Pharmacological Study Design

In this study, behavioral studies were performed under intraperitoneal (i.p.) administrations to be consistent (and can be correlated) with our earlier published results (Gao et al., 2013, 2019a). The timeline of pharmacological interventions was illustrated in the Supplementary Figure 1. SN/Vehicle was given 60 min prior to the application of LGZ/PCM/Vehicle. Pain behavioral measurement (measurement of mechanical allodynia and heat hyperalgesia) was performed after application of LGZ/PCM/Vehicle, for 240 min. This pharmacological intervention strategy was inherited from our previous study (Gao et al., 2019a), in which we show that the analgesic efficacy of SN combination is optimal when SN was given 60 min prior to the combinational drug. To assess the analgesic effects of SN combinations in incisional pain and inflammatory pain models, animals were randomly assigned to following treatment groups (6–8 rats/mice per group): SN low dose group (SN 10 mg/kg); SN middle dose group (SN 20 mg mg/kg); SN high dose group (SN 80 mg/kg); LGZ low dose group (LGZ 10 mg/kg); LGZ middle dose group (LGZ 20 mg/kg); LGZ high dose group (LGZ 80 mg/kg); SN+LGZ low dose group (SN 10 mg/kg + LGZ 10 mg/kg); SN+LGZ middle dose group (SN 20 mg/kg + LGZ 10 mg/kg); SN+LGZ high dose group (SN 20 mg/kg + LGZ 20 mg/kg); PCM low dose group (PCM 10 mg/kg); PCM middle dose group (PCM30 mg/kg); PCM high dose group (PCM 100 mg/kg); SN+PCM low dose group (SN 10 mg/kg + PCM 10 mg/kg); SN+PCM middle dose group (SN 20 mg/kg + PCM 10 mg/kg); SN+PCM high dose group (SN 20 mg/kg + PCM 30 mg/kg); and Vehicle groups (for all separate experiments).