Abstract
Chronic neuropathic pain constitutes a serious public health problem, but the disease mechanisms are only partially understood. The involvement of different brain regions like the medial prefrontal cortex has already been established, but the comparison of the role of different subregions and layers is still inconclusive. In the current study, we performed patch-clamp recordings followed by anatomical reconstruction of pyramidal cells from different layers of the prelimbic and infralimbic subregions of the medial prefrontal cortex in neuropathic (spared nerve injury, SNI) and control mice. We found that in the prelimbic cortex, layer 2/3 pyramidal cells from SNI mice exhibited increased excitability compared to sham controls, whereas prelimbic layer 5 pyramidal neurons showed reduced excitability. Pyramidal cells in both layer 2/3 and layer 5 of the infralimbic subregion did not change their excitability, but layer 2/3 pyramidal cells displayed increased dendritic length and branching. Our findings support the view that chronic pain is associated with subregion- and layer-specific changes in the medial prefrontal cortex. They therefore provide new insights into the mechanisms underlying the chronification of pain.
Highlights
Chronic neuropathic pain constitutes a serious public health problem that affects a large number of individuals worldwide[1,2,3,4]
In order to investigate whether the spared nerve injury (SNI) mouse model induces layer specific and subregion specific electrophysiological and morphological changes in pyramidal cells of the medial prefrontal cortex, we performed whole-cell patch clamp recordings and subsequent morphological analyses in a subset of recorded neurons 7 days after surgery
We used a combined electrophysiological and morphological approach to assess alterations of medial prefrontal cortex (mPFC) pyramidal neurons induced by neuropathic nerve injury with a special focus on subregional and laminar specificity
Summary
Chronic neuropathic pain constitutes a serious public health problem that affects a large number of individuals worldwide[1,2,3,4]. The medial prefrontal cortex (mPFC), which is primarily known for its prominent role in attention and goal-directed behavior[9], provides top-down regulation of sensory and affective processes[10], including inhibition of both sensory and affective nociceptive signals by descending projections to various brain and spinal cord regions[11,12,13] In both human subjects and rodent models, the mPFC undergoes structural as well as functional changes in chronic pain states[14,15,16,17,18,19,20,21], which are reflected by cognitive deficits and decreased attention (for review see[22]). The current study is the first to systematically dissect the effects of persistent nociceptive activity from the spared nerve injury model of neuropathic pain on pyramidal neurons of layers 2/3 and layer 5 in the PrL and IL mPFC subregions, providing evidence for subregion- and layer-specific alterations of electrophysiological properties and dendritic complexity
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