Analgesic Effect Of Slow Released Betamethasone Dipropionate Microparticles In Rat Neuropathic Pain

Objective:To investigate the analgesic effect of betamethasone dipropionate-poly ethylene glycol-poly lactic acid (BDP-PELA) microparticles and extracellular signal-regulated kinase (ERK) expression in rat spinal cord of sciatic nerve chronic constriction injury (CCI) induced neuropathic pain.Methods:We prepared three BDP-PELA microparticles with ratios of poly ethylene glycol (PEG) to poly lactic acid (PLA) are 2 kDa:20 kDa (20k),2 kDa:30 kDa (30k) and 2 kDa:70 kDa (70k) as the polymeric materials, besides PELA copolymer with PLA 70kDa and PEG 2kDa were prepared and expressed as PP. Ninety six rats were randomly divided into six groups (n=16):sham operation group (SH group); CCI group; BDP group; 20k group; 30k group; 70k group. Mechanical withdraw threshold (MWT) and thermal withdrawal latency (TWL) of the rats were measured on pre-operative day 1, post-operative day 3,5,7,10,13 and 15. Activation of spinal ERK was assessed on post-operative day 3 and 10 by immunohistochemistry. Another twenty five rats were randomly divided into five groups (n=5):SH group; PP group; 20k group; 30k group; 70k group. The groups used for histological evaluation received no sciatic nerve ligation. The morphology of the optical myelin was observed by luxol fast blue (LFB) myelin stain on day 28.Results:Compared with CCI group, the analgesic effect of BDP group continued over a period of 5 days (P<0.05); 20k group,30k group,70k group lasted for 7,10,13 days, respectively (P<0.05). Compared with CCI group, the expression of spinal pERK were suppressed in BDP,20k,30k and 70k group on 3 days after surgery (P<0.05); pERK expression in 70k group were lower than that in CCI group and BDP group on 10 days after surgery (P<0.05). The difference in the density of the LFB stain between SH group and the microparticle groups was not statistically significant (P>0.05).Conclusion:Single sciatic nerve injection with BDP-PELA microparticles provides long-term analgesic effect, this effect is related to the suppression of spinal ERK activation, PEL A microspheres could be used safely to the sites surrounding the sciatic nerve..