Neurotrophic factor derived from spinal cord glial cell line in rats with neuropathic pain involved in the modulation of dopamine D2 receptor agonists hyperalgesia

Abstract

Objective To study the effects of intrathecal injection of dopamine D2 receptor agonist quinpirole on expression of glial cell line-derived neurotrophic factor in the spinal cord in rats with chronic constrictive injury (CCI) and explore its possible mechanism of mediating antinociception.Methods In this study,models were established CCI in male Sprague-Dawley rats.The experiment was performed as 2 parts.In part one,30 CCI rats were randomly divided into 5 groups (n=6):CCI+saline (group NS),CCI+quinpirole 0.1 μg (group Q0.1),CCI+quinpirole 1 μg (group Q1),CCI+quinpirole 5 μg (group Q5),CCI+quinpirole 10μg (group Q 10).The drugs were injected intrathecally on day 7 after CCI,respectively.Paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured before and at 0.5,1,2,4,8 h and 16 h after intrathecal injection.In part two 54 CCI rats were randomly divided into 3 groups (group Q5,Q10 and NS,n=18).Group Q5 and Q10 were sacrificed at 0.5,1,2,4,8,16 h after intrathecal quinpirole 5,10 μg on day 7 after CCI.Group NS,a single intrathecal injection of saline 10 μl.Group M,another 6 normal rats as model control group.Another 6 normal rats as control group C.The expression of glial cell linederived neurotrophic fact (GDNF) in the spinal cord was determined by Western blot.Results Part one:compared with group NS,the PWMT and PWTL of group Q0.1 at each time point after injection had no statistically significant difference (P＞0.05).The PWMT and PWTL of 2 h of group Q1 [(4.3±1.5) g,(13.2±1.6) s].1,2,4 h of group Q5 [(4.7±1.6),(5.3±1.6),(4.7±2.1) g,(14.0±1.7),(15.2±1.5),(13.4±1.6) s] and Q10 [(6.0±1.3),(7.3±1.0),(5.3±2.1) g,(15.3±1.8),(17.5±1.2),(14.9±1.7) s] after drug administration were significantly promoted (P＜0.05).Part two:compared with group C,the expression of GDNF was significantly increased in group M (0.95±0.09)(P＜0.05).Compared with group M and NS,group Q5 [(1.47±0.12),(1.24±0.05)] and Q10[(1.63±0.08),(1.27±0.06)] significantly increased the expression of GDNF (P＜0.05),and it can last until 4 h after injection at least.Conclusions Intrathecal injection of quinpirole can significantly increase the level of GDNF expression in the spinal cord.At the same time,the pain behavior was improved.The upregulation of GNDF expression is involved in the modulation of dopamine D2 receptor agonist on neuropathic pain. Key words: Neuropathic pain; Dopamine agonist; Spinal; Glial cell line-derived neurotrophic fact; Intrathecal injection