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The current study aimed to identify alterations in brain activation and connectivity related to nociceptive processing and pain sensitization in major depressive disorder (MDD), using repetitive heat pain stimulation during functional magnetic resonance imaging (fMRI) in 37 MDD patients and 33 healthy controls. Regional activation did not differ between groups, but functional connectivity was significantly decreased in MDD in a neural network connecting frontal, temporal and occipital areas (family-wise error-corrected p = 0.045). Supporting analyses suggested a significant association between network connectivity and trait neuroticism (p = 0.007) but not with the clinical state or familiar risk of MDD (all p values > 0.13). Our data relate a network-based phenotype for altered pain processing and antinociceptive control to MDD and encourage future studies on the shared intermediate neural psychological risk architecture of MDD and chronic pain.
Learn More >Multimodal analgesia (MMA) is the simultaneous use of multiple analgesic medications that work in a synergistic manner to provide pain control. In recent years, spine surgery has seen the growth of multimodal perioperative protocols for managing pain. Postoperative pain following spinal procedures is a common complaint, with persistent pain even after the immediate convalescent period leading to negative impacts on health. A multidisciplinary approach is essential in reducing postoperative morbidity and complication rates. This review demonstrates the efficacy in the combined use of opioid-alternative medications such as NSAIDs, gabapentinoids, local anesthetics, acetaminophen, and other neuromodulatory pharmacologic agents. Continued research will be essential in the optimization of the MMA protocol for treating patients who undergo spine procedures.
Learn More >A growing body of evidence suggests that chronic pain is associated with perceptual changes, such as impaired tactile acuity and laterality judgements. A recent study on low back pain showed that tactile acuity was reduced immediately after acute pain induction. Biologically, acute pain should lead to enhanced rather than disruptive changes in tactile acuity to meaningfully respond to potentially damaging nociceptive stimuli. In this double-blinded experiment, 30 healthy volunteers attended three experimental sessions (injection, sham-injection and control condition) separated by one week each, to investigate the effect of acute nociception on tactile precision and laterality judgements. In the real injection condition, acute pain was induced by hypertonic saline solution injected into the mid portion of the trapezius muscle. Tactile acuity (two-point discrimination and an estimation task) and laterality judgements were measured before and during pain perception. In the sham condition the injection was mimicked by a sham procedure (without piercing the skin), in the control condition no intervention took place. Results showed that tactile acuity remained intact (P=0.92) indicating that experimentally induced neck pain did not affect tactile precision. The time needed to complete the laterality judgement task improved over-time in all conditions reflecting a learning effect (P=0.05), We conclude that acute neck pain does not result in perceptual distortions, possibly reflecting a higher protection demand for the neck, a body region in close anatomical proximity to neural centers responsible for vital functions. This data -in the context of existing evidence- indicates that tactile acuity may respond differently to noxious stimulation in different anatomical regions. Perspective: In this study, a sensory adaptation to acute neck pain was investigated. It was found that experimental neck pain did not elicit changes in the sensory axis leaving tactile acuity intact in otherwise healthy subjects. These data support site-specific sensory adaptation to pain.
Learn More >Intrathecal treatment with recombinant high-mobility group box-1 (rHMGB1) in naïve mice leads to a persistent and significantly decreased hind paw withdrawal threshold to mechanical stimuli, suggesting that spinal HMGB1 evokes abnormal pain processing. By contrast, repeated intrathecal treatment with anti-HMGB1 antibody significantly reverses hind paw mechano-hypersensitivity in mice with a partial sciatic nerve ligation (PSNL). By contrast, the cellular mechanism by which spinal HMGB1 induces neuropathic pain has yet to be fully elaborated. The current study tested the hypothesis that spinal HMGB1 could induce mechanical hypersensitivity through the activation of specific receptor in glial cells. Intrathecal pretreatment with toll-like receptor (TLR) 4 inhibitors, but not TLR5, receptor for advanced glycation end-products and C-X-C chemokine receptor type 4 inhibitors, prevented rHMGB1-evoked mechanical hypersensitivity. Activation of spinal astrocytes appears to be crucial for the mechanism of action of rHMGB1 in naïve mice, as intrathecal pretreatment with astrocytic inhibitors prevented the rHMGB1-induced mechanical hypersensitivity. Within activated astrocytes, interleukin-1β (IL-1β) was up-regulated, which was prevented with blockade of TLR4. Interleukin-1β appears to be secreted by activated astrocytes, as IL-1β neutralizing antibody prevented rHMGB1-induced mechanical hypersensitivity. Furthermore, intrathecal pretreatment with either MK801 or gabapentin prevented the rHMGB1-induced mechanical hypersensitivity, suggesting roles for spinal glutamate and the N-methyl-D-aspartate receptor in the mediation of rHMGB1-induced mechanical hypersensitivity. Thus, the current findings suggest that spinal HMGB1 upregulates IL-1β in spinal astrocytes through a TLR4-dependent pathway and increases glutamatergic nociceptive transduction. These spinal mechanisms could be key steps that maintain neuropathic pain. This article is protected by copyright. All rights reserved.
Learn More >Chronic musculoskeletal pain is often accompanied by depression or anxiety wherein co-occurring pain and mood symptoms can be more difficult to treat than either alone. However, few clinical trials have examined interventions that simultaneously target both pain and mood conditions.
Learn More >The primary aim of this exploratory study was to assess the relationship between anxiety sensitivity and emotional disorders, migraine characteristics, and migraine-related fear and avoidance behaviors in women with probable migraine.
Learn More >Pain is a frequent and disabling symptom in multiple sclerosis (MS) patients; however, the underlying mechanisms of MS-related pain is not fully understood. Here, we demonstrated that cathepsin E (CatE) in neutrophils contributes to the generation of mechanical allodynia in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. We showed that CatE-deficient (CatE) mice were highly resistant to myelin oligodendrocyte glycoprotein (MOG35-55)-induced mechanical allodynia. After MOG35-55 immunization, neutrophils immediately accumulated in the dorsal root ganglion (DRG). Adoptive transfer of MOG35-55-stimulated wild-type neutrophils into the DRG induced mechanical allodynia in the recipient C57BL/6 mice. On the other hand, the pain threshold did not change when MOG35-55-stimulated CatE neutrophils were transferred into the recipient C57BL/6 mice. MOG35-55 stimulation caused CatE-dependent secretion of elastase in neutrophils. Behavioral analyses revealed that sivelestat, a selective neutrophil elastase inhibitor, suppressed mechanical allodynia induced by adoptively transferred MOG35-55-stimulated neutrophils. MOG35-55 directly bound to toll-like receptor 4, which led to increased production of CatE in neutrophils. Our findings suggest that inhibition of CatE-dependent elastase production in neutrophil might be a potential therapeutic target for pain in MS patients.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Learn More >Hypersensitivity due to central pain mechanisms can influence recovery and lead to worse clinical outcomes, but the ability of quantitative sensory testing (QST), an index of sensitisation, to predict outcomes in chronic musculoskeletal disorders remains unclear. We systematically reviewed the evidence for ability of QST to predict pain, disability and negative affect using searches of CENTRAL, MEDLINE, EMBASE, AMED, CINAHL and PubMed databases up to April 2018. Title screening, data extraction, and methodological quality assessments were performed independently by 2 reviewers. Associations were reported between baseline QST and outcomes using adjusted (β) and unadjusted (r) correlations. Of the 37 eligible studies (n=3860 participants), 32 were prospective cohort studies and 5 randomised controlled trials. Pain was an outcome in 30 studies, disability in 11 and negative affect in 3. Meta-analysis revealed that baseline QST predicted musculoskeletal pain (mean r=0.31, 95%CI: 0.23 to 0.38, n=1057 participants) and disability (mean r=0.30, 95%CI: 0.19 to 0.40, n=290 participants). Baseline modalities quantifying central mechanisms such as temporal summation (TS) and conditioned pain modulation (CPM) were associated with follow-up pain (TS: mean r=0.37, 95%CI: 0.17 to 0.54; CPM: r=0.36, 95%CI: 0.20 to 0.50), whereas baseline mechanical threshold modalities were predictive of follow-up disability (mean r=0.25, 95%CI: 0.03 to 0.45). QST indices of pain hypersensitivity might help develop targeted interventions aiming to improve outcomes across a range of musculoskeletal conditions.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) , where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.
Learn More >To provide updated evidence-based recommendations for migraine prevention using pharmacologic treatment with or without cognitive behavioral therapy in the pediatric population.
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