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Role of cannabinoid receptor 1 and the peroxisome proliferator-activated receptor α in mediating anti-nociceptive effects of synthetic cannabinoids and a cannabinoid-like compound

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Abstract

Osteoarthritis (OA) is characterized by cartilage degeneration, subchondral sclerosis, and pain. Cannabinoids have well-established anti-nociceptive properties in animal models of chronic pain. The aim of this study is to evaluate the anti-nociceptive effects of synthetic cannabinoids (WIN-55,212 and HU210) and the cannabinoid-like compound palmitoylethanolamide (PEA) in rat models of OA and to assess the role of cannabinoid receptor 1 (CB1) and the peroxisome proliferator-activated receptor α (PPARα) in mediating these effects. Intra-articular injection of monosodium iodoacetate (MIA) in the knee joint was used as a model of osteoarthritis. The von Frey filament test and weight-bearing difference were used to assess the anti-nociceptive effects of WIN-55,212, HU210, and PEA on MIA-induced OA in rats. Open-field locomotor activity system was used confirm the analgesic effects of those compounds. HU210, WIN55, 212, and PEA in a dose-dependent manner restored the paw withdrawal threshold (PWT) and the weight-bearing difference induced by MIA injection. SR141716A (a CB1 antagonist) significantly reversed the anti-nociceptive effects of all the administered drugs in terms of PWT. However, in terms of weight-bearing difference, SR141716A significantly reduced the anti-nociceptive effect of HU210 but not PEA or WIN55, 212. GW6471 (a PPARα antagonist) significantly reversed the anti-nociceptive effects of PEA but not those of HU210 or WIN55, 212. HU210, WIN55, 212 and PEA significantly restored the MIA-induced reduction in locomotor activity. In conclusions, both CB1 and PPARα receptors are involved in mediating pain in osteoarthritis. Therefore, targeting these receptors may be of great clinical value.

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Acknowledgements

This work was sponsored by the deanship of academic research in The University of Jordan.

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Authors and Affiliations

  1. Faculty of Medicine, The University of Jordan, Amman, 11942, Jordan

    Mohammad Alsalem, Heba Kalbouneh & Nour Aldaoud

  2. Faculty of Pharmacy, Philadelphia University, Amman, Jordan

    Mansour Haddad

  3. Faculty of Clinical Pharmacy, King Faisal University, Hofuf, Saudi Arabia

    Sara A. Aldossary

  4. Faculty of Medicine, Jordan University of Science and Technology, Irbid, 22110, Jordan

    Ahmad Altarifi & Khalid El-Salem

  5. Faculty of Science, The University of Jordan, Amman, 11942, Jordan

    Sahar M. Jaffal

  6. Faculty of Pharmacy and Medical Sciences, Al-Ahliyya Amman University, Amman, 19328, Jordan

    Manal A. Abbas

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Alsalem, M., Haddad, M., Aldossary, S.A. et al. Role of cannabinoid receptor 1 and the peroxisome proliferator-activated receptor α in mediating anti-nociceptive effects of synthetic cannabinoids and a cannabinoid-like compound. Inflammopharmacol 27, 1131–1142 (2019). https://doi.org/10.1007/s10787-019-00584-7

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