ABSTRACT
Several lines of evidence indicate that Group I metabotropic glutamate (mGlu) 1alpha 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 mGlu1alpha receptors in peripheral nociception. To accomplish this we investigate the presence of mGlu1alpha 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 mGluR1alpha 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 mGlu1alpha 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 microM AIDA+2% formalin significantly attenuates phase 2 lifting/licking and flinching behavior and this AIDA-induced effect is blocked with co-injection of 1 microM 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 mGlu1alpha receptors are present on peripheral cutaneous axons and activation of peripheral mGlu1alpha receptors contributes to mechanical allodynia and inflammatory pain but not thermal hyperalgesia.
Subject(s)
Ganglia, Spinal/metabolism , Nerve Fibers/metabolism , Neurons, Afferent/metabolism , Nociceptors/metabolism , Pain/metabolism , Receptors, Metabotropic Glutamate/metabolism , Thermosensing/physiology , Animals , Dose-Response Relationship, Drug , Drug Interactions/physiology , Excitatory Amino Acid Agonists/pharmacology , Excitatory Amino Acid Antagonists/pharmacology , Ganglia, Spinal/drug effects , Ganglia, Spinal/ultrastructure , Glycine/analogs & derivatives , Glycine/pharmacology , Immunohistochemistry , Indans/pharmacology , Inflammation/metabolism , Male , Microscopy, Electron , Nerve Fibers/drug effects , Nerve Fibers/ultrastructure , Neurons, Afferent/drug effects , Neurons, Afferent/ultrastructure , Nociceptors/drug effects , Nociceptors/ultrastructure , Pain Measurement/drug effects , Physical Stimulation , Rats , Rats, Sprague-Dawley , Receptors, Metabotropic Glutamate/drug effects , Resorcinols/pharmacology , Signal Transduction/drug effects , Signal Transduction/physiology , Skin/innervation , Thermosensing/drug effectsABSTRACT
This study focused on expression of estradiol receptors (ER) during the estrous cycle. Labeling for ERalpha or beta antigens and luteinizing hormone (LH) or follicle-stimulating hormone (FSH) beta-subunits was done on freshly dispersed pituitary cells. The lowest expression of ERalpha and beta was seen in estrus (23% and 12%, respectively). Expression increased to 42-54% of pituitary cells by diestrus. In males, cells with ERalpha or beta were 37% or 20% of the population, respectively. ERalpha or beta and gonadotropin antigens were in 6-9% of pituitary cells from male rats. Early in the cycle (estrus and metestrus), less than 5% of pituitary cells expressed ERalpha or beta with gonadotropins. These values doubled to reach a peak of 10% during proestrus (just before ovulation). These data show that a rise in expression of both ERalpha and ERbeta is a part of preovulatory differentiation of pituitary gonadotropes.(J Histochem Cytochem 49:665-666, 2001)
