The present study was performed to explore the effect of calcitonin gene-related peptide (CGRP) and its antagonist CGRP8-37 on the evoked discharge frequency of wide dynamic range (WDR) neurons in the dorsal horn of the spinal cord in rats. Recording was performed with a multibarrelled glass micropipette and the chemicals were delivered by iontophoresis. The discharge of WDR neurons was evoked by transdermic electrical stimulation applied on the ipsilateral hindpaw. (1) Iontophoretic application of CGRP at an ejectioncurrent of 100nA increased the discharge frequency of WDR neurons significantly. (2) Iontophoretic application of CGRP8-37 at an ejection current of 80 or 160nA induced significant decreases in the discharge frequency of WDR neurons, but not at 40nA. (3) Iontophoretic application of CGRP8-37 not only antagonized the CGRP-induced increase in the evoked discharge frequency of WDR neurons but also induced a significant decrease in the evoked discharge frequency of WDR neurons compared to basal levels. The results indicate that CGRP and its receptors play a facilitary role on the transmission and/or modulation of nociceptive information in the dorsal horn of the spinal cord in rats.

The present study investigated the effect of diazepam binding inhibitor (DBI) on nociception in the central nervous system of rats. There were dose-dependent increases in hindpaw withdrawal latency (HWL) to noxious thermal and mechanical stimulation after intrathecal injection of 1, 5 or 10μg of DBI in rats, indicating a DBI-induced anti-nociceptive effect at the spinal levels of rats. Furthermore, it was found that there were no significant influences of intrathecal co-administration of γ-aminobutyric acid (GABA) on the intrathecal DBI-induced increases in HWLs of rats. Intracerebroventricular administration of 1, 10 or 20μg of DBI also induced dose-dependent increases in HWL to thermal and mechanical stimulation in rats, suggesting an anti-nociceptive effect of DBI in the brain. Moreover, there were no significant influences of intracerebroventricular co-administration of 2μg of GABA on the intracerebroventricular DBI-induced increases in HWL of rats. The results of the present study demonstrated that DBI played anti-nociceptive effects in the central nervous system of rats.

The present study was performed in rats with experimentally induced mononeuropathy after left common sciatic nerve ligation. The hindpaw withdrawal latencies to thermal and mechanical stimulation increased significantly after intra-periaqueductal grey injection of 2 or 3nmol, but not 1nmol of galanin in rats with mononeuropathy. Intraperitoneal administration of 4.5mg/kg morphine induced significant increases in hindpaw withdrawal latencies to both noxious stimulation, which were attenuated by following intra-periaqueductal grey injection of 2nmol of the galanin antagonist galantide. Furthermore, the antinociceptive effect induced by intra-periaqueductal grey injection of 26.6nmol of morphine was attenuated significantly by following intra-periaqueductal gray administration of 2nmol of galantide. The results demonstrated that in periaqueductal grey galanin plays an antinociceptive role in rats with mononeuropathy and galanin is involved in the mechanisms of opioid-induced antinociception.

The present study was performed to explore the involvement of opioid receptors in the calcitonin gene-related peptide 8-37 (CGRP8-37, an antagonist of CGRP receptor)-induced inhibition of the activity of widedynamic-range (WDR) neurons in the spinal dorsal horn of rats. Extracellular recording was performed with a multibarrelled glass micropipette, and the chemicals were delivered by micro-iontophoresis. The discharge frequency of WDR neurons was evoked by subcutaneous electrical stimulation applied to the ipsilateral hindpaw. Iontophoretic application of CGRP8-37 by an ejection current of 160nA induced significant inhibition of the discharge frequency of WDR neurons. The inhibitory effect of CGRP8-37 on the activity of WDR neurons was attenuated by later iontophoretic application of the opioid antagonist naloxone. Furthermore, the effect of CGRP8-37 was attenuated by either iontophoretic application of the kappa-receptor antagonist norbinaltorphimine (nor-BNI) or the mu-receptor antagonist β-funaltrexamine (β-FNA) but not by the delta-receptor antagonist naltrindole. The results indicate that kappaand mu-opioid receptors on the membrane of WDR neurons are involved in the modulation of CGRP8-37-induced antinociception in dorsal horn of the spinal cord in rats.