Mechanisms Of Abnormal Discharges In Primary Nociceptive Neurons In Rat Models Of Neuropathic Pain

Background and objectivesCell electrophoresis is a noninvasive cell-analysis method.Neuronal function depends mainly on the change of membrane potential.Due to the unique electrical characteristics,cell electrophoresis has great potential in the analysis of neurons.Ectopic spontaneous activity in primary nociceptive neurons was found to be responsible for neuropathic pain induced by peripheral nerve injury.Local inflammatory responses in the nerve injury site may up-regulate the expression of membrane proteins such as ion channels and receptors and induced protein aggregation in the neuronal somata.Previous studies showed that large amount of glycocalyx mainly consisting of sialic acid was linked to these membrane proteins.Whether these negatively-charged sialic acids were responsible for the change of membrane potential and caused the ectopic spontaneous activity is still unclear.The present study aimed to investigate the change of electric characteristic of primary nociceptive neurons after peripheral nerve injury with cell electrophoresis.MethodsWe established an experimental platform of cell electrophoresis for neurons.Adult rats were used in this study and randomly distributed into chronic constrict injury(CCI)group or control group.After the CCI model was established and confirmed with behavior testing of pain,the electrophoresis mobility(EPM)of L4-5 DRG neurons in both groups was measured with cell electrophoresis and compared.ResultsThe average EPM of CCI group(n = 96)was 3.57510.147 ?m.cmV-1.s-1,significantly lower than 5.123±0.220 ?m.cmV-1.s-1 in control group(n = 53,p = 0.0044).EPM of small-sized neurons(presumably C-neurons,n = 27)was 3.318 ±0.286?m.cmV-1.s-1,also significantly lower than 5.415±0.467 ?m.cmV-1.s-1 in control group(n=24,p = 0.0003).The result was contrary to expectations.ConclusionWe found that the stronger adhesion of neurons to the inner surface of capillary tube(probably caused by the accumulated membrane proteins)might be responsible for the lower EPM in the CCI neurons.Further studies are needed to clarify the underlying mechanism of ectopic spontaneous activity and improve the neuronal electrophoresis methods.Background and ObjectiveRapid onset of pain(within one hour)could occur after peripheral nerve injuries in clinical practice.However,most studies in neuropathic pain based on animal models have focused on the observations performed at least one day after nerve injury.The exact timing of onset of pain after peripheral nerve injury was unclear.Recently,a study based on modified SNL model reported a rapid onset of pain(within 10 min)after injury to the spinal nerve and the corresponding spontaneous activities and hyperexcitability in the neighboring intact C-neurons.These results could not be explained with local inflammatory responses induced in the injury site.Together with the results from cobra venom model,we postulated that the lost of A-fiber inputs due to nerve injury induced a dis-inhibition of C-fiber activity,therefore resulted in acute neuropathic pain.In accord to this hypothesis,the injury-induced spontaneous activities of C-neurons could be inhibited by a complementary weak electric stimulation to the injured nerve mimicking the A-fiber inputs.However,whether complementary A-fiber strength electric stimulation is able to alleviate the neuropathic pain behavior is still unclear.In the present study,we applied A-fiber strength electric stimulation to the injured nerve in the modified SNL rats,and compare the behaviors with those without electric stimulation.MethodsAdult SD rats were used in this study and randomly divided into the stimulation or control group.Rats in both groups received modified SNL surgery and were implanted with a stimulation electrode.The L5 spinal nerve was transected awake.Rats in the stimulation group received A-fiber strength electric stimulation(10Hz,0.5mA,3min)to the injured nerve immediately after nerve injury,while rats in the control group received no stimuli.Behavioral testing was conducted to compare the differences in pain-related behaviors between these two groups.ResultsIn the stimulation group,spontaneous pain in the ipsilateral hindpaw was significantly lower than those without stimulation as measured from 10 min to 24hrs after SNL.Mechanical hyperalgesia in the ipsilateral hindpaw of the stimulation group was also significantly lower than those without stimulation from 1 hr to 7 days after SNL.ConclusionsAcute neuropathic pain may be evoked by the removal of normal A-fiber inputs after acute nerve injury.Complementary A-fiber stimulation may provide a potential therapeutic strategy for neuropathic pain after peripheral nerve injury.