Role of spinal dopamine D2 receptors in analgesic effect of duloxetine in rats with neuropathic pain

Abstract

Objective To evaluate the involvement of spinal dopamine D2 receptors in the analgesic effect of duloxetine in neuropathic pain rat models. Methods Experiment I, twenty-four male SD rats, weighting 200-250 g, were randomly divided into 4 groups (n=6), respectively receiving intraperitoneal injection of dimethyl sulfoxide (DMSO) (group DS), 3 mg/kg duloxetine (group D1), 10 mg/kg duloxetine (group D2), and 30 mg/kg duloxetine (group D3). These treatments started 7 days after spinal L5 nerve ligation, and the mechanical withdraw threshold (MWT) was determined at 7 time points: before spinal nerve ligation (SNL) surgery (T0), before duloxetine injection (T1), and 15 min (T2), 30 min (T3), 60 min (T4), 120 min (T5), 180 min (T6) after duloxetine injection. Experiment Ⅱ, twenty-four male SD rats, weighting 200-250 g, were subjected to intrathecal catheters insertion, and were randomly divided into 4 groups (n=6). In group DS, DMSO (group DS+DS) or 30 μg sulpride (group Sul+DS) was administered intrathecally 15 min before DMSO intraperitoneal injection. In group Dul, DMSO (group DS+Dul) or 30 μg sulpride (group Sul+Dul) was administered intrathecally 15 min before 30 mg/kg duloxetine intraperitoneal injection. Mechanical paw withdraw threshold was determined before and after duloxetine or DMSO injection. Experiment Ⅲ, twelve male SD rats, weighting 200-250 g, were randomly divided into 2 groups (n=6), respectively receiving intraperitoneal injection of DMSO (group N) and 10 mg/kg duloxetine (group D). Then, the concentrations of dopamine in the spinal cord were measured with microdialysis before and after injection of duloxetine or DMSO injection. Results Compared with group DS, the MWT was significantly increased in group D3 at T2-T6 (P<0.05). Compared with group DS+Dul, the MWT was dramatically decreased in group Sul+Dul at T2-T6 (P<0.05). Compared with group N, the concentrations of dopamine in the spinal cord was dramatically increased in group D at T8-T13 (P<0.05). Conclusions Duloxetine relieved spinal nerve injury-induced neuropathic pain in rats, which may be related to the enhancement of dopamine release and activation of D2 receptors in the spinal cord dorsal horn. Key words: Neuropathic pain; Duloxetine; Spinal cord dorsal horn; Dopamine D2 receptors