It is widely accepted that ectopic discharges originated from injured sites and dorsal root ganglion (DRG) neurons after peripheral nerve injury contribute to neuropathic pain. However, it has been recently shown that ectopic discharges were not always necessary for neuropathic pain. In the present study, we aim to further examine the role of ectopic discharges in neuropathic pain in a spinal nerve ligation (SNL) model. With teased fiber recordings in vivo, the characteristics of ectopic discharges were observed over 14 days after SNL, and the correlation between ectopic discharges and tactile allodynia was analyzed. It was observed that ectopic discharges have three firing patterns (tonic, bursting, and irregular) after SNL, and proportions of these three patterns changed dynamically over time. The tonic and bursting types were dominant in the first 24h following SNL, while the irregular type became the only pattern in the late stage (day14). The average frequencies of ectopic discharges and the percentage of active filaments also changed over time, reaching the peak 24h after SNL and then declined gradually. Ectopic discharges were highly correlated with tactile allodynia in the first 24h following SNL, but surprisingly, not in the late stage of days 1 to 14. These findings suggest that ectopic discharges may be crucial in the triggering of neuropathic pain in the early stage, but their importance become more limited over time.

Mu-opioid agonists and N-methyl-d-aspartate (NMDA) receptor antagonists have been shown to attenuate mechanical allodynia in neuropathic pain models. We have previously reported that 2Hz ectroacupuncture (EA) produced analgesia via releasing endogenous opioid peptides (i.e.-endorphin and endomorphin) and the activated-opioid receptors. The present study aimed to examine whether ketamine, an NMDAreceptor antagonist, can enhance the anti-allodynic effects induced by 2 HzEAin a rat model of neuropathic pain following spinal nerve ligation (SNL). The results are as follows: (1) EA itself or i.p. injection of ketamine reduced mechanical allodynia (i.e.increase in withdrawal threshold). (2) Although injection of ketamine at a low dose (1.0mg/kg) alone did not influence mechanical withdrawal threshold, combination of ketamine at this dose with EA produced more potent anti-allodynic effect than that induced by EA alone. (3) The anti-allodynic effect of EA combined with ketamine could be reversed by i.p. injection of naloxone (2.0mg/kg). These results suggested that ketamine potentiate the anti-allodynic of EA in rats with spinal nerve ligation, and endogenous opioid system is likely to be involved in this process.

The present study aimed to systematically observe the change of vanilloidreceptor1 (VR1) during in

Peripheral nerve injury causes ectopic discharges of different firing patterns, which may play an important role in the development of neuropathic pain. The molecular mechanisms underlying the generation of ectopic discharges are still unclear. In the present study, by using in vivo teased fiber recording technique we examined the effect of ZD7288, a specific blocker of hyperpolarization-activated current (Ih), onthe ectopic discharges in the dorsal root ganglion (DRG) neurons injured by spinal nerve ligation. We found that ectopic discharges of all three firing patterns (tonic, bursting and irregular) were dose- and time-dependently inhibited by local application of ZD7288. Interestingly, the extent of suppression was negatively related to frequency of firing prior to application of ZD7288. We also observed that ZD7288 could alter the firing patterns of the ectopic discharges. At 100AM, tonic firing pattern was gradually transformed into bursting type whereas at 1 mM, it could be transformed to integer multiples firing. These results indicate that Ih might play a role in the generation of various forms of ectopic discharges in the injured DRG neurons and may thus be a possible target for neuropathic pain treatment.

The aim of the present study was to assess the e