Fig. 1.

(A) Chemical structure of GW405833, also referred to as L768242 (Gallant et al., 1996; Valenzano et al., 2005). Cayman Chemical (cat. no. 20219) and Tocris Bioscience (cat. no. 2374) identify this ligand as a selective, high-affinity CB₂ receptor partial agonist. (B and C) Timeline for the dose response of GW405833 and blockade with antagonist in PSNL and CFA model. (B) In the PSNL model, the baseline was tested a day before the surgery. Animals were allowed (≥14 days) to fully develop neuropathic pain before pharmacologic manipulations. After the full establishment of neuropathic pain, different doses of GW405833 were tested in ascending order with variable intervals to ensure no carryover effect. Specifically, 0 mg/kg was tested, followed by 3 mg/kg on the same day with 3- to 4-hour intervals; 10 mg/kg was then tested the next day, followed by 30 mg/kg tested 2 days later. The CB₁ or CB₂ antagonist was tested 3 or 4 days after the last dose of 30 mg/kg. Groups: C57BL/6J, n = 6 (males); CB₂KO, n = 6 (males); CD1, n = 8 (mixed sex); CB₁KO, n = 8 (mixed sex). (C) In the CFA model, the baseline was tested on the same day before the CFA injection; the test of dose response started 48 hours after the injection. The timeline for the dose response of GW405833 was the same as the timeline in PSNL model. Groups: C57BL/6J, n = 8 (mixed sex); CB₂KO, n = 8 (mixed sex); CD1, n = 8 (males); CB₁KO: n = 6 (males).