Involvement of opioid receptors in the CGRP8‐37‐induced inhibition of the activity of wide‐dynamic‐range neurons in the spinal dorsal horn of rats

Abstract

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 wide-dynamic-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 160 nA 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 nor-binaltorphimine (nor-BNI) or the mu-receptor antagonist beta-funaltrexamine (beta-FNA) but not by the delta-receptor antagonist naltrindole. The results indicate that kappa- and 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.

Roles of calcitonin gene-related peptide and its receptors in pain-related behavioral responses in the central nervous system

“…In addition, they demonstrate that CGRP8-37 antagonizes the CGRP-induced increase inactivity of WDR neurons, suggesting the effect of CGRP is mediated by CGRP receptor 1 . These results demonstrate that CGRP and its receptors are involved in the transmission and modulation of nociceptive information in dorsal horn of the spinal cord (Yu et al, 1999Yan and Yu, 2004). Interestingly, Yu et al (2002) further find that CGRP8-37 alone induces a significant inhibition on the activity of WDR neurons.…”

“…Further study demonstrate that after administration of CGRP8-37, the antagonist of CGRP receptor 1, to the dorsal surface of spinal cord from L3 to L5, the activity of WDR neurons decrease significantly, the effect last more than 30 min (Yu et al, 1999;Yan and Yu, 2004). These results strongly indicate the inhibitory effects of CGRP8-37 on the transmission and modulation of pain information in the spinal cord.…”

“…Intrathecal CGRP Mechanical nociception (Oku et al, 1987;Sun et al, 2004) No effects (Jolicoeur et al, 1992;Yu et al, 1994) CGRP8-37 Antinociceptive effects in normal animal (Yu et al, 1994(Yu et al, , 1995 Antinociceptive effects in inflammation pain animal (Salmon et al, 2001;Yu et al, 1996a) Antinociceptive effects in neuropathical pain animal (Yu et al, 1996b) Dorsal horn neurons CGRP Excitatory effects on neuronal activity (Leem et al, 2001;Neugebauer et al, 1996;Sun et al, 2004;Yu et al, 2002) CGRP8-37 Inhibitory effects on neuronal activity (Neugebauer et al, 1996;Yan and Yu, 2004;Yu et al, 1999) Brain PAG CGRP Antinociceptive effects in normal animal Antinociceptive effects in neuropathical pain animal (Xu et al, 2000) CGRP8-37 No effects alone, block CGRP-induced antinociception in normal animal No effects alone, block CGRP-induced antinociception in neuropathical pain animal (Xu et al, 2000) NRM CGRP Antinociceptive effects in normal animal (Huang et al, 2000) CGRP8-37…”

Effect of Continuous Passive Motion Initiated After the Onset of Arthritis on Inflammation and Secondary Hyperalgesia in Rats

“…Although the CGRP expression intensity in the deep layer (laminae III-VI) of L2-3 was significantly higher in the IM and CPM groups compared to the control group, there were no significant differences between these two treatment groups. It is known that CGRP increases the discharge frequency of WDR neurons in the dorsal horn, which is blocked by the CGRP receptor antagonist CGRP8-37 (Yan and Yu 2004). This indicates that increased CGRP expression in the spinal dorsal horn reduces the pain threshold through activation of WDR neurons, which are distributed in the deep layer of the spinal dorsal horn.…”

Locomotor Dysfunction and Pain: The Scylla and Charybdis of Fiber Sprouting After Spinal Cord Injury

“…CGRP colocalizes with substance P in small-diameter afferent fibers [73,74] and is released following noxious peripheral stimulation [75] and/or inflammation [50,51,76]. CGRP release results in direct enhancement of dorsal horn nociceptive neuron excitability [77][78][79] and nociceptive behaviors [80,81]. Substance P also plays an important role in feed-forward inhibitory activity in the spinal cord, whereby behavioral sensitization can occur if substance P-driven feed-forward signaling is compromised [82,83].…”