R-Flurbiprofen Reduces Neuropathic Pain in Rodents by Restoring Endogenous Cannabinoids
Figure 4
Modulation of endocannabinoid levels by R-flrubiprofen in microglial cells (EOC20) and tissue.
a Endocannabinoids in EOC20 at baseline and after stimulation with LPS (1 mg/ml) with or without treatment with R-flurbiprofen (10 µM); n = 6 experiments per group. b Endocannabinoids in ipsi lateral L4/5 DRGs, c ipsi lateral dorsal horn of the spinal cord d and contra lateral forebrain cortex in the SNI model 7 days after nerve injury and treatment with 4.5 mg/kg R-flurbiprofen or vehicle twice daily in mice (n = 8 per group; P<0.05). AEA, anandamide; OEA, oleylethanolamine; PEA, palmitoylethanolamine; 1AG and 2AG, 1- and 2-arachidonoylglycerol were analyzed by LC-MS/MS. P<0.05 for all tests. e PPARγ activity in nuclear protein extracts of L4/5 DRGs, spinal cord and forebrain cortex in naïve mice and in nerve injured mice 7 days after SNI. Mice were treated with vehicle or 4.5 mg/kg R-flurbiprofen twice daily. Results represent pooled extracts of 6 mice in each group. f Core body temperature in mice (mean ± s.e.m. shadowed area) treated with the CB1 agonist, WIN55,212-2, the FAAH inhibitor URB597, R-flurbiprofen and respective vehicles (n = 6 per group). Vehicles 10% or 50% DMSO did not produce changes of the core temperature as compared to phosphate buffered saline and were summarized. The decrease of core temperature in vehicle treated mice is caused by resting during the day. Hypothermia in mice is defined as core temperature <35°C.