Effect of diabetes on baclofen-induced inhibition of mEPSCs in spinal glutamatergic neurons in rats with neuropathic pain

Objective To evaluate the effect of diabetes on baclofen-induced inhibition of miniature excitatory postsynaptic currents (mEPSCs) in spinal glutamatergic neurons in rats with neuropathic pain.Methods Thirty male Sprague-Dawley rats,aged 4 weeks,weighing 150-170 g,were randomly divided into 2 groups (n＝15 each group):control group (C group) and diabetic neuropathic pain group (D group).Diabetic neuropathic pain was induced by intraperitoneal injection of streptozotocin 50 mg/kg and confirmed 28 days later by blood glucose ＞ 16.7 mmol/L and pain threshold ＜ 4 g in group D,while the rats received the equal volume of normal saline in C group.The animals were anesthetized with intraperitoneal 10％ chloral hydrate 50 mg/kg.The rats were then sacrificed and lumbar segments (L1.5) of the spinal cord were removed for slice preparations.Glutamatergic mEPSCs in lamina Ⅱ neurons were recorded by using whole-cell patch-clamp technique and 20 neurons located in lamina Ⅱ of the spinal cord were recorded in each group.The cells stabilized for 30 min after sealing,and then baclofen with the final concentrations of 1,10,20,50 μmol/L was added to the perfusion solution at 5 min intervals followed by washout.The frequency and intensity of glutamatergic mEPSCs were recorded immediately before and after administration and at 5 min after washout.The inhibitory effect of baclofen on glutamatergic mEPSCs was measured and the inhibitory rate was calculated.Results Compared with group C,the frequency of glutamatergic mEPSCs was significantly increased and the inhibitory rate was decreased under each concentration (P ＜ 0.05),and no significant change was found in the intensity of mEPSCs under each concentration in D group (P ＞ 0.05).Conclusion Diabetes decreases baclofen-induced analgesic effect in rats with neuropathic pain,which is related to inhibition of mEPSCs in spinal glutamatergic neurons. Key words: Diabetes mellitus ;  Baclofen ;  Neuralgia ;  Glutamic acid ;  Excitatory postsynaptic potentials ;  Spinal cord ;  Neurons