Late-onset thermal hypersensitivity after focal ischemic thalamic infarcts as a model for central post-stroke pain in rats

Abstract

Central post-stroke pain (CPSP) is a neuropathic pain syndrome that often develops in a delayed manner after thalamic stroke. Here, we describe a new model of CPSP by stereotaxic thalamic injection of endothelin-1. Stroke rats (n = 12), but not saline-injected controls (n = 12), developed a progressive, contralateral cutaneous thermal hyperalgesia over 4 weeks, without motor deficits. Lesions were highly focal and mainly affected the ventral posterior thalamic complex. Tchis model reproduces the infarct location and delayed hypersensitivity typical of CPSP, and may be useful to investigate its pathophysiology and test therapies targeting recovery and pain after thalamic stroke.

Figure 1

Late-onset thermal hypersensitivity after thalamic stroke. (A) Thermal hypersensitivity detected with Hargreaves's test. (B) Mechanical sensitivity assessed with von Frey's test. (C–E) There was no motor or exploratory deficit after thalamic stroke. *P=0.004 (F=10.04), versus contralateral; two-way analysis of variance for repeated measures followed by Bonferroni post-hoc test. ^#P=0.018, versus control; Mann–Whitney U-test. N=12/group. Error bars are represented as s.d.

Figure 2

Thalamic infarction 1 month after stroke. (A) LFB-CV and (B) H&E-stained sections from a representative animal showing thalamic infarction (dotted lines) 1 month after endothelin-1 injection. (C). Hypercellularity detected at the level of the infarct site (asterisk). (D–F) Normal histology after vehicle injection. (G) Probabilistic map of thalamic infarct location (adapted from ref. 14). Each superimposed gray-shaded outline represents the lesion in one rat. The darkest area corresponds to the area most often affected by the infarct. Distance from Bregma (mm) is reported on the upper right corner of each image. (H) Infarct distribution; scatter plots represent individual measurements. (I) Total infarct volume in individual brain regions represented by filled bars; whole bars (empty+filled) represent the total volume (healthy+injured) of each brain region. Scale bars, 2 mm (A, B, D, and E), 0.3 mm (C and F). N=12/group. Error bars are represented as s.d. CV, cresyl violet; H&E, hematoxylin and eosin; IC, internal capsule; LFB, luxol fast blue; PO, posterior; RT, reticulus thalamic; VL, ventrolateral; VM, ventromedial; VPL, ventral posterolateral; VPM, ventral posteromedial; ZI, zona incerta.