Hoheisel Ulrich, Treede Rolf-Detlef, Mense Siegfried, Taguchi Toru
Department of Neurophysiology, Mannheim Center for Translational Neurosciences, Ruprecht- Karls-University Heidelberg, 68167, Mannheim, Germany.
Department of Psychiatry and Psychotherapy, Central Institute for Mental Health, Ruprecht- Karls-University Heidelberg, 68167, Mannheim, Germany.
Sci Rep. 2025 Jan 20;15(1):2552. doi: 10.1038/s41598-025-86832-z.
Since clinical features of chronic muscle pain originating from the low back and limbs are different (higher prevalence and broader/duller sensation of low back muscle pain than limb muscle pain), spinal and/or supraspinal projection of nociceptive information could differ between the two muscles. We tested this hypothesis using c-Fos immunohistochemistry combined with retrograde-labeling of dorsal horn (DH) neurons projecting to ventrolateral periaqueductal grey (vlPAG) or ventral posterolateral nucleus of the thalamus (VPL) by fluorogold (FG) injections into the vlPAG or VPL. C-Fos expression in the DH was induced by injecting 5% formalin into the multifidus (MF, low back) or gastrocnemius-soleus (GS, limb) muscle. A double-labeled DH neuron showing both c-Fos-immunoreactive nucleus and retrogradely transported FG in the cytoplasm was considered as a nociceptive projection neuron. Consistent with DH somatotopy for proximal vs. distal cutaneous inputs, DH neurons with MF input were located in the most lateral area of laminae I - II (segments Th12 - L5), while those with GS input were located in the middle area of laminae I - II (L3 - L5). DH neurons projecting to the vlPAG were located in superficial DH, while those projecting to VPL were located in deep DH. Supraspinal projection derived from more spinal segments for MF input than for GS input. These data suggest that nociceptive input from low back muscles is integrated more in craniocaudal direction than for limb muscles, and that these signals are then forwarded to both PAG and thalamus and contribute to the different nature of muscle pain arising from the low back and limbs.
由于源自腰背部和四肢的慢性肌肉疼痛的临床特征有所不同(腰背部肌肉疼痛的患病率更高,且感觉比四肢肌肉疼痛更广泛/更钝),这两块肌肉的伤害性信息的脊髓和/或脊髓上投射可能存在差异。我们通过将荧光金(FG)注射到腹外侧导水管周围灰质(vlPAG)或丘脑腹后外侧核(VPL),结合c-Fos免疫组织化学和逆行标记投射到vlPAG或VPL的背角(DH)神经元,来验证这一假设。通过向多裂肌(MF,腰背部)或腓肠肌-比目鱼肌(GS,四肢)注射5%福尔马林来诱导DH中的c-Fos表达。一个双标记的DH神经元,其细胞核显示c-Fos免疫反应性且细胞质中有逆行运输的FG,被视为伤害性投射神经元。与近端与远端皮肤输入的DH躯体定位一致,接受MF输入的DH神经元位于I-II层的最外侧区域(胸12-腰5节段),而接受GS输入的DH神经元位于I-II层的中间区域(腰3-腰5)。投射到vlPAG的DH神经元位于浅层DH,而投射到VPL的DH神经元位于深层DH。与GS输入相比,来自更多脊髓节段的脊髓上投射源自MF输入。这些数据表明,来自腰背部肌肉的伤害性输入在头尾方向上比四肢肌肉的整合程度更高,并且这些信号随后被传递到PAG和丘脑,导致腰背部和四肢肌肉疼痛的性质不同。