A Role of Glutamate and GABA Receptors in the Generation of Formalin-induced Impulse Firing of Spinal Dorsal Horn Neurons in the Rat

Background: A peripheral subcutaneous injection of formalin produces biphasic impulse firing of the spinal nociceptive neurons. The roles of excitatory glutamatergic and inhibitory GABAergic receptors were investigated in the formalin-induced impulse generation of rat spinal neurons. Methods: The neuronal activity was recorded, extracellularly, from the spinal nociceptive neurons of rats spinalized at L1. Formalin (2.5%, 50,) was injected into the plantar spot near the receptive field of the recorded neuron. Agonists and antagonists, for glutamatergic and GABAergic receptors, were applied topically onto the surface of the spinal cord near the recording electrode. Results: The plantar injection of formalin evoked typical biphasic firing of the spinal neurons. When applied before the formalin injection, AMPA receptor antagonists blocked the first firing, while the receptor antagonist, NMDA and mGlu, blocked the second firing. When applied before the formalin injection, or during the interphase, receptor antagonists, GABA-A and GABA-B, facilitated the second firing to occur. When applied during the second firing, the receptor antagonists, NMDA, AMPA and mGlu, all blocked the second firing, while the receptor antagonists, GABA-A and GABA-B, had no effect. Conclusions: The results indicated that: 1) the formalin-produced first firing is mediated by AMPA receptor activation, 2) the first firing is followed by GABAergic inhibition, which contributes to the formation of the interphase, via activation of GABA-A and GABA-B receptors, and 3) the induction of the second firing is mediated by the diminution of GABAergic inhibition, as well as the activation of the NMDA and mGlu receptors, while being mediated in its maintenance by the activation of NMDA, AMPA and mGlu receptors.