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Current literature lacks data-driven guidelines for surgical treatments of adolescents and young adults (AYAs) with chronic pelvic pain. We hypothesized that there is a significant variation in treatment of these patients, which may be an indicator of over or under treatment by some providers.
Learn More >Neuropathic pain is an unneglectable pain condition with limited treatment options owing to its enigmatic underlying mechanisms. Long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) is involved in the progression of a spectrum of human cancers. However, its role in neuropathic pain remains undiscovered. In the present study, we established a mouse spinal nerve ligation (SNL) model, and a significant upregulation of SNHG5 was observed. Then we knocked down SNHG5 level in mouse L5 dorsal root ganglion (DRG) by delivering specific short hairpin RNA against SNHG5 with adenovirus vehicle. Mouse paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in response to mechanical stimuli was increased after SNHG5 knockdown, accompanied with decreased protein levels of glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule 1 (IBA-1). Besides, SNHG5 directly modulated the expression of miR-154-5p, which was downregulated in SNL mice. MiR-154-5p inhibition abolished the effect of SNHG5 knockdown on mouse behavioral tests and GFAP and IBA-1 levels. In addition, we validated that C-X-C motif chemokine 13 (CXCL13) was a novel downstream target of miR-154-5p, and CXCL13 level was positively related to that of SNHG5 in SNL mice. In conclusion, our study demonstrated that SNHG5 knockdown alleviated neuropathic pain and inhibited the activation of astrocytes and microglia by targeting the miR-154-5p/CXCL13 axis, which might be a novel therapeutic target for neuropathic treatment clinically.
Learn More >Although the anterior cingulate cortex (ACC) plays a vital role in neuropathic pain-related aversion, the underlying mechanisms haven't been fully studied. The mesolimbic dopamine system encodes reward and aversion, and participates in the exacerbation of chronic pain. Therefore, we investigated whether the ACC modulates aversion to neuropathic pain via control of the mesolimbic dopamine system, in a rat model of chronic constriction injury (CCI) to the sciatic nerve. Using anterograde and retrograde tracings, we confirmed that a subgroup of ACC neurons projected to the nucleus accumbens (NAc) and ventral tegmental area (VTA), which are two crucial nodes of the mesolimbic dopamine system. Combining electrophysiology in juvenile rats 7 days post-CCI, we found that the NAc/VTA-projecting neurons were hyperexcitable after CCI. Chemogenetic inhibition of these projections induced conditioned place preference in young adult rats 10-14 days post-CCI, without modulating the evoked pain threshold, whereas activation of these projections in sham rats mimicked aversive behavior. Furthermore, the function of the ACC projections was probably mediated by NAc D2-type medium spiny neurons and VTA GABAergic neurons. Taken together, our findings suggest that projections from the ACC to the NAc and VTA mediate neuropathic pain-related aversive behavior.
Learn More >The goal of this study in anesthetized cats was to identify silent hypogastric nerve (HGN) afferent fibers that do not respond to bladder distention but become responsive after chemical irritation of the bladder. The HGN was split into multiple filaments small enough for recording action potentials from single or multiple afferent fibers. The bladder was distended by infusion of either saline or 0.5% acetic acid (AA) through a urethral catheter while recording intravesical pressure. A total of 90 HGN filaments from 17 cats responded to bladder distention with saline or AA. Three types of HGN afferents were identified. The first type was non-nociceptive mechano-sensitive that responded to bladder distention at normal physiological pressures (10-40 cmHO). The second type was nociceptive mechano-sensitive that only responded to high-pressure (50-80 cmHO) bladder distention with saline but responded to low-pressure bladder distention after sensitization with AA. The third type was chemo-sensitive nociceptive that was silent even during high-pressure bladder distention but after sensitization with AA did respond to low-pressure bladder distention. These results indicate that HGN afferents as well as pelvic nerve afferents may play a role in bladder nociception. The HGN afferent fibers that are silent during bladder distention at normal physiological pressures but become responsive after chemical irritation are important for understanding the possible pathophysiological mechanism underlying bladder allodynia in painful bladder syndrome.
Learn More >Migraine is the second leading cause of years lived with disability after back pain. Poor tolerability, contraindications, drug-drug interactions and efficacy limited to a subpopulation make new approaches necessary for the acute and preventive treatment of migraine. The study of the calcitonin-gene-related peptide (CGRP) pathway over the last decades is a good example of translational medicine leading to directed therapies for patients.
Learn More >Background and aims A multimodal rehabilitation programme (MMRP) is an evidence-based treatment of chronic pain conditions. The complexity involved in chronic pain needs to be identified and evaluated in order to adapt the rehabilitation to patients' needs. The aim was to investigate the multivariate relationships between self-reported variables in patients with chronic pain before taking part in MMRP in primary care, with a special focus on gender and degree of sick leave. Methods Prior to MMRP, 397 patients (339 women and 58 men) filled in a questionnaire about pain, healthcare aspects, health-related quality of life, anxiety and depression, coping, physical function, and work-related variables e.g. sick leave. Data were analysed by principal component analysis (PCA) and partial least square analysis. Results The PCA identified four components that explained 47% of the variation in the investigated data set. The first component showed the largest variation and was primarily explained by anxiety and depression, quality of life, acceptance (activity engagement), and pain-related disability. Gender differences were only seen in one component with the pain variables having the highest loadings. Degree of sick leave was not well explained by the variables in the questionnaire. Conclusions The questionnaire filled out by the patients prior to participation in MMRP in primary care identified much of the complexity of chronic pain conditions but there is room for improvement, e.g. regarding explanation of work-related factors. In the multivariate analysis, gender did not fall out as an important factor for how most patients answered the questions. Implications There are not many studies that describe patients who undergo MMRP in primary care since previously such patients were treated mostly in specialist care. More knowledge is needed about these patients in order to improve rehabilitation plans and interventions. The results suggest that the questionnaire identifies the complexity among chronic pain patients in primary care. The identified components could improve assessment before MMRP and contribute to better tailored programmes.
Learn More >The past two decades have witnessed a surge in the use of lumbar facet blocks and radiofrequency ablation (RFA) to treat low back pain (LBP), yet nearly all aspects of the procedures remain controversial.
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