Insular cortex stimulation alleviates neuropathic pain via ERK phosphorylation in neurons.

AIMS: The clinical use of brain stimulation is attractive for patients who have side effects or tolerance. However, studies on insular cortex (IC) stimulation are lacking in neuropathic pain. The present study aimed to investigate the effects of IC stimulation (ICS) on neuropathic pain and to determine how ICS modulates pain. METHODS: Changes in pain behaviors were observed following ICS with various parameters in neuropathic rats. Western blotting was performed to assess molecular changes in the expression levels of phosphorylated extracellular signal-regulated kinase (pERK), neurons, astrocytes, and microglia between experimental groups. Immunohistochemistry was performed to investigate the colocalization of pERK with different cell types. RESULTS: The most effective pain-relieving effect was induced at 50 Hz-120 µA in single trial of ICS and it maintained 4 days longer after the termination of repetitive ICS. The expression levels of pERK, astrocytes, and microglia were increased in neuropathic rats. However, after ICS, the expression levels of pERK were decreased, and colocalization of pERK and neurons was reduced in layers 2-3 of the IC. CONCLUSION: These results indicated that ICS attenuated neuropathic pain by the regulation of pERK in neurons located in layers 2-3 of the IC. This preclinical study may enhance the potential use of ICS and identify the therapeutic mechanisms of ICS in neuropathic pain.

Diffusion tensor imaging reveals sex differences in pain sensitivity of rats.

Studies on differences in brain structure and function according to sex are reported to contribute to differences in behavior and cognition. However, few studies have investigated brain structures or used tractography to investigate gender differences in pain sensitivity. The identification of tracts involved in sex-based structural differences that show pain sensitivity has remained elusive to date. Here, we attempted to demonstrate the sex differences in pain sensitivity and to clarify its relationship with brain structural connectivity. In this study, pain behavior test and brain diffusion tensor imaging (DTI) were performed in male and female rats and tractography was performed on the whole brain using fiber tracking software. We selected eight brain regions related to pain and performed a tractography analysis of these regions. Fractional anisotropy (FA) measurements using automated tractography revealed sex differences in the anterior cingulate cortex (ACC)-, prefrontal cortex (PFC)-, and ventral posterior thalamus-related brain connections. In addition, the results of the correlation analysis of pain sensitivity and DTI tractography showed differences in mean, axial, and radial diffusivities, as well as FA. This study revealed the potential of DTI for exploring circuits involved in pain sensitivity. The behavioral and functional relevance's of measures derived from DTI tractography is demonstrated by their relationship with pain sensitivity.