Effect of minocycline on development of diabetic neuropathic pain in rats

Abstract

Objective To investigate the effect of minocycline on development of diabetic neuropathic pain in rats and its mechanism. Methods Forty male Sprague-Dawley rats aged 6-8 weeks, weighting 180-220 g, were randomly assigned into 4 groups, with 10 rats in each group: normal control group (group C), normal+minocycline group (group C+M), diabetes mellitus group (group DM), diabetes+minocycline group (group DM+M). Diabetes models of rats in group DM and group DM+M were established by single intraperitoneal injection of streptozotocin (STZ, 65 mg/kg), and equal volume of normal saline was injected instead of STZ into group C and group C+M; the fasting blood glucose level was tested every week, and the rats of blood glucose level ≥16.6 mmol/L were selected otherwise by additional injection of STZ. Two weeks after that, the intervention treatment of rats was given by single intraperitoneal injection of minocycline (40 mg/kg) in group DM+M and group C+M. The thermal tail flick latency (TFL), thermal withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) were detected one day prior to the injection of STZ (T0), and one (T1), 2 (T2), 4 (T3) and 8 (T4) weeks after the injection of STZ. Eight weeks after that, the expressions of malondialdehyde (MDA) and superoxide dismutase (SOD) in the spinal dorsal of the rats were detected by principles of physical chemistry with enzyme standard instrument, and apoptotic cells in dorsal horn was detected by immunohistochemistry. Results As compared with those in group C and group C+M, TFL, TWL and MWT in group DM and group DM+M were significantly decreased at T2, T3 and T4 (P<0.05); TFL, TWL and MWT in group DM+M were significantly increased as compared with those in group DM, reaching their peak levels at T4, with significant differences (P<0.05). SOD level in group D and group DM was significantly lower than that in group C (P<0.05), and MDA level in group D and group DM was significantly higher than that in group C (P<0.05); as compared with group DM, group DM+M had higher SOD level and lower MDA level, with significant differences (P<0.05). The number of apoptotic cells in spinal dorsal of the rats in group DM was significantly larger than that in group C (P<0.05). Conclusion Minocycline can relieve diabetic neuropathy pain, and the underlying of mechanisms may be through anti-inflammatory, anti-oxidant stress, anti-apoptosis, and reducing the microglia activation in the spinal cord. Key words: Minocycline; Diabetic neuropathy pain; Inflammatory response; Cell apoptosis; Microglia activation