These findings suggest that reduced BDNF-TrkB signaling in the mPFC might contribute to neuropathic pain-induced anhedonia, and that TrkB agonists could be potential therapeutic drugs for pain-induced anhedonia.
Downregulated spinal IRF8 and BDNF in NAC are involved in neuropathic pain-induced depression relief via pulsed radiofrequency on dorsal root ganglion in rat SNI model.
Here, we aim to investigate whether PRF treatment could regulate the levels of BDNF, PI3K, and p-ERK in the spinal cord of rats with spared nerve injury (SNI) via suppressing the spinal microglia activation to ease neuropathic pain.
Using sortilin-deficient mice or receptor inhibition by antibodies or a small-molecule antagonist, we lastly demonstrate that we are able to fully block BDNF-induced pain and alleviate injury-induced neuropathic pain, validating sortilin as a clinically relevant target.
Mounting preclinical and clinical studies have shown neuropathic pain is highly associated with histone acetylation modification, which follows expression regulation of various pain-related molecules such as mGluR1/5, glutamate aspartate transporter, glutamate transporter-1, GAD65, Na<sub>v</sub>1.8, Kv4.3, μ-opioid receptor, brain-derived neurotrophic factor, and certain chemokines.
Our research findings confirm that cannabinoid treatment produces significant improvements in neurological disability scoring and behavioral assessments of NPP that directly result from their ability to reduce tumor necrosis factor alpha (TNF-α) production and enhance brain derived neurotrophic factor (BDNF) production.
Accordingly, the prolonged opposite changes of GSK-3β activity in hippocampus and in spinal dorsal horn induced by SNI may contribute to memory deficits and neuropathic pain by differential regulation of BDNF in the two regions.
Using a phototherapeutic approach based upon BDNF, the ligand for TrkB, we perform molecule-guided laser ablation of these neurons and achieve long-term retraction of TrkB-positive neurons from the skin and pronounced reversal of mechanical allodynia across multiple types of neuropathic pain.
It is noteworthy that ketamine (10 mg/kg) relieved neuropathic pain-induced depressive behaviors and restored alterations of BDNF and NLs in the mPFC and the hippocampus at 24 h and 72 h after the administration of ketamine, but only restored BDNF in the ACC.
These 2 P2XR subtypes differ pharmacologically and functionally: 1) P2X4Rs are activated at lower (≤0.1 mM) whereas P2X7Rs - at higher (≥1.0 mM) ATP concentrations; 2) P2X4R activation contributes to the release of brain derived neurotrophic factor and its role in tactile allodynia and neuropathic pain is demonstrated; 3) Due to its role in the secretion of pro-inflammatory IL-1β, P2X7Rs have been implicated in the development of neurodegenerative pathologies, pain and morphine tolerance.
Previously, we and others have documented that spinal brain-derived neurotrophic factor (BDNF), secreted from microglia, contributes to long-term potentiation (LTP) in adult rodents with neuropathic pain.
The development of neuropathic pain was related to the activation of glial cells, increased BDNF expression, and downregulation of the μ-opioid receptor in the ipsilateral spinal dorsal horn.
Finally, iTR significantly reduced microglial reactivity in LC and increased non-microglial BDNF expression, an effect that was reverted by butoxamine, implicating BDNF regulation in central 5HT/NE actions on neuropathic pain.
Here, we show that the complexity of excitatory synaptic connectivity and brain-derived neurotrophic factor (BDNF) expression are enhanced in SDH but reduced in the hippocampus in neuropathic pain and the opposite changes depend on tumor necrosis factor-alpha/tumor necrosis factor receptor 1 signaling and microglial activation.
In the present study, we investigated the vital roles of miR-206 and its putative target gene, brain-derived neurotrophic factor (BDNF), in neuropathic pain in the rat model of chronic constriction injury (CCI).
These findings suggest that alterations in the inflammatory cytokines and BDNF might contribute to neuropathic pain-induced depression, and that serum cytokines may be predictable biomarkers for ketamine's antidepressant actions.
Therefore, the BDNF-Fyn-GluN2B signaling cascade in the spinal dorsal horn may constitute a key mechanism underlying central sensitization and neuropathic pain development after peripheral nerve injury.
It has been suggested that the disruption of complex behaviors and mood seen in some neuropathic pain patients is mediated in part by alterations of BDNF in this cortical region.
The present study shows that depression attenuates the mechanical allodynia and thermal hyperalgesia of neuropathic pain and suggests that altered spinal GR-BDNF-TrkB signaling may be one of the reasons for depression-induced hypoalgesia.
In conclusion, we demonstrate, for the first time, that ERK is an important downstream effector of the BDNF/TrkB-mediated signalling pathway in the rACC that contributes to the development of neuropathic pain-related aversion.
Together, our data indicate that trkB.T1 in astrocytes contributes to neuropathic pain and neurological dysfunction following SCI, suggesting that trkB.T1 may provide a novel therapeutic target for SCI.<b>SIGNIFICANCE STATEMENT</b> Neuropathic pain after spinal cord injury (SCI) may in part be caused by upregulation of the brain-derived neurotrophic factor (BDNF) receptor trkB.T1, a truncated isoform of BDNF.