Individual differences in sensitivity to pain and analgesia are well appreciated, and increasing evidence has pointed towards a role of inherited genetic factors in explaining some proportion of such variability. It has long been known by practitioners of acupuncture, an ancient modality of analgesia, that some patients are responders' and others `non-responders.' The present research was aimed at de

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

The large, medium-sized, and small neurons of the dorsal root ganglion (DRG) have different functions in the processing of various senses. Hyperpolarization-activated, cyclic nucleotide-gated channels (HCN) contribute greatly to neuronal excitability. In the present study, which used whole-cell patch clamp techniques and immunohistochemical staining methods, the electrophysiological properties of DRG neurons were systematically compared, and the roles of HCN-1, -2, and -4 were examined. The main results were as follows. 1) The large neurons had significantly higher V0.5 values (membranepotential at which the HCN channels were half-activated) and shorter time constants (HCN) than small or mediumsized DRG neurons. However, large DRG neurons had higher Ih density (HCN neuron current). 2) HCN-1 was found predominantly, but not exclusively, in large and medium-sized DRG neurons; HCN-2 was found in all DRG neurons; and HCN-4 was poorly visualized in all DRG neurons. HCN-1 and HCN-2 were colocalized in large and medium-sized neurons with immunostaining of adjacent sections. In the dorsal horn of the spinal cord, HCN-1, HCN-2, and HCN-4 were all expressed in laminae I-IV, although HCN-1 was not detectable in lamina II. 3) Blockade of Ih current in DRG neurons caused a signi ficant decrease in V0.5, resting membrane potential, and repetitive firing number of action potential and a significant increase in time of rising phase of action potential. These results suggest that the different HCN channels in the three types of DRG neurons might contribute to their differential electrophysiological properties.

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