Effect of gabapentin on neurogenesis in hippocampal dentate gyrus of adult rats with co-disease of chronic pain and depression.

Abstract

Chronic pain lasts for more than 3 months and is often associated with negative emotions such as depression and anxiety. Long-term chronic pain stress can lead to plastic changes in hippocampal structure and function. In addition to its analgesic effect, gabapentin also has certain cerebral protective effects. This study aims to observe the effect of gabapentin on neurogenesis in hippocampal dentate gyrus (DG) of the adult rats with co-disease of chronic pain and depression. The adult rats were randomly divided into 4 groups: A sham operation (Sham) group, a comorbidity model+normal saline (CCI+Veh) group (1 mL saline), a comorbidity model+low-dose gabapentin (CCI+LG) group (diluting gabapentin with normal saline to 1 mL at the dose of 30 mg/kg), and a comorbidity model+high-dose gabapentin (CCI+HG) group (diluting gabapentin with normal saline to 1 mL at the dose of 100 mg/kg) (8 rats per group). The comorbidity model was established by sciatic nerve encirclement. On the 30th day after operation, normal saline, low-dose gabapentin, and high-dose gabapentin were given intraperitoneally, respetively, for 7 consecutive days. The paw withdrawal mechanical threshold (PWMT) of the right hindlimb was measured before the operation and on the 7th, 14th, 21th, 28th, and 40th day after the operation. The time of immobility and sugar water preference rate were measured by forced swimming test and sugar water preference test, respectively, on the 28th and 40th day after the operation. The number of doublecortin (DCX) positive neurons and the expression of brain-derived neurotrophic factor (BDNF) in hippocampal dentate gyrus were observed by immunohistochemical staining, and the morphological changes of the hippocampal neurons were observed by Golgi staining. Compared with the Sham group, the PWMT of the CCI comorbidity model rats reached the lowest level on the 7th day after the operation and lasted until the 28th day after the operation, and remained at a low level on the 40th day after the operation (all P<0.05). Compared with the CCI+Veh group, the PWMT in the CCI+LG group and the CCI+HG group was increased on the 40th day after the operation (all P<0.05). Compared with the Sham group, the time of immobility in the CCI comorbidity model rats was increased significantly (all P<0.01) and the sugar water preference rate was decreased significantly (all P<0.01) on the 28th day after the operation. Compared with the CCI+Veh group, the time of immobility in the CCI+HG group was shortened (P<0.05) and the sugar water preference rate was significantly increased (P<0.01) on the 40th day after the operation. Compared with the CCI+Veh group, the number of DCX positive cells in hippocampal DG of the CCI+LG group and the CCI+HG group was increased, and that in the CCI+HG group was increased more significantly (P<0.05). Compared with the Sham group, the expression of BDNF in hippocampal DG was decreased in the CCI+Veh group (P<0.05). Compared with the CCI+Veh group, the expression of BDNF in hippocampal DG and the length of dendritic spines of the hippocampal neurons were increased in the CCI+HG group (all P<0.05). Gabapentin can relieve chronic pain and depression-like behavior in rats with chronic pain and depression, and promote neurogenesis of hippocampal dentate gyrus neurons.