Loss of inhibitory tone on spinal cord dorsal horn spontaneously and nonspontaneously active neurons in a mouse model of neuropathic pain
PAIN. 2016-02-26; 157(7): 1432-1442
DOI: 10.1097/j.pain.0000000000000538
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Medrano MC(1), Dhanasobhon D(1)(2), Yalcin I(1), Schlichter R(1)(2), Cordero-Erausquin M(1)(3).
Author information:
(1)Institut des Neurosciences Cellulaires et Intégratives, CNRS UPR3212, Strasbourg, France.
(2)Université de Strasbourg, Strasbourg, France.
(3)University of Strasbourg Institute for Advanced Study (USIAS), Strasbourg, France.
Plasticity of inhibitory transmission in the spinal dorsal horn (SDH) is believed
to be a key mechanism responsible for pain hypersensitivity in neuropathic pain
syndromes. We evaluated this plasticity by recording responses to mechanical
stimuli in silent neurons (nonspontaneously active [NSA]) and neurons showing
ongoing activity (spontaneously active [SA]) in the SDH of control and
nerve-injured mice (cuff model). The SA and NSA neurons represented 59% and 41%
of recorded neurons, respectively, and were predominantly wide dynamic range
(WDR) in naive mice. Nerve-injured mice displayed a marked decrease in the
mechanical threshold of the injured paw. After nerve injury, the proportion of SA
neurons was increased to 78%, which suggests that some NSA neurons became SA. In
addition, the response to touch (but not pinch) was dramatically increased in SA
neurons, and high-threshold (nociceptive specific) neurons were no longer
observed. Pharmacological blockade of spinal inhibition with a mixture of GABAA
and glycine receptor antagonists significantly increased responses to innocuous
mechanical stimuli in SA and NSA neurons from sham animals, but had no effect in
sciatic nerve-injured animals, revealing a dramatic loss of spinal inhibitory
tone in this situation. Moreover, in nerve-injured mice, local spinal
administration of acetazolamide, a carbonic anhydrase inhibitor, restored
responses to touch similar to those observed in naive or sham mice. These results
suggest that a shift in the reversal potential for anions is an important
component of the abnormal mechanical responses and of the loss of inhibitory tone
recorded in a model of nerve injury-induced neuropathic pain.