Increase in GABAergic Cells and GABA Levels in the Spinal Cord in Unilateral Inflammation of the Hindlimb in the Rat.

The effects of chronic peripheral inflammation on spinal cord gamma-aminobutyric acid (GABA) were examined in the rat. Following the injection of complete Freund's adjuvant in the left hindlimb footpad an increased number of immunoreactive cells occurred in ipsilateral laminae I - III of the dorsal horn from L3 to L5. GABA-immunoreactive cells were more numerous than contralaterally 1 week after the onset of the inflammation, reached maximal numbers after 3 - 4 weeks, and declined thereafter. Differences from control sides were statistically significant except at week 6. GABA levels in homogenates of the ipsilateral lumbar enlargement were increased significantly at 4 weeks. Since increases in GABA occurred in the spinal cord zone of projection of the nerves supplying the inflamed foot, the central response is surmised to result from the increased nociceptive input arriving from the periphery. However, the transmission from primary axons to GABA interneurons is not likely to be monosynaptic since profiles containing glutamate decarboxylase or GABA immunoreactivity are known to be predominantly presynaptic, and rarely postsynaptic, to primary afferent endings in electron micrographs in the rat. The findings support the function attributed to spinal GABA in modulating nociceptive input at segmental level.