Effects of GABAA receptors in nucleus cuneiformis on the cannabinoid antinociception using the formalin test.

Rationale: Nucleus cuneiformis (NC), a reticular nucleus of the midbrain, is a part of the descending pain modulatory system and therefore has an important role in pain perception.
Objectives: Considering the abundance of GABA _A and cannabinoid receptors in the NC and also the bidirectional roles for GABA in controlling nociception, the present study examined the effects of bilateral intra-NC microinjection of different doses of the GABA _A receptor agonist, muscimol, and the GABA _A receptor antagonist, bicuculline, on pain modulation using formalin test. We also assessed interaction between canabinergic and GABAergic systems in the NC during this test.
Methods: Rats were exposed to intra-NC microinjection of bicuculline (50,100, and 200 ng/side) or muscimol (60, 120, and 240 ng/side) and then subjected to the formalin test. In another set of experiments, the effects of muscimol (60 ng/side) or bicuculline (50 ng/side) administration 5 min before a cannabinoid receptor agonist WIN 55,212-2 (5, 10, and 20 μg/side) microinjection into NC on the formalin test were evaluated.
Results: Microinjection of bicuculline and muscimol into the NC decreased and increased pain responses, respectively, in a dose-dependent manner during both phases of the test. Microinjection of WIN 55,212-2 into the NC significantly reduced pain responses in a dose-dependent manner. Microinjection of bicuculline or muscimol in combination with WIN 55,212-2 into the NC respectively potentiated and attenuated WIN 55,212-2-induced antinociception in the formalin test.
Conclusions: This study shows that GABA in the NC is involved in pain modulation and suggests the existence of a GABA _A -mediated inhibitory system in the NC on pain control. Furthermore, it seems that the antinociceptive effect of WIN 55,212-2 in the formalin test is mediated partly by the activity of local GABA _A receptors in the NC.