Metabotropic glutamate 1α receptors on peripheral primary afferent fibers: Their role in nociception

Several lines of evidence indicate that Group I metabotropic glutamate (mGlu) 1α receptors are involved in the processing of nociceptive information in the spinal cord. The goals of the present study are to document the role of mGlu1α receptors in peripheral nociception. To accomplish this we investigate the presence of mGlu1α receptors on peripheral primary afferent fibers and determine the behavioral effects of (S)-3,5-dihydroxyphenylglycine (S-DHPG), which is an mGlu1/5 receptor agonist and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA), a selective mGluR1α antagonist, on mechanical and thermal sensitivity and formalin-induced nociceptive behaviors. The anatomical studies at the electron microscopic level demonstrate that 32.4±2.9% of the unmyelinated axons and 21.6±4.7% of the myelinated axons are positively immunostained for mGlu1α receptors. Intraplantar injection of 0.1 or 1 mM S-DHPG results in a significant increase in mechanical sensitivity that persists for more than 60 min and this effect is blocked by co-injection of S-DHPG with 1 mM AIDA. Intraplantar injection of 40 μM AIDA+2% formalin significantly attenuates phase 2 lifting/licking and flinching behavior and this AIDA-induced effect is blocked with co-injection of 1 μM S-DHPG. In behavioral tests, intraplantar S-DHPG (0.1, 1.0, 10 mM) does not change tail flick latencies or paw withdrawal latencies to heat stimulation. These data indicate that mGlu1α receptors are present on peripheral cutaneous axons and activation of peripheral mGlu1α receptors contributes to mechanical allodynia and inflammatory pain but not thermal hyperalgesia.