| Peripheral nerve injury induced by mechanical trauma,ischemia,or local inflammation can lead to chronic pain symptoms,including hyperalgesia,allodynia,spontaneous pain. The sciatic nerve and low back pain are often ascribed to chronic compression of the dorsal root ganglia(DRG) or its spinal root by herniated intervertebral disc,or stenosis of intervertebral foramen.In this case,the excitability of injured neurons within DRG,which is considered as the first stage of the sensory pathway,enhance abnormally,,and those neurons become hyperexcitable.Experiments have documented a variety of changes occurring in injured hyperexcitable neurons,comprising of reduction of the spike rheobase,accommodation, initiation of spontaneous discharges.Thus injured DRG neurons become the pacemaker of neuropathic pain.Subthreshold membrane potential oscillation(SMPO) is the foundment for producing ectopic spontaneons discharges.Then,sensory neurons and nociceptors may develop abnormal responsiveness to sympathetic agonists and the activation of postganglionic sympathetic efferent axons in certain neuropathic pain state after tissue inflammation and nerve lesion.Norepinephrine(NE) have certain enhancement effect on this ectopic spontaneous discharges in intro and subthreshold membrane potential oscillation mediates the exciatory effect of norepinephrine in chronically compressed dorsal root ganglion neurons in the rat. however, the ion channelmechanism is still not very clear for norepinephrine contributing on SMPO,limiting the further study of mechanism for the chronic pain.To utilize the hyperexcitable speciments in the neurons of chronically compressed DRG. Through electrophysiological detection for whole-cell pach clamp of single cell in injured DRG neurons in intro, we aim to elucidate the ion mechanism of NE contributing on SMPO.This will help to make clear of the reason of why the pacemaker of chronic pain formed. So can supply a new therapy strategy for chornic pain.Experiment results 1 .Detection of the persistent sodium current(INap) in injured DRG neuronsAccording to the biological features of persistent sodium channel:(1) activation potential is lower than the transient sodium channel ,about 10— 15mV negative to the transient sodium current.(2) the time of the channel activation is longer, that is inactivation course is slow. (3) as the channel opening,the amplitude of the current is lower. (4) the high sensitive to TTX. A total of 106 neurons from 48 chronic compressed DRGs were recorded, there are 10 (D>40um) big cells and 85 the middle size cells(D=3040um) and 11 the small cells(2530um) between them. After blest sealed in patch-clamp, stimulus in ramp wave (from -80mV to -30mV, time 3s), recording in perforated whole-cell pach clamp. The current is different according to the cell size,the big cells have the bigger current. The activation potential of middle size cells is about -70mV, and the most biggest current showed at -55 mV, the averge amplitude is 150±40 pA.The opening time is almost alike, the middle cell is 180±20 ms,the small is 165±15 ms,the averge time is 150—200 ms. 2.The persistent current is sensitive to TTXThe detected persistent current is high sensitive to the low concentration TTX in injured DRG neurons. Usually at 100 nmol/L concentration may be blocked wholey.This illusted that it is a new persistent sodium curret different...
|
PDF Full Text Request