Increased EZH2 Levels in Anterior Cingulate Cortex Microglia Aggravate Neuropathic Pain by Inhibiting Autophagy Following Brachial Plexus Avulsion in Rats.
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SUBMITTER: Meng XL
PROVIDER: S-EPMC7340721 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Objective: The present study aimed to investigate the analgesic effect of electroacupuncture (EA) in neuropathic pain due to brachial plexus avulsion injury (BPAI) and related changes in the metabolic brain connectivity. Methods: Neuropathic pain model due to BPAI was established in adult female Sprague-Dawley rats. EA stimulations (2/15 Hz, 30 min/day, 5-day intervention followed by 2-day rest in each session) were applied to the fifth-seventh cervical "Jiaji" acupoints on the noninjured side from 1st to 12th weeks following BPAI (EA group, n = 8). Three control groups included sham EA (nonelectrical acupuncture applied to 3 mm lateral to the real "Jiaji" acupoints), BPAI-only, and normal rats (no particular intervention; eight rats in each group). Thermal withdrawal latency (TWL) of the noninjured forepaw was regularly tested to evaluate the threshold of thermalgesia. Small animal [fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) PET/CT scans of brain were conducted at the end of 4th, 12th, and 16th weeks to explore metabolic alterations of brain. Results: In the EA group, the TWL of the noninjured forepaw significantly decreased following BPAI and then increased following EA stimulation, compared with sham EA (P < 0.001). The metabolic brain connectivity among somatosensory cortex (SC), motor cortex (MC), caudate putamen (Cpu), and dorsolateral thalamus (DLT) in bilateral hemispheres decreased throughout the 16 weeks' observation in the BPAI-only group, compared with the normal rats (P < 0.05). In the EA group, the strength of connectivity among the above regions were found to be increased at the end of 4th week following BPAI modeling, decreased at 12th week, and then increased again at 16th week (P < 0.05). The changes in metabolic connectivity were uncharacteristic and dispersed in the sham EA group. Conclusion: The study revealed long-term and extensive changes of metabolic brain connectivity in EA-treated BPAI-induced neuropathic pain rats. Bilateral sensorimotor and pain-related brain regions were mainly involved in this process. It indicated that modulation of brain metabolic connectivity might be an important mechanism of analgesic effect in EA stimulation for the treatment of neuropathic pain.
| S-EPMC7313422 | biostudies-literature
Project description:BackgroundMany studies have shown the antinociceptive effects of cannabinoid (CB) agonists in different models of pain. Herein, we have investigated their relevance in neuropathic pain induced by brachial plexus avulsion (BPA) in mice.Methodology/principal findingsMice underwent BPA or sham surgery. The mRNA levels and protein expression of CB(1) and CB(2) receptors were assessed by RT-PCR and immunohistochemistry, respectively. The activation of glial cells, MAP kinases and transcription factors were evaluated by immunohistochemistry. The antinociceptive properties induced by cannabinoid agonists were assessed on the 5(th) and 30(th) days after surgery. We observed a marked increase in CB(1) and CB(2) receptor mRNA and protein expression in the spinal cord and dorsal root ganglion, either at the 5(th) or 30(th) day after surgery. BPA also induced a marked activation of p38 and JNK MAP kinases (on the 30(th) day), glial cells, such as microglia and astrocytes, and the transcription factors CREB and NF-κB (at the 5(th) and 30(th) days) in the spinal cord. Systemic treatment with cannabinoid agonists reduced mechanical allodynia on both the 5(th) and 30(th) days after surgery, but the greatest results were observed by using central routes of administration, especially at the 30(th) day. Treatment with WIN 55,212-2 prevented the activation of both glial cells and MAP kinases, associated with an enhancement of CREB and NF-κB activation.Conclusions/significanceOur results indicate a relevant role for cannabinoid agonists in BPA, reinforcing their potential therapeutic relevance for the management of chronic pain states.
| S-EPMC3172222 | biostudies-literature
Project description:Introduction: Although transcranial direct current stimulation (tDCS) and mirror therapy (MT) have benefits in combating chronic pain, there is still no evidence of the effects of the simultaneous application of these techniques in patients with neuropathic pain. This study aims to assess the efficacy of tDCS paired with MT in neuropathic pain after brachial plexus injury. Methods: In a sham controlled, double-blind, parallel-group design, 16 patients were randomized to receive active or sham tDCS administered during mirror therapy. Each patient received 12 treatment sessions, 30 min each, during a period of 4 weeks over M1 contralateral to the side of the injury. Outcome variables were evaluated at baseline and post-treatment using the McGill questionnaire, Brief Pain Inventory, and Medical Outcomes Study 36-Item Short-Form Health Survey. Long-term effects of treatment were evaluated at a 3-month follow-up. Results: An improvement in pain relief and quality of life were observed in both groups (p ≤ 0.05). However, active tDCS and mirror therapy resulted in greater improvements after the endpoint (p ≤ 0.02). No statistically significant differences in the outcome measures were identified among the groups at follow-up (p ≥ 0.12). A significant relationship was found between baseline pain intensity and outcome measures (p ≤ 0.04). Moreover, the results showed that state anxiety is closely linked to post-treatment pain relief (p ≤ 0.05). Conclusion: Active tDCS combined with mirror therapy has a short-term effect of pain relief, however, levels of pain and anxiety at the baseline should be considered. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT04385030.
| S-EPMC7759497 | biostudies-literature
Project description:BackgroundsThere is considerable evidence that central nervous system is continuously modulated by activity, behavior and skill acquisition. This study is to examine the reorganization in cortical and subcortical regions in response to brachial plexus avulsion.MethodsAdult C57BL/6 mice were divided into four groups: control, 1, 3 and 6 month of brachial plexus avulsion. IL-1?, IL-6 and RGS4 expression in cortex, brainstem and spinal cord were detected by BiostarM-140 s microarray and real-time PCR. RGS4 subcellular distribution and modulation were further analyzed by primary neuron culture and Western Blot.ResultsAfter 1, 3 and 6 months of brachial plexus avulsion, 49 (0 up, 49 down), 29 (17 up, 12 down), 13 (9 up, 4 down) genes in cerebral cortex, 40 (8 up, 32 down), 11 (7 up, 4 down), 137 (63 up, 74 down) in brainstem, 27 (14 up, 13 down), 33 (18 up, 15 down), 60 (29 up, 31 down) in spinal cord were identified. Among the regulated gene, IL-1? and IL-6 were sustainable enhanced in brain stem, while PKAC? and RGS4 were up-regulated throughout cerebral cortex, brainstem and spinal cord in 3 and 6 month of nerve injury. Intriguingly, subcellular distribution of RGS4 in above three regions was dependent on the functional correlation of PKA and IL-1?.ConclusionData herein indicated that brachial plexus avulsion could efficiently initiate and perpetuate the brain reorganization. Network involved IL-1? and RGS4 signaling might implicate in the re-establish and strengthening of the local circuits at the cortical and subcortical levels.
| S-EPMC3017042 | biostudies-literature
Project description:Global brachial plexopathies including multiple nerve root avulsions may result in complete upper limb paralysis despite surgical treatment. Bionic reconstruction, which includes the elective amputation of the functionless hand and its replacement with a mechatronic device, has been described for the transradial level. Here, we present for the first time that patients with global brachial plexus avulsion injuries and lack of biological shoulder and elbow function benefit from above-elbow amputation and prosthetic rehabilitation. Between 2012 and 2017, forty-five patients with global brachial plexus injuries approached our centre, of which nineteen (42.2%) were treated with bionic reconstruction. While fourteen patients were amputated at the transradial level, the entire upper limb was replaced with a prosthetic arm in a total of five patients. Global upper extremity function before and after bionic arm substitution was assessed using two objective hand function tests, the action research arm test (ARAT), and the Southampton hand assessment procedure (SHAP). Other outcome measures included the DASH questionnaire, VAS to assess deafferentation pain and the SF-36 health survey to evaluate changes in quality of life. Using a hybrid prosthetic arm mean ARAT scores improved from 0.6 ± 1.3 to 11.0 ± 6.7 (p = 0.042) and mean SHAP scores increased from 4.0 ± 3.7 to 13.8 ± 9.2 (p = 0.058). After prosthetic arm replacement mean DASH scores improved from 52.5 ± 9.4 to 31.2 ± 9.8 (p = 0.003). Deafferentation pain decreased from mean VAS 8.5 ± 1.0 to 6.7 ± 2.1 (p = 0.055), while the physical and mental component summary scale as part of the SF-36 health survey improved from 32.9 ± 6.4 to 40.4 ± 9.4 (p = 0.058) and 43.6 ± 8.9 to 57.3 ± 5.5 (p = 0.021), respectively. Bionic reconstruction can restore simple but robust arm and hand function in longstanding brachial plexus patients with lack of treatment alternatives.
| S-EPMC7019829 | biostudies-literature
Project description:IntroductionBrachial plexus avulsion (BPA) injury develops frequent and intense neuropathic pain, involving in both peripheral and central nervous systems. The incidence of anxiety or depression caused by BPA-induced neuropathic pain is high, but the underlying mechanism remains unclear.MethodsWe established a BPA mice model and assessed its negative emotions through behavioral tests. To further explore the role of the microbiota-gut-brain axis in the unique emotional behavior after BPA, we performed intestinal fecal 16s and metabolomics assays. Psychobiotics (PB) supplementation was administered to BPA mice to check the probiotics effects on BPA-induced anxiety behaviors.ResultsPain related anxiety-like behavior was observed at the early stage after BPA (7 days), while no depression-like behavior was detected. Intriguingly, gut microbiota diversity was increased in BPA mice, and the most abundant probiotics, Lactobacillus, showed obvious changes. Lactobacillus_reuteri was significantly decreased in BPA mice. Metabolomics analysis showed that Lactobacillus_reuteri-related bile acid pathway and some neurotransmitter amino acids were significantly altered. Further PB (dominated by Lactobacillus_reuteri) supplementation could significantly relieve BPA-induced anxiety-like behaviors in mice.ConclusionOur study suggests that pathological neuralgia after BPA could alter intestinal microbiota diversity, especially Lactobacillus, and the changes in neurotransmitter amino acid metabolites may be the key reason for the onset of anxiety-like behaviors in BPA mice.
| S-EPMC9944865 | biostudies-literature
Project description:Despite recent great progress in diagnosis and microsurgical repair, the prognosis in total brachial plexus-avulsion injury remains unfavorable. Insufficient number of donors and unreasonable use of donor nerves might be key factors. To identify an optimal treatment strategy for this condition, we conducted a retrospective review. Seventy-three patients with total brachial plexus avulsion injury were followed up for an average of 7.3 years. Our analysis demonstrated no significant difference in elbow-flexion recovery between phrenic nerve-transfer (25 cases), phrenic nerve-graft (19 cases), intercostal nerve (17 cases), or contralateral C7-transfer (12 cases) groups. Restoration of shoulder function was attempted through anterior accessory nerve (27 cases), posterior accessory nerve (10 cases), intercostal nerve (5 cases), or accessory + intercostal nerve transfer (31 cases). Accessory nerve + intercostal nerve transfer was the most effective method. A significantly greater amount of elbow extension was observed in patients with intercostal nerve transfer (25 cases) than in those with contralateral C7 transfer (10 cases). Recovery of median nerve function was noticeably better for those who received entire contralateral C7 transfer (33 cases) than for those who received partial contralateral C7 transfer (40 cases). Wrist and finger extension were reconstructed by intercostal nerve transfer (31 cases). Overall, the recommended surgical treatment for total brachial plexus-avulsion injury is phrenic nerve transfer for elbow flexion, accessory nerve + intercostal nerve transfer for shoulder function, intercostal nerves transfer for elbow extension, entire contralateral C7 transfer for median nerve function, and intercostal nerve transfer for finger extension. The trial was registered at ClinicalTrials.gov (identifier: NCT03166033).
| S-EPMC5900510 | biostudies-literature
Project description:Background and purposeBrachial plexus birth injury is caused by traction on the neck during delivery and results in flaccid palsy of an upper extremity commonly involving C5-C6 nerve roots. MR imaging and MR myelography help to assess the anatomic location, extent, and severity of brachial plexus injuries which influence the long-term prognosis along with the surgical decision making. Recently, sonography has been increasingly used as the imaging modality of choice for brachial plexus injuries. The aim of this study was to assess the degree of correlation among brachial plexus sonography, MR imaging, and surgical findings in children with brachial plexus birth injury.Materials and methodsThis prospective study included 55 consecutive patients (girls/boys = 32:23; mean age, 2.1 ± 0.8 months) with brachial plexus birth injury between May 2014 and April 2017. The patients were classified according to the Narakas classification and were followed up at 4- to 6-week intervals for recovery by the Modified Mallet system and sonography without specific preparation for evaluation. All patients had MR imaging under general anesthesia. Nerve root avulsion-retraction, pseudomeningocele, and periscalene soft tissue were accepted brachial plexus injury findings on imaging. Interobserver agreement for MR imaging and the agreement between imaging and surgical findings were estimated using the κ statistic. The diagnostic accuracy of sonography and MR imaging was calculated on the basis of the standard reference, which was the surgical findings.ResultsForty-three patients had pre- and postganglionic injury, 12 had only postganglionic injury findings, and 47% of patients underwent an operation. On sonography, no patients had preganglionic injury, but all patients had postganglionic injury findings. For postganglionic injury, the concordance rates between imaging and the surgical findings ranged from 84% to 100%, and the diagnostic accuracy of sonography and MR imaging was 89% and 100%, respectively. For preganglionic injury, the diagnostic accuracy of MR imaging was 92%. Interobserver agreement and the agreement between imaging and the surgical findings were almost perfect for postganglionic injury (κ = 0.81-1, P < .001).ConclusionsHigh-resolution sonography can identify and locate the postganglionic injury associated with the upper and middle trunks. The ability of sonography to evaluate pre- and the postganglionic injury associated with the lower trunk was quite limited. Sonography can be used as a complement to MR imaging; thus, the duration of the MR imaging examination and the need for sedation can be reduced by sonography.
| S-EPMC7655297 | biostudies-literature
Project description:The anterior cingulate cortex (ACC) is thought to be important for acute pain perception as well as the development of chronic pain after peripheral nerve injury. Nevertheless, how ACC neurons respond to sensory stimulation under chronic pain states is not well understood. Here, we used an in vivo two-photon imaging technique to monitor the activity of individual neurons in the ACC of awake, head restrained mice. Calcium imaging in the dorsal ACC revealed robust somatic activity in layer 5 (L5) pyramidal neurons in response to peripheral noxious stimuli, and the degree of evoked activity was correlated with the intensity of noxious stimulation. Furthermore, the activation of ACC neurons occurred bilaterally upon noxious stimulation to either contralateral or ipsilateral hind paws. Notably, with nerve injury-induced neuropathic pain in one limb, L5 pyramidal neurons in both sides of the ACC showed enhanced activity in the absence or presence of pain stimuli. These results reveal hyperactivity of L5 pyramidal neurons in the bilateral ACC during the development of neuropathic pain.
| S-EPMC5919951 | biostudies-literature
Project description:Adult brachial plexus root avulsion can cause serious damage to nerve tissue and impair axonal regeneration, making the recovery of nerve function difficult. Nogo-A extracellular peptide residues 1-40 (NEP1-40) promote axonal regeneration by inhibiting the Nogo-66 receptor (NgR1), and poly (D, L-lactide-co-glycolide)-poly (ethylene glycol)-poly (D, L-lactide-co-glycolide) (PLGA-PEG-PLGA) hydrogel can be used to fill in tissue defects and concurrently function to sustain the release of NEP1-40. In this study, we established an adult rat model of brachial plexus nerve root avulsion injury and conducted nerve root replantation. PLGA-PEG-PLGA hydrogel combined with NEP1-40 was used to promote nerve regeneration and functional recovery in this rat model. Our results demonstrated that functional recovery was enhanced, and the survival rate of spinal anterior horn motoneurons was higher in rats that received a combination of PLGA-PEG-PLGA hydrogel and NEP1-40 than in those receiving other treatments. The combined therapy also significantly increased the number of fluorescent retrogradely labeled neurons, muscle fiber diameter, and motor endplate area of the biceps brachii. In conclusion, this study demonstrates that the effects of PLGA-PEG-PLGA hydrogel combined with NEP1-40 are superior to those of other therapies used to treat brachial plexus nerve root avulsion injury. Therefore, future studies should investigate the potential of PLGA-PEG-PLGA hydrogel as a primary treatment for brachial plexus root avulsion.
| S-EPMC8567856 | biostudies-literature