Effect of intrathecal morphine preconditioning on expression of nerve growth factor in dorsal root ganglia in a rat model of myocardial ischemia-reperfusion

Abstract

Objective To investigate the effect of intrathecal morphine preconditioning on the expression of nerve growth factor (NGF) in the dorsal root ganglia (DRG) in a rat model of myocardial ischemia-reperfusion (I/R). Methods Thirty healthy adult male Sprague-Dawley rats in which intrathecal catheters were successfully placed without complications, weighing 250-350 g, were randomly divided into 5 groups (n=6 each) using a random number table: sham operation group (S group), I/R group, intrathecal morphine preconditioning group (ITMP group), μ receptor antagonist CTOP + intrathecal morphine preconditioning group (CTOP + ITMP group), and CTOP control group (CTOP group). Myocardial ischemia was induced by 30 min of occlusion of the anterior descending branch of the left coronary artery followed by 120 min of reperfusion in all the groups except S group.Intrathecal morphine preconditioning was produced by 3 cycles of 5 min intrathecal injection of morphine 3 μg/kg (10 μl) at 5 min intervals within 30 min before ischemia in ITMP group.In CTOP+ ITMP and CTOP groups, 1 μg/μl CTOP 10 μl was injected intrathecally at 10 min before morphine preconditioning and 40 min before ischemia, respectively.At 120 min of reperfusion, the rats were sacrificed, and myocardial specimens were obtained for determination of myocardial infarct size, and DRGs were removed for determination of the expression of NGF by using immunohistochemistry and Western blot. Results Compared with S group, the myocardial infarct size was significantly increased, and the expression of NGF in DRGs was significantly up-regulated in I/R group (P 0.05). Compared with ITMP group, the myocardial infarct size was significantly increased, and the expression of NGF in DRGs was significantly up-regulated in CTOP+ ITMP and CTOP groups (P<0.05). Conclusion The mechanism by which intrathecal morphine preconditioning reduces myocardial I/R injury is related to activation of spinal μ receptors, inhibition of NGF expression in DRGs, and reduction of responses to noxious stimulation in the rats. Key words: Morphine; Injection, spinal; Ischemic preconditioning; Nerve growth factor; Myocardial reperfusion injury; Ganglia, spinal