Role of the endocannabinoid system in the emotional manifestations of osteoarthritis pain.

The levels of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol In this study, we investigated the role of the endocannabinoid system (ECS) in the emotional and cognitive alterations associated with osteoarthritis pain. The monosodium iodoacetate model was used to evaluate the affective and cognitive manifestations of osteoarthritis pain in type 1 (CB1R) and type 2 (CB2R) cannabinoid receptor knockout and wild-type mice, and the ability of CB1R (ACEA) and CB2R (JWH133) selective agonists to improve these manifestations during a three week time period.(2-AG) were measured in plasma and brain areas involved in the control of these manifestations. Knee osteoarthritis patients and healthy controls were recruited to evaluate pain, affective and cognitive symptoms, as well as plasma endocannabinoid levels and cannabinoid receptor gene expression in peripheral blood lymphocytes. The affective manifestations of osteoarthritis were enhanced in CB1R knockout mice and absent in CB2R knockouts. Interestingly, both ACEA and JWH133 ameliorated the nociceptive and affective alterations, whereas ACEA also improved the associated memory impairment. An increase of 2-AG levels in prefrontal cortex and plasma was observed in this mouse model of osteoarthritis. In agreement, an increase of 2-AG plasmatic levels and an up-regulation of CB1R and CB2R gene expression in peripheral blood lymphocytes were observed in osteoarthritis patients compared to healthy subjects. Changes found in these biomarkers of the ECS correlated with pain, affective and cognitive symptoms in these patients. The ECS plays a crucial role in osteoarthritis and represents an interesting pharmacological target and biomarker of this disease.