title: Activation of alpha2-adrenoreceptors suppresses the excitability of C1 spinal neurons having convergent inputs from tooth pulp and superior sagittal sinus in rats.
abstract: The aim of the present study was to test the hypothesis that activation of alpha(2)-adrenoreceptors modulates the excitability of C1 neurons having convergent inputs from both the tooth pulp (TP) and the superior sagittal sinus (SSS), by using the microiontophoretic techniques of drug application and immunohistochemical approaches. Extracellular single-unit recordings were made from 38 C1 neurons responding to electrical stimulation of TP under pentobarbital-anesthetized rats. Seventy-one percent of C1 neurons (27/38) that responded to TP stimulation also responded to electrical stimulation of the SSS. In these neurons, L: -glutamate-evoked C1 neuronal discharge firings were increased in a dose-dependent manner. The mean glutamate-evoked firing rates were dose-dependently inhibited after microiontophoretic application of clonidine (alpha(2)-adrenoreceptor/imidazoline I(1) receptor agonist). The inhibition of glutamate-evoked C1 mean firings by clonidine was antagonized by the co-application of idazoxan (alpha(2)-adrenoreceptor/imidazoline I(2) receptor antagonist), yohimbine (alpha(2)-adrenoreceptor) but not the alpha(1)-adrenoreceptor antagonist, prazosin with affinity for alpha(2B)- and alpha(2C)-adrenoreceptors. The mean spontaneous discharge frequencies were significantly inhibited by the microiontophoretic application of clonidine and this inhibition was reversed by the co-application of idazoxan, yohimbine. Microiontophoresis of clonidine also resulted in a reduction of TP-/SSS-evoked activity and this effect was reversed by the co-application of yohimbine. Immunoreactivity for alpha(2A)-adrenoreceptor was found in the superficial layers of I-III in the C1 region. These results suggest that alpha(2)-adrenoreceptor agonist clonidine inhibits the excitability of C1 neurons having convergent inputs from TP and SSS afferents, and that the activation of alpha(2A)-adrenoreceptors onto C1 dorsal horn neurons may contribute as a useful therapeutic target for the alleviation of trigeminal referred pain associated with migraine and tooth pain.
authors.affiliation: Department of Physiology, School of Dentistry at Tokyo, Nippon Dental University, 1-9-20 Fujimi-cho, Chiyoda-ku, Tokyo, 102-8159, Japan. m-takeda@tokyo.ndu.ac.jp
authors.forename: M
authors.initials: M
authors.lastname: Takeda
authors.forename: T
authors.initials: T
authors.lastname: Tanimoto
authors.forename: M
authors.initials: M
authors.lastname: Takahashi
authors.forename: J
authors.initials: J
authors.lastname: Kadoi
authors.forename: M
authors.initials: M
authors.lastname: Nasu
authors.forename: S
authors.initials: S
authors.lastname: Matsumoto
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism*; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D002574:Cervical Vertebrae; D003392:Cranial Sinuses / Q000294:innervation* / Q000502:physiology; D003782:Dental Pulp / Q000294:innervation* / Q000502:physiology; D004347:Drug Interactions / Q000502:physiology; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D018341:Receptors, Adrenergic, alpha-2; D018698:Glutamic Acid