Background Neuropathic pain (NeuP) is a chronic and challenging clinical problem, with little effective treatment. Resveratrol has shown neuroprotection by inhibiting inflammatory response in NeuP. Recently, the triggering receptor expressed on myeloid cells 2 (TREM2) expressed by microglia was identified as a critical factor of inflammation in nervous system diseases. In this study, we explored whether resveratrol could ameliorate neuroinflammation and produce anti-mechanical allodynia effects via regulating TREM2 in spared nerve injury rats, as well as investigated the underlying mechanisms. Methods A spared nerve injury (SNI) rat model was performed to investigate whether resveratrol could exert anti-mechanical allodynia effects via inhibiting neuroinflammation. To evaluate the role of TREM2 in anti-neuroinflammatory function of resveratrol, lentivirus coding TREM2 was intrathecally injected into SNI rats to activate TREM2, and the pain behavior was detected by the von Frey test. Furthermore, 3-methyladenine (3-MA, an autophagy inhibitor) was applied to study the molecular mechanisms of resveratrol-mediated anti-neuroinflammation using Western blot, qPCR, and immunofluorescence. Results The TREM2 expression and number of the microglial cells were significantly increased in the ipsilateral spinal dorsal horn after SNI. We found that intrathecal administration of resveratrol (300ug/day) alleviated mechanical allodynia; obviously enhanced autophagy; and markedly reduced the levels of interleukin-1β, interleukin-6, and tumor necrosis factor-α in the ipsilateral spinal dorsal horn after SNI. Moreover, the number of Iba-1+ microglial cells and TREM2 expression were downregulated after resveratrol treatment. Intrathecal administration of lentivirus coding TREM2 and/or 3-MA in those rats induced deficiencies in resveratrol-mediated anti-inflammation, leading to mechanical allodynia that could be rescued via administration of Res. Furthermore, 3-MA treatment contributed to TREM2-mediated mechanical allodynia. Conclusions Taken together, these data reveal that resveratrol relieves neuropathic pain through suppressing microglia-mediated neuroinflammation via regulating the TREM2-autophagy axis in SNI rats.

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Objective: Intermittent theta burst stimulation (iTBS) is a special form of repetitive transcranial magnetic stimulation (rTMS), which effectively increases cortical excitability and has been widely used as a neural modulation approach in stroke rehabilitation. As effects of iTBS are typically investigated by motor evoked potentials, how iTBS influences functional brain network following stroke remains unclear. Resting-state electroencephalography (EEG) has been suggested to be a sensitive measure for evaluating effects of rTMS on brain functional activity and network. Here, we used resting-state EEG to investigate the effects of iTBS on functional brain network in stroke survivors.Methods: We studied thirty stroke survivors (age: 63.1 ± 12.1 years; chronicity: 4.0 ± 3.8 months; UE FMA: 26.6 ± 19.4/66) with upper limb motor dysfunction. Stroke survivors were randomly divided into two groups receiving either Active or Sham iTBS over the ipsilesional primary motor cortex. Resting-state EEG was recorded at baseline and immediately after iTBS to assess the effects of iTBS on functional brain network.Results: Delta and theta bands interhemispheric functional connectivity were significantly increased after Active iTBS (P = 0.038 and 0.011, respectively), but were not significantly changed after Sham iTBS (P = 0.327 and 0.342, respectively). Delta and beta bands global efficiency were also significantly increased after Active iTBS (P = 0.013 and 0.0003, respectively), but not after Sham iTBS (P = 0.586 and 0.954, respectively).Conclusion: This is the first study that used EEG to investigate the acute neuroplastic changes after iTBS following stroke. Our findings for the first time provide evidence that iTBS modulates brain network functioning in stroke survivors. Acute increase in interhemispheric functional connectivity and global efficiency after iTBS suggest that iTBS has the potential to normalize brain network functioning following stroke, which can be utilized in stroke rehabilitation.