Protective Effects of Paroxetine on Neuropathic Pain in Diabetic Rats and the Possible Mechanism

OBJECTIVE To observe the protective effects of paroxetine (PAT) on neuropathic pain in diabetic rats and to research the possible mechanism. METHODS Twenty-four male SD rats were randomly divided into three groups (n=8):control group, diabetes mellitus (DM) group and DM+PAT group. Diabetes mellitus was induced via single intraperitoneal injection of streptozotocin (STZ) at a dose of 75 mg·kg^-1. Paw withdrawal mechanical threshold (PWMT) was measured before modeling and on 7, 14 and 28 d after STZ injection. On day 28 after STZ injection, all rats were sacrificed, lumbar segments (L₄-L₆) of spinal cord were recovered for pathologic observation. Paraffin slides of the spinal cord were prepared with Nissl's staining for detecting the pathologic changes. Apoptosis in dorsal horn spinal cord neurons was detected by TUNEL staining. Western blot was used to detect the expression levels of HO-1 in spinal cord. RESULTS Pain threshold to mechanical stimuli in DM group and DM+PAT group was significantly decreased compared with control group (P<0.05), while rats in DM+PAT group had higher threshold to mechanical stimuli on day 28 after STZ injection than rats in DM group (P<0.05). Microscopic examination showed that dorsal horn of the spinal cord in DM group was atrophic; the number of neurons was significantly decreased and the Nissl's bodies in spinal cord were diminished, while these changes in DM+PAT group were significantly weakened. The expression levels of HO-1 in spinal cord in DM+PAT group were significantly increased compared with DM group. CONCLUSION Paroxetine can attenuate neuropathic pain in diabetic rats and protect the neurons in spinal cord, the possible mechanism may be explained by increasing the expression of HO-1 in spinal dorsal horn.