Neuropathic pain is a complex, chronic pain state characterized by hyperalgesia, allodynia, and spontaneous pain. Accumulating evidence has indicated that the microglial Toll-like receptor 4 (TLR4) and autophagy are implicated in neurodegenerative diseases, but their relationship and role in neuropathic pain remain unclear. In this study, we examined TLR4 and its association with autophagic activity using a chronic constriction injury (CCI)-induced neuropathic pain model in wild-type (WT) and TLR4-knockout (KO) mice. The mice were assigned into four groups: WT-Contralateral (Contra), WT-Ipsilateral (Ipsi), TLR4 KO-Contra, and TLR4 KO-Ipsi. Behavioral and mechanical allodynia tests and biochemical analysis of spinal cord tissue were conducted following CCI to the sciatic nerve. Compared with the Contra group, mechanical allodynia in both the WT- and TLR4 KO-Ipsi groups was significantly increased, and a marked decrease of allodynia was observed in the TLR4 KO-Ipsi group. Although glial cells were upregulated in the WT-Ipsi group, no significant change was observed in the TLR4 KO groups. Moreover, protein expression and immunoreactive cell regulation of autophagy (Beclin 1, p62) were significantly increased in the neurons, but not microglia, of WT-Ipsi group compared with the WT-Contra group. The level of PINK1, a marker for mitophagy was increased in the neurons of WT, but not in TLR4 KO mice. Together, these results show that TLR4-mediated p62 autophagic impairment plays an important role in the occurrence and development of neuropathic pain. And what is more, microglial TLR4-mediated microglial activation might be indirectly coupled to neuronal autophage.

Therapeutic, V.

BackgroundThe goal of this study was to investigate the anatomy of the peroneal artery and its perforators, and to report the clinical results of reconstruction with peroneal artery perforator flaps.MethodsThe authors dissected 4 cadaver legs and investigated the distribution, course, origin, number, type, and length of the perforators. Peroneal artery perforator flap surgery was performed on 29 patients.ResultsWe identified 19 perforators in 4 legs. The mean number of perforators was 4.8 per leg, and the mean length was 4.8 cm. Five perforators were found proximally, 9 medially, and 5 distally. We found 12 true septocutaneous perforators and 7 musculocutaneous perforators. Four emerged from the posterior tibia artery, and 15 were from the peroneal artery. The peroneal artery perforator flap was used in 29 patients. Retrograde island peroneal flaps were used in 8 cases, anterograde island peroneal flaps in 5 cases, and free peroneal flaps in 16 cases. The mean age was 59.9 years, and the defect size ranged from 2.0 cm×4.5 cm to 8.0 cm×8.0 cm. All the flaps survived. Five flaps developed partial skin necrosis. In 2 cases, a split-thickness skin graft was performed, and the other 3 cases were treated without any additional procedures.ConclusionsThe peroneal artery perforator flap is a good alternative for the reconstruction of soft tissue defects, with a constant and reliable vascular pedicle, thin and pliable skin, and the possibility of creating a composite tissue flap.

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