Non‐neuronal BDNF, a key player in development of central sensitization and neuropathic pain

Boudes, Mathieu; Menigoz, Aurelie

doi:10.1113/jphysiol.2009.172130

Cited by 14 publications

(6 citation statements)

References 5 publications

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“…An extensive amount of research has shown that BDNF levels increase after exercise in both healthy subjects (48) and patients with FM (26), and several different mechanisms can induce BDNF release from the brain and spinal cord after physical activity (25). In addition, BDNF expression from either neuronal or nonneuronal cells is able to induce central sensitization and hyperalgesia (10,58). Although the present study did not include an exercise challenge, our findings show that BDNF expression is higher at baseline in patients with CFS/FM than in sedentary healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation and Brain‐Derived Neurotrophic Factor Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Comorbid Fibromyalgia

Polli

Ghosh

Bakusic

et al. 2020

Arthritis & Rheumatology

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Objective The epigenetics of neurotrophic factors holds the potential to unravel the mechanisms underlying the pathophysiology of complex conditions such as chronic fatigue syndrome (CFS). This study was undertaken to explore the role of brain‐derived neurotrophic factor (BDNF) genetics, epigenetics, and protein expression in patients with both CFS and comorbid fibromyalgia (CFS/FM). Methods A repeated‐measures study was conducted in 54 participants (28 patients with CFS/FM and 26 matched healthy controls). Participants underwent a comprehensive assessment, including questionnaires, sensory testing, and blood withdrawal. Serum BDNF (sBDNF) protein levels were measured using enzyme‐linked immunosorbent assay, while polymorphism and DNA methylation were measured in blood using pyrosequencing technology. To assess the temporal stability of the measures, participants underwent the same assessment twice within 4 days. Results Repeated‐measures mixed linear models were used for between‐group analysis, with mean differences and 95% confidence intervals (95% CIs) shown. Compared to controls, serum BNDF was higher in patients with CFS/FM (F = 15.703; mean difference 3.31 ng/ml [95% CI 1.65, 4.96]; P = 0.001), whereas BDNF DNA methylation in exon 9 was lower (F = 7.543; mean difference −2.16% [95% CI −3.93, −0.83]; P = 0.007). BDNF DNA methylation was mediated by the Val66Met (rs6265) polymorphism. Lower methylation in the same region predicted higher sBDNF levels (F = 7.137, β = −0.408 [95% CI −0.711, −0.105]; P = 0.009), which in turn predicted participants’ symptoms (F = 14.410, β = 3.747 [95% CI 1.79, 5.71]; P = 0.001) and widespread hyperalgesia (F = 4.147, β = 0.04 [95% CI 0.01, 0.08]; P = 0.044). Conclusion Our findings indicate that sBDNF levels are elevated in patients with CFS/FM and that BDNF methylation in exon 9 accounts for the regulation of protein expression. Altered BDNF levels might represent a key mechanism explaining CFS/FM pathophysiology.

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Section: Discussionmentioning

confidence: 99%

DNA Methylation and Brain‐Derived Neurotrophic Factor Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Comorbid Fibromyalgia

Polli

Ghosh

Bakusic

et al. 2020

Arthritis & Rheumatology

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“…Systemic activation of BDNF is associated with the development of chronic pain, obesity, and altered liver glucose regulation. [16][17][18] Many of the growth factors or cytokines that stimulate neural repair in pre-clinical models have widespread effects in other body tissues, such as erythropoietin, fibroblast growth factor, and G-CSF. In pre-clinical studies, these molecules stimulated axonal sprouting, neurogenesis, and other aspects of neural repair.…”

Section: Introductionmentioning

confidence: 99%

Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke

Cook

Nguyen

Chun

et al. 2016

J Cereb Blood Flow Metab

164

131

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Stroke is the leading cause of adult disability. Systemic delivery of candidate neural repair therapies is limited by the blood-brain barrier and off-target effects. We tested a bioengineering approach for local depot release of BDNF from the infarct cavity for neural repair in chronic periods after stroke. The brain release levels of a hyaluronic acid hydrogel þ BDNF were tested in several stroke models in mouse (strains C57Bl/6, DBA) and non-human primate (Macaca fascicularis) and tracked with MRI. The behavioral recovery effects of hydrogel þ BDNF and the effects on tissue repair outcomes were determined. Hydrogel-delivered BDNF diffuses from the stroke cavity into peri-infarct tissue over 3 weeks in two mouse stroke models, compared with 1 week for direct BDNF injection. Hydrogel delivery of BDNF promotes recovery of motor function. Mapping of motor system connections indicates that hydrogel-BDNF induces axonal sprouting within existing cortical and cortico-striatal systems. Pharmacogenetic studies show that hydrogel-BDNF induces the initial migration of immature neurons into the peri-infarct cortex and their long-term survival. In chronic stroke in the non-human primate, hydrogel-released BDNF can be detected up to 2 cm from the infarct, a distance relevant to human functional recovery in stroke. The hydrogel can be tracked by MRI in mouse and primate.

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“…To increase our understanding of the function of TrkB.T1, we developed a TrkB.T1-specific knockout mouse [40]; the absence of TrkB.T1 reduced the development of allodynia and thermal hyperalgesia in these model systems, respectively [29]. As we [26] and others [117] have demonstrated that the BDNF increase in SDH following chemotherapy or surgical nerve injury produces hyperexcitability of WDR neurons in the dorsal horn, we therefore examined whether there were differences in neuronal excitability after hind paw inflammation in TrkB.T1 null versus wildtype (WT) mice. As shown in Figure 2, WDR neuronal excitability in the CFA-treated KO mice was no different than vehicle-treated WT mice.…”

Section: Bdnf/trkbt1 Regulation In Neuropathic Painmentioning

confidence: 99%

Function and Mechanisms of Truncated BDNF Receptor TrkB.T1 in Neuropathic Pain

Cao

Matyas

Renn

et al. 2020

Cells

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Brain-derived neurotrophic factor (BDNF), a major focus for regenerative therapeutics, has been lauded for its pro-survival characteristics and involvement in both development and recovery of function within the central nervous system (CNS). However, studies of tyrosine receptor kinase B (TrkB), a major receptor for BDNF, indicate that certain effects of the TrkB receptor in response to disease or injury may be maladaptive. More specifically, imbalance among TrkB receptor isoforms appears to contribute to aberrant signaling and hyperpathic pain. A truncated isoform of the receptor, TrkB.T1, lacks the intracellular kinase domain of the full length receptor and is up-regulated in multiple CNS injury models. Such up-regulation is associated with hyperpathic pain, and TrkB.T1 inhibition reduces neuropathic pain in various experimental paradigms. Deletion of TrkB.T1 also limits astrocyte changes in vitro, including proliferation, migration, and activation. Mechanistically, TrkB.T1 is believed to act through release of intracellular calcium in astrocytes, as well as through interactions with neurotrophins, leading to cell cycle activation. Together, these studies support a potential role for astrocytic TrkB.T1 in hyperpathic pain and suggest that targeted strategies directed at this receptor may have therapeutic potential.

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Non‐neuronal BDNF, a key player in development of central sensitization and neuropathic pain

Cited by 14 publications

References 5 publications

DNA Methylation and Brain‐Derived Neurotrophic Factor Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Comorbid Fibromyalgia

DNA Methylation and Brain‐Derived Neurotrophic Factor Expression Account for Symptoms and Widespread Hyperalgesia in Patients With Chronic Fatigue Syndrome and Comorbid Fibromyalgia

Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke

Function and Mechanisms of Truncated BDNF Receptor TrkB.T1 in Neuropathic Pain

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