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. 2017 Aug 10:655:82-89.
doi: 10.1016/j.neulet.2017.07.006. Epub 2017 Jul 6.

Ablation of IB4 non-peptidergic afferents in the rat facet joint prevents injury-induced pain and thalamic hyperexcitability via supraspinal glutamate transporters

Christine L Weisshaar  1 , Jeffrey V Kras  1 , Parul S Pall  1 , Sonia Kartha  1 , Beth A Winkelstein  2
Affiliations

Ablation of IB4 non-peptidergic afferents in the rat facet joint prevents injury-induced pain and thalamic hyperexcitability via supraspinal glutamate transporters

Christine L Weisshaar et al. Neurosci Lett. .

Abstract

The facet joint is a common source of neck pain, particularly after excessive stretch of its capsular ligament. Peptidergic afferents have been shown to have an important role in the development and maintenance of mechanical hyperalgesia, dysregulated nociceptive signaling, and spinal hyperexcitability that develop after mechanical injury to the facet joint. However, the role of non-peptidergic isolectin-B4 (IB4) cells in mediating joint pain is unknown. Isolectin-B4 saporin (IB4-SAP) was injected into the facet joint to ablate non-peptidergic cells, and the facet joint later underwent a ligament stretch known to induce pain. Behavioral sensitivity, thalamic glutamate transporter expression, and thalamic hyperexcitability were evaluated up to and at day 7. Administering IB4-SAP prior to a painful injury prevented the development of mechanical hyperalgesia that is typically present. Intra-articular IB4-SAP also prevented the upregulation of the glutamate transporters GLT-1 and EAAC1 in the ventral posterolateral nucleus of the thalamus and reduced thalamic neuronal hyperexcitability at day 7. These findings suggest that a painful facet injury induces changes extending to supraspinal structures and that IB4-positive afferents in the facet joint may be critical for the development and maintenance of sensitization in the thalamus after a painful facet joint injury.

Keywords: Brain; Facet joint; Glutamate transporter; Neuronal hyperexcitability; Pain.

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Figures

Fig. 1
Fig. 1
Forepaw mechanical hyperalgesia in response to von Frey filament stimulation. Injury with vehicle injection (vehicle injury) exhibits significantly reduced response thresholds starting at day 1 and persisting until day 7 compared to both IB4-SAP injury and IB4-SAP sham (*p
Fig. 2
Fig. 2
Neuronal hyperexcitability in the VPL of the thalamus at day 7. (A) Facet joint injury significantly increases the number of spikes evoked in the VPL in response to forepaw stimulation by 1.4, 4, 10, and 26g von Frey filaments, compared to all other groups (*p<0.017). (B) Neuronal hyperexcitability also increases after facet joint injury compared to all other groups (*p<0.0097) in response to both the brush and pinch stimuli. (C) Representative extracellular recordings during stimulation for each group; the scale bar represents 5 seconds. Data in (A) and (B) are reported as the mean±standard error of the mean.
Fig. 3
Fig. 3
Representative images and quantification of GLT-1 and EAAC1 expression in the VPL of the thalamus at day 7. (A) Representative images of GLT-1 and EAAC1 expression in the VPL. The scale bar is 100μm and applies to all panels. (B) Thalamic expression of GLT-1 is significantly increased (*p<0.0198) after injury compared to all of the other groups: sham, IB4-SAP injury, and IB4-SAP sham and normal tissue. (C) Similarly, labeling of EAAC1 is elevated (#p<0.0006) following vehicle injury compared to all other groups. Data in (B) and (C) are reported as the mean±standard deviation.
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