Sikandar Shafaq, West Steven J, McMahon Stephen B, Bennett David L, Dickenson Anthony H
Wolfson Institute of Biomedical Research, University College London, London, United Kingdom
Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital, Oxford, United Kingdom.
Physiol Rep. 2017 Jul;5(14). doi: 10.14814/phy2.13323.
Sensory processing of deep somatic tissue constitutes an important component of the nociceptive system, yet associated central processing pathways remain poorly understood. Here, we provide a novel electrophysiological characterization and immunohistochemical analysis of neural activation in the lateral spinal nucleus (LSN). These neurons show evoked activity to deep, but not cutaneous, stimulation. The evoked responses of neurons in the LSN can be sensitized to somatosensory stimulation following intramuscular hypertonic saline, an acute model of muscle pain, suggesting this is an important spinal relay site for the processing of deep tissue nociceptive inputs. Neurons of the thalamic ventrobasal complex (VBC) mediate both cutaneous and deep tissue sensory processing, but in contrast to the lateral spinal nucleus our electrophysiological studies do not suggest the existence of a subgroup of cells that selectively process deep tissue inputs. The sensitization of polymodal and thermospecific VBC neurons to mechanical somatosensory stimulation following acute muscle stimulation with hypertonic saline suggests differential roles of thalamic subpopulations in mediating cutaneous and deep tissue nociception in pathological states. Overall, our studies at both the spinal (lateral spinal nucleus) and supraspinal (thalamic ventrobasal complex) levels suggest a convergence of cutaneous and deep somatosensory inputs onto spinothalamic pathways, which are unmasked by activation of muscle nociceptive afferents to produce consequent phenotypic alterations in spinal and thalamic neural coding of somatosensory stimulation. A better understanding of the sensory pathways involved in deep tissue nociception, as well as the degree of labeled line and convergent pathways for cutaneous and deep somatosensory inputs, is fundamental to developing targeted analgesic therapies for deep pain syndromes.
深部躯体组织的感觉处理是伤害感受系统的重要组成部分,但相关的中枢处理通路仍知之甚少。在此,我们对脊髓外侧核(LSN)中的神经激活进行了新颖的电生理特征描述和免疫组织化学分析。这些神经元对深部刺激而非皮肤刺激表现出诱发活动。在肌肉疼痛的急性模型——肌内注射高渗盐水后,LSN中神经元的诱发反应可对体感刺激敏感化,这表明该区域是处理深部组织伤害性输入的重要脊髓中继位点。丘脑腹侧基底复合体(VBC)的神经元介导皮肤和深部组织的感觉处理,但与脊髓外侧核不同,我们的电生理研究未表明存在选择性处理深部组织输入的细胞亚群。在用高渗盐水急性刺激肌肉后,多模式和热特异性VBC神经元对机械体感刺激的敏感化表明,丘脑亚群在介导病理状态下皮肤和深部组织伤害感受中具有不同作用。总体而言,我们在脊髓(脊髓外侧核)和脊髓上(丘脑腹侧基底复合体)水平的研究表明,皮肤和深部体感输入汇聚到脊髓丘脑通路,肌肉伤害性传入纤维的激活可揭示这些通路,从而在脊髓和丘脑对体感刺激的神经编码中产生相应的表型改变。更好地理解参与深部组织伤害感受的感觉通路,以及皮肤和深部体感输入的标记线和汇聚通路的程度,对于开发针对深部疼痛综合征的靶向镇痛疗法至关重要。