Suppression of neuropathic pain by peripheral electrical stimulation in rats: mu-opioid receptor and NMDA receptor implicated.

Peripheral electrical stimulation (PES) has been utilized to manage chronic pain associated with nerve injury. However, the data on clinical effectiveness are conflicting and the neurophysiological mechanism is not well known. This study was designed to assess whether PES relieved neuropathic pain and its possible mechanisms. The neuropathic pain model was made with lumbar 5th (L5) and 6th (L6) spinal nerve ligations in rats. Nociceptive responses of the rats were assessed by the cold plate test (the number and duration of paw lifts that occurred in 5 min on a 5 +/- 1 degrees C cold plate). PES with a frequency of 2 Hz and at increasing strengths was given for 30 min via stainless-steel needles inserted into standard acupoints on the leg and back, respectively. Immunochemistry was used to examine the immunoreactivity of the NMDA receptor 1 (NR1) subunit in the spinal cord dorsal horn. The results are as follows: (1) PES relieved neuropathic pain and the effect was blocked by 1.0 mg/kg naloxone. (2) The effect of one session of PES lasted up to 12 h. (3) Repetitive PES showed a cumulative effect and no tolerance was observed. (4) There was a significant increase of NR1 immunoreactivity in the superficial laminae of the spinal cord of neuropathic pain rats as compared with naive rats. This increase could be reversed by repetitive 2 Hz PES. These results suggest that PES can relieve neuropathic pain, and that mu-opioid receptors and NMDA receptors are involved in the effect of PES.

The role of calcitonin gene-related peptide (CGRP) in the generation and maintenance of mechanical allodynia and hyperalgesia in rats after intradermal injection of capsaicin.

This study was designed to assess the role of calcitonin gene-related peptide (CGRP) and its receptor in the generation and maintenance of secondary mechanical allodynia and hyperalgesia induced by intradermal injection of capsaicin in rats. Paw withdrawal responses (PWRs) to von Frey hairs with different bending forces applied on the rat paw were tested in this study. CGRP(8-37), a specific antagonist of CGRP 1 receptors, was delivered through a microdialysis fiber inserted across the dorsal horn. Post- and pretreatment paradigms were followed. When CGRP(8-37) was administered 1h after capsaicin injection, the mechanical allodynia and hyperalgesia were partially reversed in a dose-dependent manner. On the other hand, when rats were treated with CGRP(8-37) prior to capsaicin injection, the PWRs to von Frey applications were significantly reduced as compared to control animals. Collectively, these results suggest that CGRP receptors present in the dorsal horn are involved in the generation and maintenance of nociceptive behaviors associated with cutaneous inflammation.

[Effect of electroacupuncture with different frequencies on neuropathic pain in a rat model].

AIM: Our previous studies showed that electroacupuncture (EA) could inhibited radiant heat induced pain and acute or chronic inflammatory pain in rats. In the present study, we observed whether EA with different frequencies could suppress neuropathic pain. METHODS: L5/L6 nerve ligation model was used to assess the effect of EA on neuropathic pain. Mechanical allodynia was represented by 50% withdrawal threshold, while cold-induced ongoing pain was detected by the number of paw lift in 5 min when the rat was put on a 5 degrees cold plate. Han's acupoint nerve stimulator (HANS) was connected to needles inserted into acupoints "jiaji" and "Zusanli" in both sides. The parameters were: (intensity: 0.5-1-2 mA, 10 min each; frequency 2 Hz or 100 Hz; pulse width: 0.6 ms for 2 Hz, 0.2 ms for 100 Hz). RESULTS: EA of both 2 Hz and 100 Hz could relieve the mechanical allodynia, where 2 Hz could induce the effect with shorter latency; they could also relieve the cold-induced ongoing pain, where the effect of 2 Hz outlasted the EA session by up to 48 h after repetitive stimulations over several weeks; a significant relieving effect on cold-induced ongoing pain could also be induced by needle insertion without stimulation. CONCLUSION: EA could relieve neuropathic pain, the analgesic effect of 2 Hz EA is higher than 100 Hz EA.