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

Nocistatin (NST) and nociception/orphanin FQ (OFQ) are peptides derived from the same precursor that play opposing roles in pain modulation. OFQ antagonizes morphine analgesia and electroacupuncture (EA)-induced antinociceptive effect. The present study investigates whether NST potentiates EA-induced antinociceptive effect and reverses chronic tolerance to EA in mice. Injection of NST (0.5, 5.0 and 50.0ng) intracerebroventricularly had no effect on basal thermal latency, but produced a dose-ependent potentiation of EA-induced antinociceptive effect in mice with the maximum response at 5.0ng. NST (5.0ng) partly reversed chronic tolerance to EA. These results suggest that NST in the brain might play roles in EA-induced antinociceptive effect and the development of chronic tolerance to EA in mice.

Our previous studies have shown that 100Hz electroacupuncture (EA) produced antinociception through the release of endogenous opioids (mainly dynorphin) and the activated -opioid receptors in normal rats. Acupuncture is an effective treatment in relieving pain, but it develops tolerance after epeated administration. It has been reported that N-methyl-d-aspartate (NMDA) receptor antagonists could increase the antinociceptive effects induced by morphine and delay the development of tolerance to morphine but nothing has yet been described to reduce EA tolerance. Here we test whether ketamine, a non-competitive NMDA receptor antagonist, would enhance 100Hz EA antinociception as well as prevent or delay the development of chronic tolerance to 100Hz EA in normal rats. The results are as follows: (1) ketamine injected intraperitoneally (i.p.) 15min prior to EA enhanced the antinociceptive effects of 100 Hz EA at a dose of 5.0mg/kg, but not 0.2 or 1.0mg/kg. However, ketamine at either dose did not affect the basal nociceptive threshold (represented by tail-flick latency). (2) Ketamine at a dose of 5.0mg/kg delayed the development of chronic tolerance to 100Hz EA antinociception. We conclude that ketamine can enhance antinociception of 100Hz EA and delay the tolerance to 100Hz EA in rats. These results suggest that the development of 100Hz EA tolerance to antinociception was mediated, at least in part, through peripheral NMDA receptors, which may be useful in improving the therapeutic effects of EA in the treatment of pain when EA tolerance occurs.

The present study was conducted to evaluate the characteristics of electroacupuncture (EA)-induced analgesia in mice. Three inbred strains of mice (DBA/2, C57BL/6J, BALB/c) and three outbred strains (ICR, LACA, NIH) were used in the experiment. Two pairs of metallic needles were inserted into acupoints ST 36 and SP 6 connected to an electric pulse generator. EA parameters were set as constant current output with alteration of a positive and negative square wave, 0.6ms in pulse width for 2Hz and 0.3ms for 100Hz. Tail-flick latencies evoked by radiant heat were measured before, during and after EA stimulation. We found that (1) DBA/2 mice showed a significantly more potent analgesic effect than the other five strains in response to both 100 and 2Hz EA. In this case, the intensities were 1.0-2.0-2.0mA, 10 min for each intensity totally 30min. (2) EA analgesia increased as the intensity of stimulation increased from 0.5 to 21 2.0mA, but it remained at this plateau when the intensity further increased from 2.0 to 3.0mA. (3) 10.0mg?kg naloxone was needed to 21 block the analgesic effect induced by 2Hz EA of 2.0mA, but to block that by 100Hz, 25.0mg?kg was necessary. (4) A positive 21 correlation was observed between analgesia induced by morphine at the dose of 5.0mg?kg and by 100Hz EA in two tested strains DBA/2 and C57BL/6J. In conclusion, EA induces reliable, strain-dependent analgesia in mice. The naloxone-reversibility of EA, a measure of whether it is opioid or non-opioid mediated, is dependent upon intensity and frequency.

The protective effects of adenovirus-mediated glia cell linederived neurotrophic factor (GDNF) gene transaction was investigated on cultured motoneurons. First, the dose