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Neuropathic pain (NP) is caused by primary or secondary impairment of the peripheral or central nervous systems. Its etiology is complex and involves abnormal patterns of gene expression and pathway activation. Using bioinformatics analysis, we aimed to identify NP-associated changes in genes and pathways in L4 and L5 dorsal root ganglia (DRG) in a rat model of NP induced by chronic compression of the DRG (CCD). Genome-wide transcriptional analyses were used to elucidate the molecular mechanisms underlying NP. We screened differentially expressed genes (DEGs) 7 days after CCD in comparison with sham-operated controls. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to confirm the presence of key DEGs. Kyoto Encyclopedia of Genes and Genomes (KEGG)-pathway analysis of DEGs and global signal transduction network analysis of DEGs were also conducted. The CCD group developed clear mechanical and thermal allodynia in the ipsilateral hind paw compared with the sham group. This comparison identified 1,887 DEGs, with 1156 upregulated and 731 downregulated DEGs, and 123 DEG-enriched pathways. We identified the key candidate genes that might play a role in the development of NP, namely (), , (), (), (), and () by analyzing the global signal transduction network. RT-qPCR and western blot analysis confirmed the microarray results. The DEGs , , , , and , and the cytokine signaling pathway, the neuroactive ligand-receptor interaction, the toll-like receptor signaling pathway, and the PI3K-Akt signaling pathway may have decisive modulatory roles in both nerve regeneration and NP. These results provide deeper insight into the mechanism underlying NP and promising therapeutic targets for its treatment.
Complex Regional Pain Syndrome (CRPS) is a poorly understood chronic pain condition of multifactorial origin. CRPS involves sensory, motor, and autonomic symptoms primarily affecting one extremity. Patients can also present with neuropsychological changes such as reduced attention to the CRPS-affected extremity, reminiscent of hemispatial neglect, yet in the absence of any brain lesions. However, this "neglect-like" framework is not sufficient to characterise the range of higher cognitive functions that can be altered in CRPS. This comprehensive literature review synthesises evidence of neuropsychological changes in CRPS in the context of potential central mechanisms of the disorder. The affected neuropsychological functions constitute three distinct but not independent groups: distorted body representation, deficits in lateralised spatial cognition, and impairment of non-spatially-lateralised higher cognitive functions. We suggest that many of these symptoms appear to be consistent with a broader disruption to parietal function beyond merely what could be considered "neglect-like." Moreover, the extent of neuropsychological symptoms might be related to the clinical signs of CRPS, and rehabilitation methods that target the neuropsychological changes can improve clinical outcomes in CRPS and other chronic pain conditions. Based on the limitations and gaps in the reviewed literature, we provide several suggestions to improve further research on neuropsychological changes in chronic pain.
In this chapter, we describe the impact and etiology of chronic pain, the associated changes in the nervous system, and the mechanisms by which exercise may be able to affect and reverse these changes. Evidence for efficacy of exercise in different conditions associated with chronic pain is presented, with focus on chronic low back pain, fibromyalgia, osteoarthritis, rheumatoid arthritis, and migraines. While the efficacy of exercise and level of evidence supporting it vary in different diseases, exercise has direct and indirect benefits for most patients suffering from chronic pain. Effective exercise regimens include education and cognitive restructuring to promote behavioral activation and reconceptualization of what pain means, with the goal of gradually reversing the vicious cycle of pain, inertia, sedentary behavior, and worsening disability. Long-term, consistent, individualized exercise-based treatment approaches are most likely to result in improvements in pain and function.
To report the theoretical basis and design of a novel digital Acceptance and Commitment Therapy (ACT) intervention for people with chronic pain, the Pain Tracker Self Manager (PTSM), which had promising efficacy in a recent pilot trial.
Switching microglial polarization from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype represents a novel therapeutic strategy for neuropathic pain (NP). This study aims to investigate whether botulinum toxin type A (BTX-A) regulates microglial M1/M2 polarization by inhibiting P2X7 expression in a rat model of NP.
Recent task-based fMRI studies have shown that Persistent Somatoform Pain Disorder (PSPD) patients demonstrated aberrant activity in a wide range of brain regions associated with sensation, cognition and emotion. However, these specific task-based studies could not clearly uncover the alterations in the spontaneous brain networks that were associated with the general pain-related symptoms in PSPD.
G protein-gated inwardly rectifying potassium (GIRK) channels are involved in the regulation of neuronal excitability. Four GIRK subunits (GIRK1-4) are expressed in rat dorsal root ganglia (DRGs). Recently, we have characterized the expression of GIRK1 and -2, and both are downregulated in rat DRGs and spinal cord after a complete sciatic nerve transection (axotomy). Here, we aimed to study the neurochemical characteristics of GIRK3, and its regulation in rat DRGs and spinal cord induced by nerve injury.
There is a need for reliable and valid clinical assessment tools for quantifying allodynia in neuropathic pain. Allodynography has been proposed as a useful standardized procedure for clinical assessment of mechanical allodynia. This study (www.clinicaltrials.gov NCT02070367) undertook preliminary investigation of the measurement properties of allodynography, a new standardized clinical examination procedure for mapping the area of cutaneous allodynia.
To investigate the effect of phase polarity and charge balance of spinal cord stimulation (SCS) waveforms on pain behavior and gene expression in a neuropathic pain rodent model. We hypothesized that differing waveforms will result in diverse behavioral and transcriptomics expression due to unique mechanisms of action.
To investigate the association of migraine genetic variants with cerebral blood flow (CBF).