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Exposure (EXP) is a cognitive-behavioral treatment aimed at reducing pain-related fear in chronic pain, and has proven successful in reducing pain-related disability in patients with chronic low back pain (cLBP). The current longitudinal study aimed to reveal the neural correlates of changes in pain-related fear as a result of EXP. Twenty-three patients with cLBP were included in this study. Patients with cLBP underwent MRI scanning pre-treatment (pre-EXP), post-treatment (post-EXP), and 6 months after end of treatment (FU-EXP). Pain-free controls were scanned at two time points. In the scanner, participants were presented with pictures involving back-related movements, evoking pain-related fear in patients. Pre-treatment, functional MRI revealed increased activation in right posterior insula and increased deactivation in medial prefrontal cortex (mPFC) in patients compared to controls. Post-treatment, patients reported reduced fear and pre-EXP group differences were no longer present. Contrasting pre- to post- and FU-EXP in patients revealed that stimulus-evoked neural responses changed in sensorimotor as well as cognitive/affective brain regions. Lastly, exploratory analyses revealed a tendency toward an association between changes in neural activation and changes in fear ratings, including the hippocampus and temporal lobe (pre- to post-EXP changes), and mPFC and posterior cingulate cortex (pre- to FU-EXP changes). Taken together, we show evidence that neural circuitry for pain-related fear is modulated by EXP, and that changes are associated with self-reported decreases in pain-related fear.
Learn More >Chronic pain is associated with decreased quality of life and is one of the most common reasons adults seek medical care, making treatment imperative for many aspects of patient well-being. Chronic pain management typically involves the use of Schedule II full μ-opioid receptor agonists for pain relief; however, the increasing prevalence of opioid addiction is a national crisis that is impacting public health and social and economic welfare. Buprenorphine is a Schedule III partial μ-opioid receptor agonist that is an equally effective but potentially safer treatment option for chronic pain than full μ-opioid receptor agonists. The purpose of this review is to provide an overview of the clinical efficacy and safety of the transdermal and buccal formulations of buprenorphine, which are approved by the Food and Drug Administration for chronic pain, compared with that of extended-release full μ-opioid receptor agonists.
Learn More >A key concern for people with chronic pain is experiencing increased pain and/or re-injury. Consequently, individuals with chronic pain can develop a maladaptive fear of movement that leads to adverse functional consequences. A primary goal of chronic pain rehabilitation is re-engagement in feared movements through exposure. This is often challenging since safe movement can be uncomfortable. Virtual environments provide a promising opportunity to safely and gradually expose Veterans to movements that are avoided in the real world. The current study will utilize multiple virtual reality (VR) applications (APPs) of varying the intensity levels ranging from passive distraction from pain to active exposure to feared movement. The primary aims of this pilot are to examine VR as an adjunctive nonpharmacological intervention to assist with the adoption and implementation of skills to decrease fear of movement and increase overall functioning among Veterans with chronic pain. Second, to build a hierarchy of VR APPs to assist in gradual exposure to feared movements.
Learn More >Chronic low back pain (cLBP) is associated with widespread functional and structural changes in the brain. This study aims to investigate the resting state functional connectivity (rsFC) changes of visual networks in cLBP patients and the feasibility of distinguishing cLBP patients from healthy controls using machine learning methods. cLBP (n = 90) and control individuals (n = 74) were enrolled and underwent resting-state BOLD fMRI scans. Primary, dorsal, and ventral visual networks derived from independent component analysis were used as regions of interest to compare resting state functional connectivity changes between the cLBP patients and healthy controls. We then applied a support vector machine classifier to distinguish the cLBP patients and control individuals. These results were further verified in a new cohort of subjects. We found that the functional connectivity between the primary visual network and the somatosensory/motor areas were significantly enhanced in cLBP patients. The rsFC between the primary visual network and S1 was negatively associated with duration of cLBP. In addition, we found that the rsFC of the visual network could achieve a classification accuracy of 79.3% in distinguishing cLBP patients from HCs, and these results were further validated in an independent cohort of subjects (accuracy = 66.7%). Our results demonstrate significant changes in the rsFC of the visual networks in cLBP patients. We speculate these alterations may represent an adaptation/self-adjustment mechanism and cross-model interaction between the visual, somatosensory, motor, attention, and salient networks in response to cLBP. Elucidating the role of the visual networks in cLBP may shed light on the pathophysiology and development of the disorder.
Learn More >Neuropathic pain (NP) is among the most intractable comorbidities of spinal cord injury. Dysregulation of non-coding RNAs has also been implicated in the development of neuropathic pain. Here, we identified a novel lncRNA, PKIA-AS1, by using lncRNA array analysis in spinal cord tissue of spinal nerve ligation (SNL) model rats, and investigated the role of PKIA-AS1 in SNL-mediated neuropathic pain. We observed that PKIA-AS1 was significantly upregulated in SNL model rats and that PKIA-AS1 knockdown attenuated neuropathic pain progression. Alternatively, overexpression of PKIA-AS1 was sufficient to induce neuropathic pain-like symptoms in uninjured rats. We also found that PKIA-AS1 mediated SNL-induced neuropathic pain by directly regulating the expression and function of CDK6, which is essential for the initiation and maintenance of neuroinflammation and neuropathic pain. Therefore, our study identifies PKIA-AS1 as a novel therapeutic target for neuroinflammation related neuropathic pain.
Learn More >Sedation and somnolence remain serious adverse effects of the existing analgesics (e.g., pregabalin, duloxetine) for neuropathic pain. The available evidence indicates that serotonin (5-HT), noradrenaline (NE), and dopamine (DA) play important roles in modulating the descending inhibitory pain pathway and sleep-wake cycle. The aim of this work was to test the hypothesis that LPM580098, a novel triple reuptake inhibitor (TRI) of 5-HT, NE, and DA, has analgesic effect, and does not induce significant adverse effects associated with central inhibition, such as sedation and somnolence. The analgesic activity of LPM580098 was assessed on formalin test and spinal nerve ligation (SNL)-induced neuropathic pain model. Locomotor activity, pentobarbital sodium-induced sleeping and rota-rod tests were also conducted. binding and uptake assays, and Western blotting were performed to examine the potential mechanisms. LPM580098 suppressed the nocifensive behaviors during phase II of the formalin test in mice. In SNL rats, LPM580098 (16 mg kg) inhibited mechanical allodynia, thermal hyperalgesia and hyperexcitation of wide-dynamic range (WDR) neurons, in which the effect of LPM580098 was similar to pregabalin (30 mg kg). However, pregabalin altered the spontaneous locomotion, affected pentobarbital sodium-induced sleep, and showed a trend to perform motor dysfunction, which were not induced by LPM580098. Mechanistically, LPM580098 inhibited the uptake of 5-HT, NE, and DA, improved pain-induced changes of the synaptic functional plasticity and structural plasticity possibly via downregulating the NR2B/CaMKIIα/GluR1 and Rac1/RhoA signaling pathways. Our results suggest that LPM580098, a novel TRI, is effective in attenuating neuropathic pain without producing unwanted sedation and somnolence associated with central nervous system (CNS) depressants.
Learn More >In the central nervous system (CNS), astrocytes form networks interconnected by gap junctions made from connexins of the subtypes Cx30 and Cx43. When unopposed by an adjoining hemichannel, astrocytic connexins can act as hemichannels to control the release of small molecules such as ATP and glutamate into the extracellular space. Accruing evidence indicates that astrocytic connexins are crucial for the coordination and maintenance of physiologic CNS activity. Here we provide an update on the role of astrocytic connexins in neurodegenerative disorders, glioma, and ischemia. In addition, we address the regulation of Cx43 in chronic pain.
Learn More >Regenerative medicine is a medical subspecialty that seeks to recruit and enhance the body's own inherent healing armamentarium in the treatment of patient pathology. This therapy's intention is to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous or allogenic biologics. This field is rising like a Phoenix from the ashes of underperforming conventional therapy midst the hopes and high expectations of patients and medical personnel alike. But, because this is a relatively new area of medicine that has yet to substantiate its outcomes, care must be taken in its public presentation and promises as well as in its use.
Learn More >The aim of this study was to identify the clinical characteristics, treatment usage, and health outcomes of US adults diagnosed with neuropathic pain (NeP) by experienced physicians.
Learn More >Increasing evidence purports exercise as a first-line therapeutic for the treatment of nearly all forms of chronic pain. However, knowledge of efficacious dosing respective to treatment modality and pain condition is virtually absent in the literature. The purpose of this analysis was to calculate the extent to which exercise treatment shows dose-dependent effects similar to what is seen with pharmacological treatments.
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