Role of calcium/calmodulin-dependent protein kinase II in cognitive dysfunction caused by chronic pain in rats

Abstract

Objective To evaluate the role of calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) in cognitive dysfunction caused by chronic pain in rats.Methods The experiment was performed in 2 parts.In experiment Ⅰ,24 pathogen-free male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 4 groups (n =6 each) using a random number table:sham operation group (group S),m-AIP injected before sham operation group (group M-S),chronic sciatic nerve injury group (group N-C),and m-AIP injected before chronic constriction injury (CCI) group (group M-C).The sciatic nerve was only exposed but not ligated.Chronic pain was induced by CCI in N-C and M-C groups.The animals were anesthetized with intraperitoneal 1％ pentobarbital sodium.The sciatic nerve was exposed and 4 ligatures were placed on the sciatic nerve at 1 mm intervals.Normal saline 20 μ1 and m-AIP 20 μ/ were injected intrathecally at 15 min before sham operation in S and M-S groups,respectively,and at 15 min before CCI in N-C and M-C groups,respectively.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before CCI and on 4,7,10,14,17,21 and 28 days after CCI.Step-through latency (STL) was measured before CCI and on 7,14,21 and 28 days after CCI.In experiment Ⅱ,18 pathogen-free male Sprague-Dawley rats,weighing 180-220 g,were randomly divided into 3 groups (n =6 each) using a random number table:m-AIP injected after sham operation group (group C-N),control after CCI group (group C-N) and m-AIP injected after CCI group (group C-M).Group S-M received intrathecal injection of m-AIP 20 μl at 7 days after sham operation.Normal saline 20 μl and m-AIP 20 μ/ were injected intrathecally at 7 days after CCI in C-N and C-M groups,respectively.MWT,TWL and STL were measured before administration and at 2,4 and 8 h after administration.Results In experiment Ⅰ,compared with group S,MWT was significantly decreased at each time point after CCI,TWL was shortened at each time point after CCI and STL was shortened on 7,14 and 21 days after CCI in N-C group,and MWT was significandy decreased at each time point,TWL was shortened at each time point,and STL was shortened on 14 and 21 days after CCI in group M-C.Compared with group N-C,MWT was significantly increased on 4,7 and 10 days after CCI,TWL was prolonged on 4 and 7 days after CCI,and STL was prolonged on 7 days after CCI in group M-C.In experiment Ⅱ,compared with group S-M,MWT was significantly decreased,and TWL and STL were shortened at each time point after administration in C-N group,and TWL at 8 h after administration and STL at each time point after administration were shortened,MWT was decreased at 8 h after administration,and no significant change was found in MWT and TWL at 2 and 4 h after administration in group C-M Compared with group C-N,MWT was significantly increased,and TWL was prolonged at 2 and 4 h after administration,and no significant change was found in STL at each time point after administration in group C-M.Conclusion CaMK Ⅱ is involved in the development of cognitive dysfunction caused by chronic pain in rats. Key words: Calcium-calmodulin-dependent protein kinase type 2; Neuralgia; Cognition disorders