ObjectiveAlthough nociceptive sensitisation is an important pathophysiological process in migraine and migraine chronification, its underlying mechanisms remain unclear. Toll-like receptor 4 (TLR4), a pattern-recognition molecule, has a critical role in both neuropathic pain and morphine tolerance. The present study examined whether elements of the TLR4 pathway contribute to hyperalgesia induced by dural inflammation in rats.MethodsA rat model of migraine was established by infusing a dural inflammatory soup. A group pretreated with TAK-242 was used to inhibit the activation of TLR4. The protein levels of TLR4 and its downstream molecules in the trigeminal pathway were examined by Western blot and immunofluorescence. The expression of activated microglia and astrocytes was also analysed. Levels of interleukin-1 beta, tumour necrosis factor-alpha, and brain-derived neurotrophic factor were measured by enzyme-linked immunosorbent assay.ResultsAcute inflammatory soup infusion induced time-dependent facial mechanical hyperalgesia, which was blocked by TAK-242 pretreatment. The inflammatory soup stimulus increased the production of TLR4 downstream molecules and interleukin-1 beta. Higher levels of microglia activation and brain-derived neurotrophic factor release were observed following the administration of the inflammatory soup but were alleviated by TAK-242.ConclusionsThese data suggest that the TLR4 signalling pathway promotes hyperalgesia induced by acute inflammatory soup delivery by stimulating the production of proinflammatory cytokines and activating microglia.

Background Adrenoleukodystrophy is a rare neurogenetic disease, AMN is the most common adult phenotype, such patients in China have not gotten enough attention. This article aims to study the features of AMN in Chinese patients and expand the gene spectrum of Chinese X-linked adrenoleukodystrophy (X-ALD) patients. Methods We applied clinical analysis, radiology, plasma levels of very long chain fatty acids (VLCFA) and genetic analysis to test the 6 Chinese AMN patients. Results All 6 patients are men. Ages of neurological symptom onset are distributed between 21 and 38. Sexual dysfunction occurred in 5 of 6 patients. Three patients had positive family history. Five patients had Addison’s disease. Four patients were diagnosed as pure AMN, while the other two patients were with cerebral involvement. Four patients had abnormalities of nerve conduction studies. There were four patients with central conduction defects in somatosensory evoked potential tests. All 6 patients were found diffuse cord atrophy in spinal MRI. Brain MRI showed abnormal signals in 2 of the 6 tested patients, which indicated the clinical phenotypes. Plasma levels of VLCFA, as well as C24:0/C22:0 and C26:0/C22:0 ratios were elevated in 5 tested patients. Five different ABCD1 mutations were identified in 5 tested patients, one of which was a de novo mutation, and the other four have been reported previously. Conclusion This research described the clinical, neuroimaging, biochemical, and genetic sides of Chinese AMN patients. A de novo mutation in the ABCD1 gene sequence was identified. Emotional trauma may trigger or aggravate the development of cerebral demyelination in AMN patients. Regular evaluation of brain MRI is important for AMN patients, especially for ‘pure AMN’ patients. When encountering patients with ‘myeloneuropathy-only’, neurologists should not ignore the tests of VLCFA or/and the ABCD1 gene.

Background Adrenoleukodystrophy is a rare neurogenetic disease, AMN is the most common adult phenotype, such patients in China have not gotten enough attention.This article aims to study the features of AMN in Chinese patients and expand the gene spectrum of Chinese X-linked adrenoleukodystrophy (X-ALD) patients. Methods We applied clinical analysis, radiology, plasma levels of very long chain fatty acids (VLCFA) and genetic analysis to test the 6 Chinese AMN patients. Results All 6 patients are men. Ages of neurological symptom onset are distributed between 21 and 38. Sexual dysfunction occurred in 5 of 6 patients. Three patients had positive family history. Five patients had Addison's disease. Four patients were diagnosed as pure AMN, while the other two patients were with cerebral involvement. Four patients had abnormalities of nerve conduction studies. There were four patients with central conduction defects in somatosensory evoked potential tests. All 6 patients were found diffuse cord atrophy in spinal MRI. Brain MRI showed abnormal signals in 2 of the 6 tested patients, which indicated the clinical phenotypes. Plasma levels of VLCFA, as well as C24:0/C22:0 and C26:0/C22:0 ratios were elevated in 5 tested patients. Five different ABCD1 mutations were identified in 5 tested patients, one of which was a de novo mutation, and the other four have been reported previously. Conclusion This research described the clinical, neuroimaging, biochemical, and genetic sides of Chinese AMN patients. A de novo mutation in the ABCD1 gene sequence was identified. Emotional trauma may trigger or aggravate the development of cerebral demyelination in AMN patients. Regular evaluation of brain MRI is important for AMN patients, especially for ‘pure AMN’ patients. When encountering patients with ‘myeloneuropathy-only’, neurologists should not ignore the tests of VLCFA or/and the ABCD1 gene.

Background: Adrenoleukodystrophy is a rare neurogenetic disease,adrenomyeloneuropathy is the most common adult phenotype, such patients in China have not gotten enough attention.This article aims to study the features of AMN in Chinese patients and expand the gene spectrum of Chinese X-linked adrenoleukodystrophy (X-ALD) patients. Methods: We applied clinical analysis, radiology, plasma levels of very long chain fatty acids (VLCFA) and genetic analysis to test the 6 Chinese AMN patients. Results: All 6 patients are men. Ages of neurological symptom onset distributed between 21 and 38. Sexual dysfunction occurred in 5 of 6 patients. Three patients had positive family history. Five patients had Addison's disease. Four patients were diagnosed as pure AMN, the other two patients with cerebral involvement. Four patients have abnormalities of nerve conduction studies. There are four patients with central conduction defects in somatosensory evoked potential tests. All 6 patients found diffuse cord atrophy in spinal MRI. Brain MRI showed abnormal signals in 2 of the 6 tested patients, which indicated the clinical phenotypes. Plasma levels of VLCFA, as well as C24:0/C22:0 and C26:0/C22:0 ratios were elevated in 5 tested patients. Five different ABCD1 mutations were identified in 5 tested patients, one of which was a de novo mutation, and the other four have been reported previously. Conclusion: This research described the clinical, neuroimaging, biochemical, and genetic sides of Chinese AMN patients. A de novo mutation in the ABCD1 gene sequence was identified. Mental stimulation may trigger or aggravate the development of cerebral demyelination in AMN patients. Regular evaluation of brain MRI is important for AMN patients, especially for ‘pure AMN’ patients. When encountering patients with ‘myeloneuropathy-only’, neurologists should not ignore the tests of VLCFA or/and the ABCD1 gene. Keywords: Adrenomyeloneuropathy, Addison disease, Spastic paraparesis, Very long chain fatty acid, ABCD1.