Human Informatics and Interaction Research Institute, National Institute of Advanced Industrial Science and Technology, Ibaraki, Japan.
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba-City, Japan.
Eur J Pain. 2022 Sep;26(8):1723-1731. doi: 10.1002/ejp.1996. Epub 2022 Jul 1.
We previously established a macaque model of central post-stroke pain (CPSP) and confirmed the involvement of increased activity of the posterior insular cortex (PIC) and secondary somatosensory cortex (SII) to somatosensory stimuli in mechanical allodynia by a combination of imaging techniques with local pharmacological inactivation. However, it is unclear whether the same intervention would be effective for thermal hyperalgesia. Therefore, using the macaque model, we examined behavioural responses to thermal stimuli following pharmacological inactivation of the PIC/SII.
Two CPSP model macaques were established based on collagenase-induced unilateral hemorrhagic lesions in the ventral posterolateral nucleus of the thalamus. To evaluate pain perception, withdrawal latencies to thermal stimuli of 37, 45, 50, 52, and 55 °C to hands were measured. Several weeks after the lesion induction, pharmacological inactivation of the PIC/SII by microinjection of muscimol was performed. The effect of inactivation on withdrawal latency was assessed by comparison with withdrawal latency after vehicle injection.
Several weeks after induction of the thalamic lesions, both macaques demonstrated a reduction in withdrawal latencies to thermal stimulation (<50 °C) on the contralesional hand, indicating the occurrence of thermal hyperalgesia. When the PIC/SII were inactivated by muscimol, the withdrawal latencies to thermal stimuli of 50 and 52 °C were significantly increased compared to those after vehicle injection.
Our data emphasize that increased activity in the PIC/SII after appearance of thalamic lesions can contribute to abnormal pain of multiple modalities, and the modulation of PIC/SII activity may be a therapeutic approach for thermal hyperalgesia.
CPSP is caused by stroke lesions in the sensory system and characterized by mechanical allodynia or thermal hyperalgesia. Inactivation of the PIC/SII has an analgesic effect on mechanical allodynia; however, it is not clear whether the same intervention could reduce thermal hyperalgesia. Here, using the macaque model, we demonstrated that inactivation of these cortices reduces hypersensitivity to thermal stimuli. This result emphasizes that increased PIC/SII activity can contribute to abnormal pain of multiple modalities.
我们之前建立了猕猴中枢性卒中后疼痛（CPSP）模型，并通过影像学技术与局部药理学失活相结合，证实了后岛叶皮质（PIC）和次级体感皮质（SII）对体感刺激的活性增加与机械性痛觉过敏有关。然而，对于热痛觉过敏，同样的干预是否有效尚不清楚。因此，我们使用猕猴模型，在 PIC/SII 的药理学失活后，研究了对热刺激的行为反应。
根据胶原酶诱导的丘脑腹后外侧核单侧出血性损伤，建立了 2 只 CPSP 模型猕猴。为了评估疼痛感知，测量手对 37、45、50、52 和 55°C 热刺激的退缩潜伏期。在损伤诱导后数周，通过微注射 muscimol 对 PIC/SII 进行药理学失活。通过与载体注射后退缩潜伏期的比较，评估失活对退缩潜伏期的影响。
在丘脑损伤诱导后数周，两只猕猴对热刺激（<50°C）的对侧手退缩潜伏期均降低，表明出现了热痛觉过敏。当 PIC/SII 被 muscimol 失活时，与载体注射后相比，50 和 52°C 的热刺激退缩潜伏期显著增加。
我们的数据强调，丘脑损伤后 PIC/SII 活性的增加可能导致多种感觉模式的异常疼痛，调节 PIC/SII 活性可能是治疗热痛觉过敏的一种方法。
CPSP 是由感觉系统的中风损伤引起的，其特征是机械性痛觉过敏或热痛觉过敏。PIC/SII 的失活对机械性痛觉过敏有镇痛作用；然而，尚不清楚相同的干预是否可以减轻热痛觉过敏。在这里，我们使用猕猴模型证明了这些皮质的失活可以降低对热刺激的敏感性。这一结果强调了 PIC/SII 活性的增加可能导致多种感觉模式的异常疼痛。
