ABSTRACT
Recent studies have shown that the incidence of chronic primary pain including temporomandibular disorders (TMD) and fibromyalgia syndrome (FMS) often exhibit comorbidities. We recently reported that central sensitization and descending facilitation system contributed to the development of somatic pain hypersensitivity induced by orofacial inflammation combined with stress. The purpose of this study was to explore whether TMD caused by unilateral anterior crossbite (UAC) can induce somatic pain hypersensitivity, and whether the cholecystokinin (CCK) receptor-mediated descending facilitation system promotes hypersensitivity through neuron-glia cell signaling cascade. UAC evoked thermal and mechanical pain hypersensitivity of the hind paws from day 5 to 70 that peaked at week 4 post UAC. The expression levels of CCK1 receptors, interleukin-18 (IL-18) and IL-18 receptors (IL-18R) were significantly up-regulated in the L4 to L5 spinal dorsal horn at 4 weeks post UAC. Intrathecal injection of CCK1 and IL-18 receptor antagonists blocked somatic pain hypersensitivity. IL-18 mainly co-localized with microglia, while IL-18R mainly co-localized with astrocytes and to a lesser extent with neurons. These findings indicate that the signaling transduction between neurons and glia at the spinal cord level contributes to the descending pain facilitation through CCK1 receptors during the development of the comorbidity of TMD and FMS. PERSPECTIVE: CCK1 receptor-dependent descending facilitation may mediate central mechanisms underlying the development of widespread somatic pain via a reciprocal neuron-glial signaling cascade, providing novel therapeutic targets for the clinical treatment of TMD and FMS comorbidities.
Subject(s)
Chronic Pain , Malocclusion , Nociceptive Pain , Receptor, Cholecystokinin B , Animals , Cholecystokinin/metabolism , Chronic Pain/metabolism , Hyperalgesia/metabolism , Interleukin-18/metabolism , Malocclusion/metabolism , Neuroglia/physiology , Neurons , Nociceptive Pain/metabolism , Rats , Rats, Sprague-Dawley , Receptor, Cholecystokinin B/metabolism , Receptors, Interleukin-18/metabolism , Signal Transduction/physiology , Spinal Cord , Spinal Cord Dorsal Horn/metabolismABSTRACT
PURPOSE: To investigate the effect of low-magnitude high frequency vibration (LMHFV) on proliferation, migration ability and osteogenic differentiation of human periodontal ligament stem cells(hPDLSCs). METHODS: hPDLSCs were isolated from premolar and randomized into vibration culture group (magnitudeï¼0.3 g; frequencyï¼40 Hz; timeï¼15 min/24 h) and static culture group. CCK-8 was used to identity the proliferation of hPDLSCs. Wound-healing assay was used to evaluate migration ability of hPDLSCs. The osteogenesis gene expression was analyzed by RT-PCR, and the osteogenesis protein expression was analyzed by Western blot. The osteogenesis differentiation capability was evaluated by alizarin red staining. The data were analyzed using SPSS 21.0 software package. RESULTS: After LMHFV, the proliferation and migration ability of hPDLSCs were increased. The expression level of RUNX2, ALP, Col-1, and OCN was significantly augmented under LMHFV. Alizarin red staining and Western blot proved the same trend. CONCLUSIONSï¼The results demonstrate that LMHFV can promote hPDLSCs proliferation, migration ability and osteogenic differentiation.
