Abstract:

Objective To explore the effect of intrathecal injection of adeno⁃associated virus（AAV）⁃mediated brain⁃derived neurotrophin factor（BDNF）in spinal nerve ligation（SNL）rats on neuropathic pain andits possible mechanism. Methods Fifty⁃six SD rats were randomly divided into normal，SNL，normal saline（NS），BDNF⁃free AAV（AAV0），AAV⁃BDNF（BDNF），AAV⁃BDNF +potassium chloride cotransporter 2（KCC2）antagonist（BDNF + Furos）and AAV⁃BDNF + NS（BDNF+NS）groups. Mechanical withdrawal thresholds（MWTs）and thermal withdrawal latencys（TWLs）of the rats in each group were measured before modeling and 0，3，7，14，and 21 days after intrathecal injection. The expression of BDNF and KCC2 in the spinal dorsal horn was detectedby Western Blot after test. Results Compared with the normal group，the MWTs and TWLs of other groupsdecreased significantly after modeling（P < 0.001）. As compared with the SNL，NS and AAV0 groups，the MWTand TWL of the BDNF group increased at 14 and 21 days after injection（P < 0.001）. After intrathecal injection，the MWT and TWL of the BDNF+Furos group was significantly lower than those of the BDNF and BDNF+NSgroups（P < 0.001）. At 21 days after injection，the expression of BDNF and KCC2 in the BDNF group was signifi⁃cantly higher than those in SNL，NS and AAV0 groups（P < 0.001）. The expression of KCC2 in the BDNF+Furosgroup decreased compared to those in the BDNF and BDNF+NS groups（P < 0.001）. Conclusion The intrathecalexpression of BDNF mediated by AAV can play an analgesic role in SNL rats，which is related to the upregulationof KCC2.

Key words: brain?derived neurotrophic factor, adeno?associated virus, potassium chloride cotransport?er 2, spinal nerve ligation model, neuropathic pain