QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.104.073817v1 312/1/120    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, S.-R. Articles by Pan, H.-L. Search for Related Content PubMed PubMed Citation Articles by Chen, S.-R. Articles by Pan, H.-L.

NEUROPHARMACOLOGY

Distinct Roles of Group III Metabotropic Glutamate Receptors in Control of Nociception and Dorsal Horn Neurons in Normal and Nerve-Injured Rats

Departments of Anesthesiology (S.-R.C., H.-L.P.) and Neural and Behavioral Sciences (H.-L.P.), Pennsylvania State University College of Medicine, Hershey, Pennsylvania

Increased glutamatergic input to spinal dorsal horn neurons constitutes an important mechanism for neuropathic pain. However, the role of group III metabotropic glutamate receptors (mGluRs) in regulation of nociception and dorsal horn neurons in normal and neuropathic pain conditions is not fully known. In this study, we determined the effect of the group III mGluR specific agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4) on nociception and dorsal horn projection neurons in normal rats and a rat model of neuropathic pain. Tactile allodynia was induced by ligation of L5/L6 left spinal nerves in rats. Allodynia was determined by von Frey filaments in nerve-injured rats. The nociceptive threshold was tested using a radiant heat and a Randall-Selitto pressure device in normal rats. Single-unit activity of ascending dorsal horn neurons was recorded from the lumbar spinal cord in anesthetized rats. An intrathecal (5–30 µg) L-AP4 dose-dependently attenuated allodynia in nerve-injured rats but had no antinociceptive effect in normal rats. Topical spinal application of 5 to 50 µM L-AP4 also significantly inhibited the evoked responses of ascending dorsal horn neurons in nerve-ligated but not normal rats. Furthermore, blockade of spinal group III mGluRs significantly decreased the withdrawal threshold and increased the evoked responses of dorsal horn neurons in normal but not nerve-injured rats. These data suggest that group III mGluRs play distinct roles in regulation of nociception and dorsal horn neurons in normal and neuropathic pain states. Activation of spinal group III mGluRs suppresses allodynia and inhibits the hypersensitivity of dorsal horn projection neurons associated with neuropathic pain.

Address correspondence to: Dr. Hui-Lin Pan, Department of Anesthesiology, H187, Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033. E-mail: hpan{at}psu.edu

This article has been cited by other articles:

				H.-Y. Zhou, H.-M. Zhang, S.-R. Chen, and H.-L. Pan Increased Nociceptive Input Rapidly Modulates Spinal GABAergic Transmission Through Endogenously Released Glutamate J Neurophysiol, January 1, 2007; 97(1): 871 - 882. [Abstract] [Full Text] [PDF]