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To investigate whether illness perceptions, measured with the Brief Illness Perception Questionnaire, are an independent predictor of chronic low back pain and pain-related disability at 12 weeks.
Learn More >We tested whether aerobic exercise training altered morphine analgesic responses or reduced morphine dosages necessary for adequate analgesia. Chronic back pain patients were randomized to an 18-session aerobic exercise intervention (n = 38) or usual activity control (n = 45). Before and after the intervention, participants underwent three laboratory sessions (double-blinded, crossover) to assess effects of saline placebo, i.v. morphine (0.09 mg/kg), and i.v. naloxone (12 mg) on low back pain and evoked heat pain responses. Differences in evoked and back pain measures between the placebo and morphine conditions indexed morphine analgesia, with pre-post intervention changes the primary outcome. Endogenous opioid (EO) analgesia was indexed by differences in evoked and low back pain measures between the naloxone and placebo conditions. A Sex X Intervention interaction on the analgesic effects of morphine on VAS back pain intensity was observed (p = .046), with a similar trend for evoked pain threshold (p = .093). Male exercisers showed reduced morphine analgesia pre-post intervention whereas male controls showed increased analgesia (with no differences in females). Of clinical significance were findings that relative to the control group, aerobic exercise produced analgesia more similar to that observed after receiving ≈7 mg morphine pre-intervention (p's < .045). Greater pre-post intervention increases in EO function (from any source) were significantly associated with larger pre-post intervention decreases in morphine analgesia (p's < .046). The overall pattern of findings suggest that regular aerobic exercise has limited direct effects on morphine responsiveness, reducing morphine analgesia in males only.
Learn More >Conditioned pain modulation (CPM) is a centrally processed measure of the net effect of the descending pain pathway. This comprises both the facilitatory as well as the inhibitory effect. In the past, CPM or similar effects have been previously described using different terminologies such as diffuse noxious inhibitory control (DNIC), heterotopic noxious conditioning stimulation (HNCS) or endogenous analgesia (EA). A variety of patient-related factors such as age, gender, hormones, race, genetic and psychological factors have been thought to influence the CPM paradigms. CPM paradigms have also been associated with a wide range of methodological variables including the mode of application of the 'test' as well as the 'conditioning' stimuli. Despite all these variabilities, CPM seems to reliably lend itself to the pain modulation profile concept and could in future become one of the phenotypic biomarkers for pain and also a guide for mechanism-based treatment in chronic pain. Future research should focus on establishing consistent methodologies for measuring CPM and thereby enhancing the robustness of this emerging biomarker for pain.
Learn More >Brief psychological interventions (BPIs) have demonstrated effectiveness in reducing substance use and related harm. No systematic review has examined their potential to reduce or prevent prescription opioid use or related harm, and/or pain intensity in opioid-using patients with chronic non-cancer pain (CNCP). Recognizing the importance of patient preferences in evidence-based practice, we also sought to assess patient interest in BPIs.
Learn More >In this study of 154 community-dwelling older adults with chronic non-cancer pain, we sought to assess participants' beliefs about pain as well as pain management treatments and determined the influence of those beliefs on participants' willingness to undertake three physician-recommended pain treatments, i.e., a pharmacologic, physical, and psychological therapy.
Learn More >There has been a long-standing debate regarding the role of peripheral afferents in mediating rapid-onset anorexia among other responses elicited by peripheral inflammatory insults. Thus, the current study assessed the sufficiency of peripheral afferents expressing toll-like receptor 4 (TLR4) to the initiation of the anorexia caused by peripheral bacterial lipopolysaccharide (LPS). We generated a Tlr4 null (Tlr4) mouse in which Tlr4 expression is globally disrupted by a loxP-flanked transcription blocking cassette. This novel mouse model allowed us to restore the endogenous TLR4 expression in specific cell types. Using Zp3-Cre and Na1.8-Cre mice, we produced mice that express TLR4 in all cells (Tlr4 X Zp3-Cre) and in peripheral afferents (Tlr4 X Na1.8-Cre), respectively. We validated the Tlr4 mice, which were phenotypically identical to previously reported global TLR4 knock-out mice. Contrary to our expectations, the administration of LPS did not cause rapid-onset anorexia in mice with Na1.8-restricted TLR4. The later result prompted us to identify Tlr4-expressing vagal afferents using hybridization. , we found that Tlr4 mRNA was primarily enriched in vagal Na1.8 afferents located in the jugular ganglion that co-expressed Calcitonin gene-related peptide (CGRP). , the application of LPS to cultured Na1.8-restricted TLR4 afferents was sufficient to stimulate the release and expression of CGRP. In summary, we demonstrated using a new mouse model that vagally-expressed TLR4 is selectively involved in stimulating the release of CGRP, but not in causing anorexia. Using a new transgenic mouse model, our data establish that TLR4 is both sufficient and required for the release of CGRP from a subset of vagal afferents. This finding may be relevant to the understanding of how bacterial infections modulate nerves.
Learn More >Engineered human mini-brains, made possible by knowledge from the convergence of precision microengineering and cell biology, permit systematic studies of complex neurological processes and of pathogenesis beyond what can be done with animal models. By culturing human brain cells with physiological microenvironmental cues, human mini-brain models reconstitute the arrangement of structural tissues and some of the complex biological functions of the human brain. In this Review, we highlight the most significant developments that have led to microphysiological human mini-brain models. We introduce the history of mini-brain development, review methods for creating mini-brain models in static conditions, and discuss relevant state-of-the-art dynamic cell-culture systems. We also review human mini-brain models that reconstruct aspects of major neurological disorders under static or dynamic conditions. Engineered human mini-brains will contribute to advancing the study of the physiology and aetiology of neurological disorders, and to the development of personalized medicines for them.
Learn More >The risk constructs based on psychological risk factors (e.g. pain catastrophizing, PC) and sensitization risk factors (e.g. pressure pain threshold, PPT) are important in research and clinical practice. While most research looks at individual constructs, but doesn't consider how different constructs might interact within the same individual. A cumulative impact evaluation of psychological and sensitization risk factors on pain-related outcomes may help guide us in the risk assessment of patients with pain conditions. The aim of this study is to evaluate the cumulative impact of these psychological PC and sensitization PPT risk factors on pain-related outcomes (activity avoidance, pain severity and disability) considering covariates.
Learn More >The voltage-gated sodium channel Na1.8 mediates the tetrodotoxin-resistant (TTX-R) Na current in nociceptive primary sensory neurons, which has an important role in the transmission of painful stimuli. Here, we describe the functional modulation of the human Na1.8 α-subunit in oocytes by auxiliary β subunits. We found that the β3 subunit down-regulated the maximal Na current amplitude and decelerated recovery from inactivation of hNa1.8, whereas the β1 and β2 subunits had no such effects. The specific regulation of Na1.8 by the β3 subunit constitutes a potential novel regulatory mechanism of the TTX-R Na current in primary sensory neurons with potential implications in chronic pain states. In particular, neuropathic pain states are characterised by a down-regulation of Na1.8 accompanied by increased expression of the β3 subunit. Our results suggest that these two phenomena may be correlated, and that increased levels of the β3 subunit may directly contribute to the down-regulation of Na1.8. To determine which domain of the β3 subunit is responsible for the specific regulation of hNa1.8, we created chimeras of the β1 and β3 subunits and co-expressed them with the hNa1.8 α-subunit in oocytes. The intracellular domain of the β3 subunit was shown to be responsible for the down-regulation of maximal Na1.8 current amplitudes. In contrast, the extracellular domain mediated the effect of the β3 subunit on hNa1.8 recovery kinetics.
Learn More >In this study, we investigated the relationship between sensory abnormalities evaluated by quantitative sensory testing (QST) and alexithymia, depression and anxiety in patients with neuropathic pain involving the upper limbs. We enrolled 62 patients (34 with carpal tunnel syndrome, 7 with brachial plexopathy, 3 with cervical painful radiculopathy, 5 with ulnar entrapment neuropathy at elbow and 13 with post-burn hypertrophic scars) and 48 healthy controls. All underwent nerve conduction studies (NCS), evaluation of cold, heat pain and vibration detection threshold (VDT) by QST and evaluation of alexithymia by Toronto Alexithymia Scale (TAS-20), depression by Beck Depression Inventory II (BDI-II), anxiety by State-Trait Anxiety Inventory (STAI-Y), level of psychological distress by 12-item General Health Questionnaire (GHQ-12) and perceived social support by the Multidimensional Scale of Perceived Social Support (MSPSS). The general linear model analysis revealed a significant relationship between TAS-20 overall and TAS-20 sub-score for difficulty identifying feelings and VDT z-scores in the left index with no interaction by year of education and sensory NCS results. Our results demonstrated the association between impairment of vibratory sensation of the left hand, reflecting cutaneous mechanoceptor dysfunction, and alexithymia, particularly the difficulty to identify feelings. The importance of delivering to patients with neuropathic pain personalized care that takes into account not only the neurophysiological aspects but also the aspects of mental functioning is discussed.
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