Behavioral evidence supporting a differential role for spinal group I and II metabotropic glutamate receptors in inflammatory hyperalgesia in sheep

• Published in: Neuropharmacology Vol. 43; no. 3; pp. 319 - 326
• Main Authors: Dolan, S., Nolan, A.M.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.09.2002; Elsevier
• Subjects: Amino Acids, Dicarboxylic - pharmacology; Analgesia; Analgesics; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Carrageenan; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - therapeutic use; Glutamatergic system (aspartate and other excitatory aminoacids); Glutamates - pharmacology; Hyperalgesia - physiopathology; Hyperalgesia - psychology; Indans - pharmacology; Inflammation; Inflammation - chemically induced; Inflammation - physiopathology; Injections, Spinal; Medical sciences; Metabotropic glutamate receptors; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Nociceptors - drug effects; Pain Threshold - drug effects; Pharmacology. Drug treatments; Physical Stimulation; Receptors, Metabotropic Glutamate - agonists; Receptors, Metabotropic Glutamate - antagonists & inhibitors; Receptors, Metabotropic Glutamate - physiology; Sheep; Spinal cord; Spinal Cord - physiopathology; Metabotropic glutamate receptors; Analgesia; Spinal cord; Inflammation; Carrageenan; Nociception; Group I mglu glutamate receptor; Treatment efficiency; Central nervous system; Intrathecal administration; Metabotropic glutamate receptors: Carrageenan; Group II mglu glutamate receptor; Hyperalgesia; Prevention; Vertebrata; Mammalia; Analgesic; Treatment; Animal; Sheep; Artiodactyla; Antagonist; Mechanism of action; Ungulata; Chemical stimulus
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/S0028-3908(02)00107-7

A differential role for metabotropic glutamate receptors (mGluRs) in spinal nociception in normal animals has previously been identified. The present study examined the contribution of group I and group II mGluRs to the development and maintenance of inflammatory hyperalgesia produced by unilateral intradermal injection of carrageenan into the lower forelimb in sheep. Carrageenan (7.5 mg in 500 μl) produced a significant bilateral reduction in forelimb mechanical withdrawal thresholds. Intrathecal administration of saline-vehicle or the group II mGluR antagonist (2S)-α-ethylglutamate (EGLU; 570 nmol) had no effect on either the development or maintenance of hyperalgesia. However, intrathecal administration of the group I mGluR antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 450 nmol) before carrageenan blocked the development of ipsilateral hyperalgesia, and when given 2 h after carrageenan, reversed both ipsilateral and contralateral hyperalgesia. Intrathecal administration of the group II mGluR agonist (2S,1S,2S)-2-(carboxycyclopropyl)glycine (L-CCG-I; 620 nmol) given either before or after carrageenan treatment produced analgesia and anti-hyperalgesia, an effect abolished by co-administration of EGLU (570 nmol). The magnitude of the analgesic response, assessed by the area under the response curve, was significantly greater than that produced by LCCG-I in normal animals. These data demonstrate that the development and maintenance of inflammatory hyperalgesia is dependent on activation of group I mGluRs in spinal cord. In addition, the analgesic and anti-hyperalgesic actions of group II mGluRs suggest that these receptors play a crucial role in modulating acute inflammatory hyperalgesia.