis induced by intra-articular injection of sodium monoiodoacetate to assess, 28 days post-induction, the contribution of endocannabinoid system on the possible alteration in pain perception and affective behavior, in LTP and monoamine levels in the lateral entorhinal cortex-dentate gyrus pathway. The results show that OA-related chronic pain induces working memory impairment and depressive-like behavior appearance, diminishes LTP, decreases dopamine levels and increases serotonin levels in the rat dentate gyrus. URB597 administration (i.p., 1 mg/kg) reduces hyperalgesia and mechanical allodynia, improves recognition memory and depressive-live behavior, restores LTP and normalizes monoamine levels in the hippocampus. The effect was observed 60–120 min post-treatment and was blocked by AM251, which proves the action of URB597 via the CB1 receptor. Therefore, our study confirms the role of anandamide in OA-related chronic pain management at the behavioral and hippocampal levels.
This article is part of the Special Issue on ‘Advances in mechanisms and therapeutic targets relevant to pain’.
•Osteoarthritis-related chronic pain diminishes LTP in the LEC-DG hippocampus pathway.•Chronic pain decreases dopamine and increases serotonin levels in the rat hippocampus.•The FAAH inhibitor URB597 reduces pain and mechanical allodynia in OA rats.•URB597 restores LTP and normalizes monoamine levels 60–120 min posttreatment.•The effect of URB597 is CB1 receptor dependent since it is blocked by its antagonist AM251.