Properties of spinal lamina III GABAergic neurons in naive and in neuropathic mice

Background: Nerve injury leads to A beta-fibre-mediated mechanical allodynia that is in part due to an impaired GABAergic inhibition in the spinal cord dorsal horn. The properties and function of GABAergic neurons in spinal cord lamina III, an area where low-threshold mechanosensitive A beta-fibres terminate are, however, largely unknown. Methods: We used transgenic mice, which express enhanced green fluorescent protein (EGFP) under control of the promoter GAD67. The morphology and neurochemical characteristics of GABAergic, EGFP-expressing neurons were characterized. We assessed active and passive membrane properties of spinal lamina III GABAergic neurons in naive animals and animals with a chronic constriction injury (CCI) of the sciatic nerve. Results: EGFP-expressing neurons in lamina III were predominantly islet cells (47%), whereas non-EGFP-expressing neurons were largely inverted stalked cells (40%). EGFP-expressing neurons accounted for about 25% of GABAergic neurons in lamina III. Forty-four percent co-expressed glycine, 10% neuronal nitric oxide synthase and 3% co-expressed parvalbumin. We found costaining with protein kinase C beta II in 42% of EGFP-expressing neurons but no expression of protein kinase C gamma. Membrane properties and excitability of EGFP-and non-EGFP-expressing neurons from naive and neuropathic animals were indistinguishable. The most frequent firing pattern was tonic firing (naive: 35%, neuropathic: 37%) followed by gap firing (naive: 33%, neuropathic: 25%). Delayed, initial burst and single-spike firing patterns made up the remainder in both groups. Conclusion: A change in membrane excitability or discharge pattern of this group of lamina III GABAergic neurons is unlikely the cause for mechanical allodynia in animals with CCI.