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Properties of Thermal Analgesia in a Human Chronic Low Back Pain Model.

ABSTRACT: Purpose:For years, heat has been used for comfort and analgesia is recommended as a first-line therapy in many clinical guidelines. Yet, there are questions that remain about the actual effectiveness of heat for a condition as common as chronic low back pain, and factors such as time of onset, optimal temperature, and duration of effect. Materials and Methods:A randomized double-blinded controlled trial was designed to compare the analgesic response to heat delivered via pulses at 45°C (experimental group, N=49) to steady heat at 37°C (control group, N=51) in subjects with longstanding low back pain. Treatment lasted 30 minutes with follow-up out to four hours. The hypothesis was that the experimental group would experience a higher degree of analgesia compared to the control group. Time of onset and duration of effect were also measured. Results:Both groups were similar in average duration of pain (10.3 years). The primary outcome measure was pain reduction at 30 minutes after the end of treatment, using a 10-points numeric pain scale. Reduction in pain was greater for the experimental group than the control group (difference in mean reduction = 0.72, 95% CI 0.15-1.29, p = 0.014). Statistically significant differences in pain levels were observed from the first measure at 5 minutes of treatment through 120 minutes after completion of treatment. Reduction in pain associated movement was greater in the active heat group than the placebo group (p = 0.04). Conclusion:High-level pulsed heat (45°C) produced significantly more analgesia as compared to steady heat at 37°C at the primary end point and for an additional 2 hours after treatment. The onset of analgesia was rapid, <5 minutes of treatment. The results of this trial provide insight into the mechanisms and properties of thermal analgesia that are not well understood in a chronic low back pain model.

SUBMITTER: Chabal C

PROVIDER: S-EPMC7434528 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Properties of Thermal Analgesia in a Human Chronic Low Back Pain Model.

Chabal Charles C Dunbar Peter J PJ Painter Ian I Young Douglas D Chabal Darah C DC

Journal of pain research 20200813

<h4>Purpose</h4>For years, heat has been used for comfort and analgesia is recommended as a first-line therapy in many clinical guidelines. Yet, there are questions that remain about the actual effectiveness of heat for a condition as common as chronic low back pain, and factors such as time of onset, optimal temperature, and duration of effect.<h4>Materials and methods</h4>A randomized double-blinded controlled trial was designed to compare the analgesic response to heat delivered via pulses at ...[more]

PMID: 32884334

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Project description:BackgroundThe role played by the thoracolumbar fascia in chronic low back pain (LBP) is poorly understood. The thoracolumbar fascia is composed of dense connective tissue layers separated by layers of loose connective tissue that normally allow the dense layers to glide past one another during trunk motion. The goal of this study was to quantify shear plane motion within the thoracolumbar fascia using ultrasound elasticity imaging in human subjects with and without chronic low back pain (LBP).MethodsWe tested 121 human subjects, 50 without LBP and 71 with LBP of greater than 12 months duration. In each subject, an ultrasound cine-recording was acquired on the right and left sides of the back during passive trunk flexion using a motorized articulated table with the hinge point of the table at L4-5 and the ultrasound probe located longitudinally 2 cm lateral to the midline at the level of the L2-3 interspace. Tissue displacement within the thoracolumbar fascia was calculated using cross correlation techniques and shear strain was derived from this displacement data. Additional measures included standard range of motion and physical performance evaluations as well as ultrasound measurement of perimuscular connective tissue thickness and echogenicity.ResultsThoracolumbar fascia shear strain was reduced in the LBP group compared with the No-LBP group (56.4% ± 3.1% vs. 70.2% ± 3.6% respectively, p < .01). There was no evidence that this difference was sex-specific (group by sex interaction p = .09), although overall, males had significantly lower shear strain than females (p = .02). Significant correlations were found in male subjects between thoracolumbar fascia shear strain and the following variables: perimuscular connective tissue thickness (r = -0.45, p <.001), echogenicity (r = -0.28, p < .05), trunk flexion range of motion (r = 0.36, p < .01), trunk extension range of motion (r = 0.41, p < .01), repeated forward bend task duration (r = -0.54, p < .0001) and repeated sit-to-stand task duration (r = -0.45, p < .001).ConclusionThoracolumbar fascia shear strain was ~20% lower in human subjects with chronic low back pain. This reduction of shear plane motion may be due to abnormal trunk movement patterns and/or intrinsic connective tissue pathology. There appears to be some sex-related differences in thoracolumbar fascia shear strain that may also play a role in altered connective tissue function.

Project description:Low back pain, a leading cause of disability, is commonly treated by epidural steroid injections that target the anti-inflammatory glucocorticoid receptor (GR). However, their efficacy has been controversial. All currently used epidural steroids also activate the pro-inflammatory mineralocorticoid receptor (MR) with significant potency. Local inflammation of the dorsal root ganglia (DRG), a rat model of low back pain, was used. This model causes static and dynamic mechanical allodynia, cold allodynia and guarding behavior (a measure of spontaneous pain), and activates the MR, with pro-nociceptive effects. In this study, effects of local Dexamethasone (DEX; a glucocorticoid used in epidural injections), and eplerenone (EPL; a second generation, more selective MR antagonist) applied to the DRG at the time of inflammation were examined. Mechanical and spontaneous pain behaviors were more effectively reduced by the combination of DEX and EPL than by either alone. The combination of steroids was particularly more effective than DEX alone or the model alone (3-fold improvement for mechanical allodynia) at later times (day 14). Immunohistochemical analysis of the GR in the DRG showed that the receptor was expressed in neurons of all size classes, and in non-neuronal cells including satellite glia. The GR immunoreactivity was downregulated by DRG inflammation (48%) starting on day 1, consistent with the reduction of GR (57%) observed by Western blot, when compared to control animals. On day 14, the combination of DEX and EPL resulted in rescue of GR immunoreactivity that was not seen with DEX alone, and was more effective in reducing a marker for satellite glia activation/neuroinflammation. The results suggest that EPL may enhance the effectiveness of clinically used epidural steroid injections, in part by enhancing the availability of the GR. Thus, the glucocorticoid-mineralocorticoid interactions may limit the effectiveness of epidural steroids through the regulation of the GR in the DRG.

Project description:BackgroundChronic low back pain (cLBP) is a complex with a heterogenous clinical presentation. A better understanding of the factors that contribute to cLBP is needed for accurate diagnosis, optimal treatment, and identification of mechanistic targets for new therapies. The Back Pain Consortium (BACPAC) Research Program provides a unique opportunity in this regard, as it will generate large clinical datasets, including a diverse set of harmonized measurements. The Theoretical Model Working Group was established to guide BACPAC research and to organize new knowledge within a mechanistic framework. This article summarizes the initial work of the Theoretical Model Working Group. It includes a three-stage integration of expert opinion and an umbrella literature review of factors that affect cLBP severity and chronicity.MethodsDuring Stage 1, experts from across BACPAC established a taxonomy for risk and prognostic factors (RPFs) and preliminary graphical depictions. During Stage 2, a separate team conducted a literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to establish working definitions, associated data elements, and overall strength of evidence for identified RPFs. These were subsequently integrated with expert opinion during Stage 3.ResultsThe majority (∼80%) of RPFs had little strength-of-evidence confidence, whereas seven factors had substantial confidence for either a positive association with cLBP (pain-related anxiety, serum C-reactive protein, diabetes, and anticipatory/compensatory postural adjustments) or no association with cLBP (serum interleukin 1-beta / interleukin 6, transversus muscle morphology/activity, and quantitative sensory testing).ConclusionThis theoretical perspective will evolve over time as BACPAC investigators link empirical results to theory, challenge current ideas of the biopsychosocial model, and use a systems approach to develop tools and algorithms that disentangle the dynamic interactions among cLBP factors.

Project description:We recently showed that patients with different chronic pain conditions (such as chronic low back pain, fibromyalgia, migraine and Gulf War illness) demonstrated elevated brain and/or spinal cord levels of the glial marker 18-kDa translocator protein (TSPO), which suggests that neuroinflammation might be a pervasive phenomenon observable across multiple aetiologically heterogeneous pain disorders. Interestingly, the spatial distribution of this neuroinflammatory signal appears to exhibit a degree of disease specificity (e.g. with respect to the involvement of the primary somatosensory cortex), suggesting that different pain conditions may exhibit distinct 'neuroinflammatory signatures'. To explore this hypothesis further, we tested whether neuroinflammatory signal can characterize putative aetiological subtypes of chronic low back pain patients based on clinical presentation. Specifically, we explored neuroinflammation in patients whose chronic low back pain either did or did not radiate to the leg (i.e. 'radicular' versus 'axial' back pain). Fifty-four patients with chronic low back pain, 26 with axial back pain [43.7 ± 16.6 years old (mean ± SD)] and 28 with radicular back pain (48.3 ± 13.2 years old), underwent PET/MRI with 11C-PBR28, a second-generation radioligand for TSPO. 11C-PBR28 signal was quantified using standardized uptake values ratio (validated against volume of distribution ratio; n = 23). Functional MRI data were collected simultaneously to the 11C-PBR28 data (i) to functionally localize the primary somatosensory cortex back and leg subregions; and (ii) to perform functional connectivity analyses (in order to investigate possible neurophysiological correlations of the neuroinflammatory signal). PET and functional MRI measures were compared across groups, cross-correlated with one another and with the severity of 'fibromyalgianess' (i.e. the degree of pain centralization, or 'nociplastic pain'). Furthermore, statistical mediation models were used to explore possible causal relationships between these three variables. For the primary somatosensory cortex representation of back/leg, 11C-PBR28 PET signal and functional connectivity to the thalamus were: (i) higher in radicular compared to axial back pain patients; (ii) positively correlated with each other; (iii) positively correlated with fibromyalgianess scores, across groups; and finally (iv) fibromyalgianess mediated the association between 11C-PBR28 PET signal and primary somatosensory cortex-thalamus connectivity across groups. Our findings support the existence of 'neuroinflammatory signatures' that are accompanied by neurophysiological changes and correlate with clinical presentation (in particular, with the degree of nociplastic pain) in chronic pain patients. These signatures may contribute to the subtyping of distinct pain syndromes and also provide information about interindividual variability in neuroimmune brain signals, within diagnostic groups, that could eventually serve as targets for mechanism-based precision medicine approaches.

Dataset Information

Properties of Thermal Analgesia in a Human Chronic Low Back Pain Model.

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Properties of Thermal Analgesia in a Human Chronic Low Back Pain Model.

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