Expression of GAD mRNA in spinal cord neurons of normal and monoarthritic rats

Abstract

This study was carried out to investigate whether the increase of GABA levels in spinal cord dorsal horn in response to chronic inflammatory lesions results from an enhanced expression of the gene that governs the production of glutamate decarboxylase (GAD), the enzyme responsible for GABA synthesis. In situ hybridization was used to visualize neurons expressing GAD mRNA within the spinal cord, in both intact rats and in animals bearing chronic monoarthritis induced by intraarticular injection of complete Freund's adjuvant. In control normal animals, neuronal labeling by an antisense oligonucleotide probe occurred throughout the spinal gray matter, except in the motoneuronal pool of Rexed's lamina IX. In treated animals 4 days after the induction of monoarthritis, a significant increase in the number of labeled cells occurred in the superficial laminae (25.3%) and the neck (17.2%) of the ipsilateral dorsal horn at segments L 4-L 5 which contain the projection domain of the ankle joint. At 2 weeks, values were, respectively, 20.2% and 13.9% over contralateral values, and an increase of 12.4% was found in the ventral horn. At 3 weeks, the ipsilateral increase of labeled cells was restricted to the superficial dorsal horn (15.2%). These findings emphasize the role played by the spinal GABAergic system in the modulation of chronic nociceptive input. It is suggested that the response of the spinal GABAergic system depends on the activation of GAD gene transcription in spinal neurons.