Dataset Information

Role of neuregulin-1/ErbB signaling in stem cell therapy for spinal cord injury-induced chronic neuropathic pain.

ABSTRACT: Chronic neuropathic pain is a common and debilitating consequence of spinal cord injury (SCI). In a rat contusion injury model, we observed that chronic neuropathic pain is present on day 7 after SCI and persists for the entire 56-day observation period. However, currently available pain therapies are inadequate for SCI-induced neuropathic pain. In this study, we show that spinal transplantation of mouse embryonic stem cell-derived oligodendrocyte progenitor cells (OPCs) enhances remyelination in the injured spinal cord and reduces SCI-induced chronic neuropathic pain. Moreover, we found that SCI reduces the protein level of neuregulin-1 and ErbB4 in the injured spinal cord and that OPC transplantation enhances the spinal expression of both proteins after SCI. Finally, intrathecal injection of neuregulin-1 small interfering RNA, but not the control nontarget RNA, diminishes OPC transplantation-produced remyelination and reverses the antinociceptive effect of OPC transplantation. Our findings suggest that the transplantation of embryonic stem cell-derived OPCs is an appropriate therapeutic intervention for treatment of SCI-induced chronic neuropathic pain, and that neuregulin-1/ErbB signaling plays an important role in central remyelination under pathological conditions and contributes to the alleviation of such pain.

SUBMITTER: Tao F

PROVIDER: S-EPMC3682663 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature

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Role of neuregulin-1/ErbB signaling in stem cell therapy for spinal cord injury-induced chronic neuropathic pain.

Tao Feng F Li Qun Q Liu Su S Wu Haiying H Skinner John J Hurtado Andres A Belegu Visar V Furmanski Orion O Yang Ya Y McDonald John W JW Johns Roger A RA

Stem cells (Dayton, Ohio) 20130101 1

Chronic neuropathic pain is a common and debilitating consequence of spinal cord injury (SCI). In a rat contusion injury model, we observed that chronic neuropathic pain is present on day 7 after SCI and persists for the entire 56-day observation period. However, currently available pain therapies are inadequate for SCI-induced neuropathic pain. In this study, we show that spinal transplantation of mouse embryonic stem cell-derived oligodendrocyte progenitor cells (OPCs) enhances remyelination i ...[more]

PMID: 23097328

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Project description:BackgroundCentral sensitization is considered a key mechanism underlying neuropathic pain (NP) after spinal cord injury (SCI).MethodsTwo novel proxies for central sensitization were investigated in thoracic SCI subjects with (SCI-NP) and without NP (SCI-nonNP) compared to healthy controls (HC). Specifically, temporal summation of pain (TSP) was investigated by examining pain ratings during a 2-min tonic heat application to the volar forearm. Additionally, palmar heat-induced sympathetic skin responses (SSR) were recorded in order to reveal changes in pain-autonomic interaction above the lesion level. Pain extent was assessed as the percentage of the body area and the number of body regions being affected by NP.ResultsEnhanced TSP was observed in SCI-NP (+66%) compared to SCI-nonNP (-75%, p = 0.009) and HC (-59%, p = 0.021). In contrast, no group differences were found (p = 0.685) for SSR habituation. However, pain extent in SCI-NP was positively correlated with deficient SSR habituation (body area: r = 0.561, p = 0.024; body regions: r = 0.564, p = 0.023).ConclusionsThese results support the value of TSP and heat-induced SSRs as proxies for central sensitization in widespread neuropathic pain syndromes after SCI. Measures of pain-autonomic interaction emerged as a promising tool for the objective investigation of sensitized neuronal states in chronic pain conditions.SignificanceWe present two surrogate readouts for central sensitization in neuropathic pain following SCI. On the one hand, temporal summation of tonic heat pain is enhanced in subjects with neuropathic pain. On the other hand, pain-autonomic interaction reveals potential advanced measures in chronic pain, as subjects with a high extent of neuropathic pain showed diminished habituation of pain-induced sympathetic measures. A possible implication for clinical practice is constituted by an improved assessment of neuronal hyperexcitability potentially enabling mechanism-based treatment.

Project description:BackgroundNeurofeedback (NFB) is a neuromodulatory technique that enables voluntary modulation of brain activity in order to treat neurological condition, such as central neuropathic pain (CNP). A distinctive feature of this technique is that it actively involves participants in the therapy. In this feasibility study, we present results of participant self-managed NFB treatment of CNP.MethodsFifteen chronic spinal cord injured (SCI) participants (13M, 2F), with chronic CNP equal or greater than 4 on the Visual Numeric Scale, took part in the study. After initial training in hospital (up to 4 sessions), they practiced NF at home, on average 2-3 times a week, over a period of several weeks (min 4, max 20). The NFB protocol consisted of upregulating the alpha (9-12 Hz) and downregulating the theta (4-8 Hz) and the higher beta band (20-30 Hz) power from electrode location C4, for 30 min. The output measures were pain before and after NFB, EEG before and during NFB and pain questionnaires. We analyzed EEG results and show NFB strategies based on the Power Spectrum Density of each single participant.ResultsTwelve participants achieved statistically significant reduction in pain and in eight participants this reduction was clinically significant (larger than 30%). The most successfully regulated frequency band during NFB was alpha. However, most participants upregulated their individual alpha band, that had an average dominant frequency at αp = 7.6 ± 0.8 Hz (median 8 Hz) that is lower than the average of the general population, which is around 10 Hz. Ten out of fifteen participants significantly upregulated their individual alpha power (αp ± 2 Hz) as compared to 4 participants who upregulated the power in the fixed alpha band (8-12 Hz). Eight out of the twelve participants who achieved a significant reduction of pain, significantly upregulated their individual alpha band power. There was a significantly larger increase in alpha power (p < 0.0001) and decrease of theta power (p < 0.04) in participant specific rather than in fixed frequency bands.ConclusionNeurofeedback is a neuromodulatory technique that gives participants control over their pain and can be self-administered at home. Regulation of individual frequency band was related to a significant reduction in pain.

Dataset Information

Role of neuregulin-1/ErbB signaling in stem cell therapy for spinal cord injury-induced chronic neuropathic pain.

Publications

Role of neuregulin-1/ErbB signaling in stem cell therapy for spinal cord injury-induced chronic neuropathic pain.

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