Functional Role of Supra Spinal and Spinal GABA Receptor Subtypes on Formalin-induced Nociceptive Pain

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  • フォルマリン誘発疼痛反応における脳ならびに腰髄内GABA受容体サブタイプの機能的役割
  • フォルマリン ユウハツ トウツウ ハンノウ ニ オケル ノウ ナラビニ ヨウズイナイ GABA ジュヨウタイ サブタイプ ノ キノウテキ ヤクワリ

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Abstract

Of the neuronal GABA receptors of the spinal cord and the supra spinal cord, two subtypes of GABA receptors play important roles in pain regulation. In this experiment, we compared the effects of intrathecal and lateral-ventricular injections of either GABAa or GABAb receptor ligand on secondary nociception induced by formalin using male Wistar rats (300-350g). As specific ligands for each GABA receptor subtype, muscimol (a GABAa agonist), baclofen (a GABAb agonist) and phaclofen (an inhibitor of GABAb receptor) were used. All agents were administered intrathecally (i.t.) or intraventricularly (i.c.v) 10min prior to formalin injection. Flinching was quantified in five minute intervals for 60min. Between zero and 15min, flinching response was defined as the first phase, and the second phase of this response was between 16 and 60min of the observation period. An i.t. injection of muscimol (15nmol) diminished both phases of formalin-induced flinching response with a muscle relaxation, although a low dose (1.5nmol) of muscimol suppressed the second phase of this response with a weak muscle relaxation. Both low and high doses of muscimol i.c.v. treatments did not effect both phases of response. An i.t. injection of baclofen (1.5nmol) significantly inhibited the second phase responses, although a high dose of baclofen did inhibit both phases of flinching response with muscle relaxation. In contrast, an i.c.v. injection of baclofen significantly enhanced the nociceptive response in a dose-dependent manner with clonic convulsions. However this enhancement of nociceptive response was significantly inhibited by phaclofen, although the convulsion induced by a high dose of baclofen was not influenced. In conclusion, the GABAa receptor in the central nervous system may not relate to the pathway of the formalin-induced nociception, but the spinal GABAb receptor appear to influence strongly this nociceptive response. Furthermore the supraspinal GABAb receptor may locate on the presynaptic neurons and stimulate the excitatory transmissions.

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