Clonidine and dexmedetomidine's effect on the altered expressions of growth associated protein-43 mRNA in rat dorsal root ganglion during the development of chronic neuropathic pain

Abstract

To explore the effects of α(2) adrenergic receptor (α(2)AR) agonists clonidine and dexmedetomidine on the injury model of peripheral nerve chronic constriction in rats. A total of 72 male SD rats weighing 180 - 250 g were randomly divided into 4 groups (n = 18 each). In sham operation group (S), the right sciatic nerves were exposed but not ligated. But, in other groups, four ligatures were placed around the right sciatic nerve according to the Bennett's method. From the instant after operation, 0.4 mg × kg(-1)× d(-1) clonidine and 50.0 µg × kg(-1)× d(-1) were injected intraperitoneally into the clonidine group (CL) and dexmedetomidine group (Dex) daily. And the same volume of normal saline was injected into the S and CCI groups (C) respectively. Mechanical and thermal pain thresholds were measured by paw withdrawal latencies at Day 1 pre-operation and Day 3, 7 and 14 post-operation. After that, the L(4-6) dorsal root ganglions to chronic constriction injured sciatic nerves were harvested. Reverse transcription-polymerase chain reaction (RT-PCR) and agarose gel electrophoresis were used to examine the expression of GAP-43 mRNA. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) of groups C, CL and Dex markedly decreased and the expression of GAP-43 mRNA in dorsal root ganglions significantly increased at Days 3, 7 and 14 post-operation versus those at pre-operation and group S (P < 0.05). TWL and MWT of groups CL and Dex at Days 7 and 14 post-operation significantly increased while the expression of GAP-43 mRNA in dorsal root ganglions markedly decreased versus those of group C (P < 0.05). TWL and MWT of group Dex were significantly higher while the expression of GAP-43 mRNA in dorsal root ganglions was lower than those of group CL (P < 0.05). Compared with Day 3, TWL and MWT of groups C, CL and Dex markedly decreased while the expression of GAP-43 mRNA significantly increased in dorsal root ganglions at Day 7 (P < 0.05). Compared with Day 7, TWL and MWT of groups CL and Dex markedly increased while the expression of GAP-43 mRNA in dorsal root ganglions significantly decreased at Day 14 (P < 0.05). Clonidine and dexmedetomidine both show evident analgesic effects on chronic neuropathic pain in rats probably through a reduction of nerve regeneration. But dexmedetomidine has a better efficacy due to of its high selectivity of α(2)AR.