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

  • Mohammad AlsalemEmail author
  • Mansour Haddad
  • Sara A. Aldossary
  • Heba Kalbouneh
  • Ahmad Altarifi
  • Sahar M. Jaffal
  • Manal A. Abbas
  • Nour Aldaoud
  • Khalid El-Salem
Original Article


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.


Peroxisome proliferator-activated receptor α Cannabinoid receptor 1 Osteoarthritis Pain 



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

Compliance with ethical standards

Conflict of interest

Authors declare no conflict of interest.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Faculty of MedicineThe University of JordanAmmanJordan
  2. 2.Faculty of PharmacyPhiladelphia UniversityAmmanJordan
  3. 3.Faculty of Clinical PharmacyKing Faisal UniversityHofufSaudi Arabia
  4. 4.Faculty of MedicineJordan University of Science and TechnologyIrbidJordan
  5. 5.Faculty of ScienceThe University of JordanAmmanJordan
  6. 6.Faculty of Pharmacy and Medical SciencesAl-Ahliyya Amman UniversityAmmanJordan

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