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Regeneration after injury occurs in axons that lie in the peripheral nervous system but fails in the central nervous system, thereby limiting functional recovery. Differences in axonal signalling in response to injury that might underpin this differential regenerative ability are poorly characterized. Combining axoplasmic proteomics from peripheral sciatic or central projecting dorsal root ganglion (DRG) axons with cell body RNA-seq, we uncover injury-dependent signalling pathways that are uniquely represented in peripheral versus central projecting sciatic DRG axons. We identify AMPK as a crucial regulator of axonal regenerative signalling that is specifically downregulated in injured peripheral, but not central, axons. We find that AMPK in DRG interacts with the 26S proteasome and its CaMKIIα-dependent regulatory subunit PSMC5 to promote AMPKα proteasomal degradation following sciatic axotomy. Conditional deletion of AMPKα1 promotes multiple regenerative signalling pathways after central axonal injury and stimulates robust axonal growth across the spinal cord injury site, suggesting inhibition of AMPK as a therapeutic strategy to enhance regeneration following spinal cord injury.
Learn More >Chronic low back pain (cLBP) can interfere with daily activities, and individuals with elevated pain-related fear (also known as kinesiophobia or the fear of injury due to movement) can develop worse long-term disability. Graded exposure (GEXP) protocols use successive participation in avoided activities to help individuals overcome fearful movement appraisals and encourage activity. We sought to develop a series of GEXP virtual reality (VR) walking and reaching scenarios to increase the exposure and engagement of people with high kinesiophobia and cLBP.
Learn More >This study investigated relationships between post-traumatic stress symptoms (PTSS) and pain disability. Fifty people with chronic pain (probable PTSD, = 22) completed measures assessing pain interference, PTSS, fear avoidance, and pain self-efficacy. We hypothesized that people with probable PTSD would have higher fear avoidance and lower pain self-efficacy; and that PTSS would be indirectly associated with pain disability via fear avoidance and self-efficacy. People with probable PTSD had higher fear avoidance, but there were no differences in self-efficacy, pain severity or disability. There was an indirect association between PTSS and pain disability via fear avoidance, but not via self-efficacy.
Learn More >The opioid epidemic is a significant public health crisis in the United States, and chronic pain is a leading precipitating and maintaining factor for opioid misuse. To better understand substance misuse generally, research has examined motivational models of why people use substances, and pain management and affect-driven coping are cited as primary reasons for opioid misuse. Further, research examining psychosocial predictors of opioid misuse has identified anxiety sensitivity (AS; fear of anxiety-related physical sensations) as a unique predictor of opioid misuse severity, and it is possible that AS is uniquely related to opioid pain management and coping motives, which in turn, are related to opioid misuse. Therefore, the current study examined AS as a predictor of opioid pain management and coping motives, as well as the indirect effect of AS, through opioid motives, on opioid misuse status, among 292 adults (Mage = 45.76, SD = 11.20, 68.9% female) with chronic low back pain. Results for the current study support hypotheses that AS is significantly associated with pain management and coping motives (over and above variance of pain intensity) and indirectly associated with opioid misuse status through both motives. These results highlight the importance of better understanding opioid use motives in the context of chronic pain and provide potential treatment targets to add to a growing body of literature targeting psychosocial factors for opioid misuse. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
Learn More >Diabetic polyneuropathy (DPN) is a common complication of diabetes. Using the Toronto criteria for diabetic polyneuropathy and the grading system for neuropathic pain, the performance of neuropathy scales and questionnaires were assessed by comparing them to a clinical gold standard diagnosis of DPN and painful DPN in a cohort of patients with recently diagnosed type 2 diabetes.
Learn More >Epidemiological studies have shown that 6.9-10% of people suffer from neuropathic pain, a complex painful condition which is often undertreated. Data regarding the effectiveness of treatment options for patients with neuropathic pain is inconsistent, and there is no single treatment option that shows cost-effectiveness across studies.
Learn More >To evaluate the preferences of patients with osteoarthritis for treatment.
Learn More >The neuroanatomical basis behind acupuncture practice is still poorly understood. Here, we used intersectional genetic strategy to ablate NPY noradrenergic neurons and/or adrenal chromaffin cells. Using endotoxin-induced systemic inflammation as a model, we found that electroacupuncture stimulation (ES) drives sympathetic pathways in somatotopy- and intensity-dependent manners. Low-intensity ES at hindlimb regions drives the vagal-adrenal axis, producing anti-inflammatory effects that depend on NPY adrenal chromaffin cells. High-intensity ES at the abdomen activates NPY splenic noradrenergic neurons via the spinal-sympathetic axis; these neurons engage incoherent feedforward regulatory loops via activation of distinct adrenergic receptors (ARs), and their ES-evoked activation produces either anti- or pro-inflammatory effects due to disease-state-dependent changes in AR profiles. The revelation of somatotopic organization and intensity dependency in driving distinct autonomic pathways could form a road map for optimizing stimulation parameters to improve both efficacy and safety in using acupuncture as a therapeutic modality.
Learn More >The anterior cingulate cortex (ACC) is activated by noxious stimuli and is involved in the affective component of pain processing; but its role in the sensory component of pain remains largely unknown. Studies have verified that Chemokine (C-X-C motif) receptor 3 (CXCR3) is involved in nociceptive sensitization in the spinal cord after peripheral nerve injury; however, the expression of CXCR3 in the ACC and its role in neuropathic pain has not been reported. Here, we showed that CXCR3 co-localized with neurons in the ACC and the upregulation of CXCR3 corresponded with hypersensitive behaviors after a chronic constriction injury of the sciatic nerve. Pharmacological blockade of CXCR3 using local injection of its inhibitor, AMG487, into the ACC significantly attenuated hyperalgesia induced by chronic constriction injury and suppressed the phosphorylation of extracellular signal-regulated kinase (ERK). Collectively, these results suggest that CXCR3 in the ACC is involved in hyperalgesia induced by peripheral nerve injury and ERK may be a downstream target.
Learn More >This prospective study characterized corneal nerve pathway function in individuals with dry eye symptoms. In total, 34% of individuals had a corneal sensitivity outside the 10-90% range or persistent pain after placement of topical anesthesia.
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