Figure 9.

(R)-7 reverses mechanical hypersensitivity in the tibial-nerve injury model of neuropathic pain. (A) Diagram of the sural, tibial, and common peroneal terminal nerve branches of the sciatic nerve and their dorsal root origins. Neuropathic painlike behavior was induced by ligation of the tibial nerve and 2–4 mm of the nerve distal to the ligation was removed. (B) Withdrawal threshold (in millinewtons, mN) in response to von Frey stimulation to the paw ipsilateral to the tibial-nerve injury following a single, intraperitoneal administration of the indicated drugs (10 mg/kg, n = 5–6) on day 14 after injury. A single injection of (R)-7 almost completely reversed tibial-nerve injury induced mechanical hypersensitivity (p < 0.05; Student’s t test) compared with predrug baseline. As a comparison, (R)-2 and (R)-1 also reversed mechanical hypersensitivity.¹¹ Compound (S)-3 and the antiseizure drug carbamazepine (CBZ) were without effect.