Physiological properties of spinal lamina II GABAergic neurons in mice following peripheral nerve injury

Abstract

Aberrant GABAergic inhibition in spinal dorsal horn may underlie some forms of neuropathic pain. Potential, but yet unexplored, mechanisms include reduced excitability, abnormal discharge patterns or altered synaptic input of spinal GABAergic neurons. To test these hypotheses, we quantitatively compared active and passive membrane properties, firing patterns in response to depolarizing current steps and synaptic input of GABAergic neurons in spinal dorsal horn lamina II of neuropathic and of control animals. Transgenic mice were used which expressed enhanced green fluorescent protein (EGFP) controlled by the GAD67 promoter, thereby labelling one-third of all spinal GABAergic neurons. In all neuropathic mice included in this study, chronic constriction injury of one sciatic nerve led to tactile allodynia and thermal hyperalgesia. Control mice were sham-operated. Membrane excitability of GABAergic neurons from neuropathic or sham-treated animals was indistinguishable. The most frequent firing patterns observed in neuropathic and sham-operated animals were the initial burst (neuropathic: 46%, sham-treated: 42%), the gap (neuropathic: 31%, sham-treated: 29%) and the tonic firing pattern (neuropathic: 16%, sham-treated: 24%). The synaptic input from dorsal root afferents was similar in neuropathic and in control animals. Thus, a reduced membrane excitability, altered firing patterns or changes in synaptic input of this group of GABAergic neurons in lamina II of the spinal cord dorsal horn are unlikely causes for neuropathic pain.

Modification of classical neurochemical markers in identified primary afferent neurons with Aβ‐, Aδ‐, and C‐fibers after chronic constriction injury in mice

“…As described previously for the same strain (Schoffnegger et al, 2006), mice developed significant mechanical allodynia and thermal hyperalgesia in the ipsilateral hindpaw on the day following loose ligation of the sciatic The Journal of Comparative Neurology. DOI 10.1002/cne nerve, and this behavior remained stable throughout the examination period (mechanical thresholds preoperatively: 0.93 Ϯ 0.12 g, on day 1 after ligation: 0.09 Ϯ 0.03 g, on day 9 after ligation: 0.01 Ϯ 0.00 g; thermal withdrawal latencies at the same time points: 6.1 Ϯ 0.2 seconds, 1.8 Ϯ 0.1 seconds, and 1.3 Ϯ 0.1 seconds; n ϭ 7, P Ͻ 0.01, two-way ANOVA followed by Tukey test).…”

Effects of Sciatic Nerve Axotomy on Excitatory Synaptic Transmission in Rat Substantia Gelatinosa

“…Additional evidence to support the latter idea comes from ultrastructural studies that show that CCI promotes transient loss of the excitatory synaptic terminals of nonpeptidergic nociceptive fibers in substantia gelatinosa (Bailey and Ribeiro-da-Silva 2006). This is relevant because these fibers form the synaptic terminals of type 1 synaptic glomeruli (Ribeiro-da-Silva and Coimbra 1982) that associate with GABAergic neurons (Todd 1996), many of which display a tonic firing pattern (Labrakakis et al 2009;Lu and Perl 2003;Schoffnegger et al 2006).…”

“…First, their intracellular stimulation during paired recording experiments produces excitatory events in postsynaptic neurons (Lu and Perl 2005). Second, studies using a transgenic mouse that coexpresses enhanced green fluorescent protein under the control of the GAD-67 promotor have associated the GABA phenotype with initial burst (phasic), gap (irregular), or tonic neurons and not with delay neurons (Schoffnegger et al 2006).…”

Neuropathic Pain: A Review of Interneuronal Disinhibition

“…Based on these findings, the firing pattern of inhibitory interneurons could be altered in NP. However, Schoffnegger et al (33) found no supporting evidence for this hypothesis.…”

“…Schoffnegger et al (33) conducted a study regarding the physiological properties of lamina II GABAergic neurons after nerve injury. They used GFP-expressing mice under the control of GAD67 promoter.…”