Altered mRNA expression after long-term soleus electrical stimulation training in humans with paralysis

Abstract Objectives Chronic stress activates danger-associated molecular patterns (DAMPs), stimulating the NLRP3 inflammasome. NLRP3 activation triggers the release of pro-inflammatory cytokine IL-1β. The activity of the NLRP3 inflammasome propagates pro-inflammatory signaling cascades implicated in the onset of depression. Our previous studies show that polyphenolic compounds were found to ameliorate stress induced depression in mouse models. However, the relevant mechanism has not been identified. This study examined the effect of administering polyphenols on DAMP signaling in enriched mice microglia. Methods This study examined the effect of administering polyphenols on DAMP signaling in mice microglia. To recapitulate stress-induced depression, mice underwent chronic unpredictable stress (CUS). Microglia were isolated at various time points throughout the CUS protocol. We also assessed long-term persistent changes after CUS and susceptibility to subthreshold unpredictable stress (US) re-exposure. Results Interestingly, the development of US – induced depression and anxiety depended upon a previous exposure to CUS. We found that CUS caused robust upregulation of IL-1β mRNA in enriched microglia, an effect that persists for up to 4 weeks following CUS exposure. Following the subthreshold US re-exposure, we observed the upregulation of pro- IL-1β as well as pro-receptor for advanced glycation end products (RAGE). Toll-like receptor 4 (TLR-4) was not. We also observed an increase in RAGE mRNA expression when mice were exposed to US prior to the start of the CUS paradigm. Importantly, a primary exposure to US, was sufficient to increase RAGE mRNA expression. We found that polyphenol administration significantly improved CUS-induced depressive-like phenotypes and also reversed neuroinflammation in mice. Treatment with dietary flavonoids prevented upregulation of IL-1β, RAGE mRNA, which reflects the ability of polyphenols that may have begun following the primary exposure to US. Conclusions Taken all together, the results provide evidence of the role of dietary polyphenols in preventing persistent microglial activation, which has been shown to result in reduced long term vulnerability to depressive-like behaviors following expose to chronic stress. Funding Sources This study was supported by a P50 CARBON Center grant from the NCCIH/ODS.

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Electrical stimulation of referred sensation area alleviates phantom limb pain

Restorative Neurology and Neuroscience ◽

10.3233/rnn-201132 ◽

2021 ◽

pp. 1-10

Author(s):

Michihiro Osumi ◽

Daisuke Shimizu ◽

Yuki Nishi ◽

Shu Morioka

Keyword(s):

Electrical Stimulation ◽

Single Case ◽

Phantom Limb Pain ◽

Phantom Limb ◽

Long Term Effects ◽

Limb Pain ◽

Short Term ◽

Analgesic Effects ◽

Stimulation Of

Background: Patients with brachial plexus avulsion (BPA) usually experience phantom sensations and phantom limb pain (PLP) in the deafferented limb. It has been suggested that evoking the sensation of touch in the deafferented limb by stimulating referred sensation areas (RSAs) on the cheek or shoulder might alleviate PLP. However, feasible rehabilitation techniques using this approach have not been reported. Objective: The present study sought to examine the analgesic effects of simple electrical stimulation of RSAs in BPA patients with PLP. Methods: Study 1: Electrical stimulation of RSAs for 60 minutes was conducted for six BPA patients suffering from PLP to examine short-term analgesic effects. Study 2: A single case design experiment was conducted with two BPA patients to investigate whether electrical stimulation of RSAs was more effective for alleviating PLP than control electrical stimulation (electrical stimulation of sites on side opposite to the RSAs), and to elucidate the long-term effects of electrical stimulation of RSAs. Results: Study 1: Electrical stimulation of RSAs evoked phantom touch sensations in the deafferented limb, and significantly alleviated PLP (p < 0.05). Study 2: PLP was alleviated more after electrical stimulation on RSAs compared with control electrical stimulation (p < 0.05). However, the analgesic effects of electrical stimulation on RSAs were observed only in the short term, not in the long term (p > 0.05). Conclusions: Electrical stimulation of RSAs not only evoked phantom touch sensation but also alleviated PLP in the short term. The results indicate that electrical stimulation of RSAs may provide a useful practical rehabilitation technique for PLP. Future studies will be required to clarify the mechanisms underlying immediate PLP alleviation via electrical stimulation of RSAs.

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