Effect Of L-tetrahydropalmatine On Spontaneous Activities Of Injured Dorsal Root Ganglion Neurons In Rats And Its Mechanism

Peripheral nerve injury induced by mechanical trauma,ischemia,toxicosis, 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. Although many treatment of chronic pain which caused by disc prolapse, the effects are not the same. So it becomes the important task to explore the pathogenesis of neuropathic pain and develop the new analgesic. It is considered that traditional chinese medicine can give full play in treatment chronic pain.dl-Tetrahydropalmatine (dl-THP), an active principle isolated from Corydalis, the analgesic mechanism of l-THP as"Huoxuexingqi"in Traditional Chinese Medicine theories. At present, pharmacological effects consider l-THP can block the central dopamine (DA) receptors, and its analgesic effect is weaker than dolantin, but much stronger than general antipyretic analgesics, and much better for chronic persistent pain. After nerve injury, abnormal spontaneous discharges generated in injured sensory nerve axons and sensitize dorsal horn neurons and induce the chronic pain symptom. So, we attempt to observe the impossible of l-THP inhibit the generation of chronic pain signals after nerve injury. In addition, to explore the mechanism and target of l-THP would help to enhance the pertinence of l-THP in chronic pain treatment and provide the foundation for l-THP acting as a peripheral analgetic.The present study was performed on model of chronically compressed rat DRG through the single fiber in vivo and on the persistent sodium current (I_Nap) through patch-clamp. We observed and analyzed the effect of l-THP on A-fiber ectopic spontaneous discharges from injured DRG, to ascertain whether l-THP affects the peripheral nervous system.ResultsThe first part: The types of chronic compressed DRG neurons(1) Periodic activity characterized by the interspike intervals that appeared repeatedly at regular intervals, 32% (27/84) of the total number of spontaneous units fell into this category.(2) Non-periodic activity characterized by an irregular pattern of the interspike intervals 18% (15/84).(3) Bursting activity characterized by bursts separated by silent periods 50 %( 42/84)The second part: Responses of injured DRG neurons with different firing patterns to l-THP.Ectopic spontaneous discharges were responsive to l-THP applied around the injured DRGs for 5min.(1) l-THP had no effect on 89 %( 24/27) of the neurons with periodic activities.(2)l-THP had the effect on 66.7%(10/15) of the neurons showing non-periodic discharge(3)l-THP had the effect on 74%(31/42) bursting discharge were responsive tol-THP (150μM).The third part: l-THP decreased discharge rate in injured DRG neurons with a dose-response relationship.The responses of non-periodic firing neurons to l-THP with different concentrations and each concentrations of l-THP for 5 minute. l-THP decreased discharge rate in injured DRG neurons with a dose-response relationship at concentrations ranging from 10μmol/L to 150μmol/L. The mean firing rate decreased as the dose of l-THP increased.The fourth part: The inhibitory effect of l-THP on the ectopic discharges.Whatever effect l-THP had on the neurons, the firing rates in most cases 59%(26/44)returned to pre application levels within 20min washout after the delivery of l-THP . In contrast, for the remaining 41 %( 18/44) neurons, spontaneous activity did not resume within 3h after washout. However each of them showed an excitatory response to perfused Ca2+-free ACSF, indicating that all of them were alive.The fifth party: The inhibitory effect of l-THP on I Nap.When adding 10μmol/L l-THP, the current value decreased. When washing out l-THP, the current recovered, indicating that l-THP could inhabit the I Nap. Main conclusions:(1) Our study has provided further evidence that there are three types of ectopic spontaneous discharges from injured A-type DRG. They are period rhythm, non-period rhythm, bursting rhythm. (2) l-THP could inhibit most spontaneous activities of CCD which suggests that l-THP may inhibit the conduction of a chronic pain signal.(3)The effects of l-THP on a spontaneous active unit were increasing with the concentration of l-THP increased and dose-dependent relationship for the effect of l-THP.(4)l-THP may inhibit the spontaneous discharges of neurons through inhibiting the persistent sodium current of DRG neurons.