The highlights of the anandamide study are:
- LTP in the LEC-DG hippocampus pathway is reduced by osteoarthritis-related persistent pain.
- The rat hippocampus has lower dopamine and higher serotonin levels as a result of chronic pain.
- OA rats treated with the FAAH inhibitor URB597 had lower levels of pain and mechanical allodynia.
- The activation of cannabinoid receptors is CB1 receptor-dependent, as AM251 blocks that effect.
Abstract
Chronic pain is a complex, long-term illness that can lead to mood disorders, tension, and worry. Osteoarthritis (OA) is one of the primary causes of chronic suffering in adults and elderly individuals. The hippocampus’s neural circuitry, including monoamine dopamine and serotonin levels, has been shown to play a role in unpleasant emotions such as dread and avoidance behavior during the discomfort.
According to current pharmacological approaches, endocannabinoid system modulation may be an option for the treatment of OA-related pain. To investigate whether the activation of the endocannabinoid system affects pain perception and emotional behavior after 28 days in a rat model of osteoarthritis induced by intra-articular sodium monoiodoacetate administration, we used a mouse behavioral test (LTP) and brain biological markers in lateral entorhinal cortex-dentate gyrus pathways.
OA-related persistent pain results in working memory impairment and depressive-like behavior appearance decreases LTP, lowers dopamine levels, and increases serotonin levels in the rat dentate gyrus. URB597 treatment (i.p., 1 mg/kg) reduces hyperalgesia and mechanical allodynia while improving recognition memory and depressive live action, restoring LTP , and normalizing monoamine levels in the hippocampus. The impact was seen 60–120 minutes after administration and was blocked by AM251, indicating that URB597 works via the CB1 receptor to alleviate OA-related chronic discomfort at a behavioral level.
This article is part of the Special Issue on ‘Advances in pain mechanisms and therapeutic targets’”.
The detailed Material and methods, and results of anandamide oil study can be downloaded from the original article.
References:
Kędziora, M., Boccella, S., Marabese, I., Mlost, J., Infantino, R., Maione, S., & Starowicz, K. (2023). Inhibition of anandamide breakdown reduces pain and restores LTP and monoamine levels in the rat hippocampus via the CB1 receptor following osteoarthritis. Neuropharmacology, 222, 109304. https://doi.org/10.1016/j.neuropharm.2022.109304