(R)-Duloxetine hydrochloride

Sprague-Dawley (male; weight 250-300 g; skin incision plus extension model on dorsothoracic skin)^[1]

2 mg (ipsilateral s.c.); 10 mg (i.p.); 10 mg (contralateral s.c.)

s.c. (ipsilateral to incision; single injection; 1 hour prior to surgery); i.p. (single injection; 1 hour prior to surgery); s.c. (contralateral to incision; single injection; 1 hour prior to surgery)

Reduced 4 g von Frey allodynia 5-day AUC to 11% of control at 0.5 cm, 27% of control at 1.0 cm, 41% of control at 2.0 cm, and 46% of control at the contralateral site following 2 mg ipsilateral subcutaneous administration.
Reduced 15 g von Frey hyperalgesia 5-day AUC to 1% of control at 0.5 cm, 11% of control at 1.0 cm, and 65% of control at the contralateral site following 2 mg ipsilateral subcutaneous administration.
Produced analgesic effects on allodynia from time 0 through 5 days at all ipsilateral sites, with contralateral allodynia relief lasting 1 day post-injection after 2 mg ipsilateral subcutaneous administration.
Produced antihyperalgesic effects persisting for 5 days at ipsilateral sites, with responses below baseline at 0.5-1 cm from day 0 to day 3 after 2 mg ipsilateral subcutaneous administration.
Reduced 4 g allodynia 5-day AUC to 31% of control at 0.5 cm, 37% of control at 1.0 cm, 54% of control at 2.0 cm, and 72% of control at the contralateral site following 10 mg intraperitoneal administration.
Reduced 15 g hyperalgesia 5-day AUC to 35% of control at 0.5 cm, 40% of control at 1.0 cm, 48% of control at 2.0 cm, and 52% of control at the contralateral site following 10 mg intraperitoneal administration.
Produced immediate systemic allodynia reduction post-injection following 10 mg intraperitoneal administration.
Produced minimal analgesic effects on allodynia and hyperalgesia at the ipsilateral incision side, with 4 g allodynia AUC values at 89%-105% of control and 15 g hyperalgesia AUC values at 84%-92% of control across 0.5-2.0 cm ipsilateral sites following 10 mg contralateral subcutaneous administration.