The journal of pain : official journal of the American Pain Society
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Despite a fundamental interest in the relationship between structure and function, the relationships between measures of white matter microstructural coherence and functional brain responses to pain are poorly understood. We investigated whether fractional anisotropy (FA) in 2 white matter regions in pathways associated with pain is related to the functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) response to thermal stimulation. BOLD fMRI was measured from 16 healthy male subjects during painful thermal stimulation of the right arm. Diffusion-weighted images were acquired for each subject and FA estimates were extracted from the posterior internal capsule and the cingulum (cingulate gyrus). These values were then included as covariates in the fMRI data analysis. We found BOLD response in the midcingulate cortex (MCC) to be positively related to FA in the posterior internal capsule and negatively related to FA in the cingulum. Our results suggest that the MCC's involvement in processing pain can be further delineated by considering how the magnitude of the BOLD response is related to white matter microstructural coherence and to subjective perception of pain. Considering relationships to white matter microstructural coherence in tracts involved in transmitting information to different parts of the pain network can help interpretation of MCC BOLD activation. ⋯ Relationships between functional brain responses, white matter microstructural coherence, and subjective ratings are crucial for understanding the role of the MCC in pain. These findings provide a basis for investigating the effect of the reduced white matter microstructural coherence observed in some pain disorders on the functional responses to pain.
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Nonspecific chronic spinal pain (NSCSP) is highly disabling. Current conservative rehabilitation commonly includes physical and behavioral interventions, or a combination of these approaches. Physical interventions aim to enhance physical capacity by using methods such as exercise, manual therapy, and ergonomics. Behavioral/psychologically informed interventions aim to enhance behaviors, cognitions, or mood by using methods such as relaxation and cognitive behavioral therapy. Combined interventions aim to target physical and also behavioral/psychological factors contributing to patients' pain by using methods such as multidisciplinary pain management programs. Because it remains unclear whether any of these approaches are superior, this review aimed to assess the comparative effectiveness of physical, behavioral/psychologically informed, and combined interventions on pain and disability in patients with NSCSP. Ten electronic databases were searched for randomized controlled trials (RCTs) including participants reporting NSCSP. Studies were required to have an "active" conservative treatment control group for comparison. Studies were not eligible if the interventions were from the same domain (eg, if the study compared 2 physical interventions). Study quality was assessed used the Cochrane Back Review Group risk of bias criteria. The treatment effects of physical, behavioral/psychologically informed, and combined interventions were assessed using meta-analyses. Twenty-four studies were included. No clinically significant differences were found for pain and disability between physical, behavioral/psychologically informed, and combined interventions. The simple categorization of interventions into physical, behavioral/psychologically informed, and combined could be considered a limitation of this review, because these interventions may not be easily differentiated to allow accurate comparisons to be made. Further work should consider investigating whether tailoring rehabilitation to individual patients and their perceived risk of chronicity, as seen in recent RCTs for low back pain, can enhance outcomes in NSCSP. ⋯ In this systematic review of RCTs in NSCSP, only small differences in pain or disability were observed between physical, behavioral/psychologically informed, and combined interventions.
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Randomized Controlled Trial
Qigong or Yoga versus no intervention in older adults with chronic low back pain - a randomized controlled trial.
The aim of this study was to assess the effectiveness of the reduction of chronic lower back pain in older adults using either yoga classes or qigong classes compared with no intervention. Older adults (65 years of age and older) with chronic low back pain were enrolled in and randomly allocated to: 1) yoga (24 classes, 45 minutes each, during 3 months), 2) qigong (12 classes, 90 minutes each, during 3 months), or 3) a control group who received no additional intervention. The pain intensity item of the Functional Rating Index after 3 months was used as primary outcome parameter. A total of 176 patients were randomized (n = 61 yoga, n = 58 qigong, n = 57 control; mean age 73 ± 5.6 years, 89% female). The mean adjusted pain intensity after 3 months was 1.71 for the yoga group (95% confidence interval [CI], 1.54-1.89), 1.67 for the qigong group (95% CI, 1.45-1.89), and 1.89 for no intervention (95% CI, 1.67-2.11). No statistically significant group differences were observed. Possible explanations for this lack of pain relief might include the ineffectiveness of interventions, inappropriate outcomes, or differences in pain perception and processing in older adults. ⋯ The aim of this study was to assess the effectiveness of the reduction of chronic lower back pain in older adults using either yoga classes or qigong classes compared with no intervention. This 3-armed randomized trial with 176 older adults showed that yoga and qigong were not superior to no treatment in reducing pain and increasing quality of life.
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Chemotherapy-induced peripheral neuropathy (CIPN) is a disruptive and persistent side effect of cancer treatment with paclitaxel. Recent reports showed that paclitaxel treatment results in the activation of Toll-like receptor 4 (TLR4) signaling and increased expression of monocyte chemoattractant protein 1 (MCP-1) in dorsal root ganglion cells. In this study, we sought to determine whether an important consequence of this signaling and also a key step in the CIPN phenotype was the recruitment and infiltration of macrophages into dorsal root ganglia (DRG). Here, we show that macrophage infiltration does occur in a time course that matches the onset of the behavioral CIPN phenotype in Sprague-Dawley rats. Moreover, depletion of macrophages by systemic administration of liposome-encapsulated clodronate (clophosome) partially reversed behavioral signs of paclitaxel-induced CIPN as well as reduced tumor necrosius factor α expression in DRG. Intrathecal injection of MCP-1 neutralizing antibodies reduced paclitaxel-induced macrophage recruitment into the DRG and also blocked the behavioral signs of CIPN. Intrathecal treatment with the TLR4 antagonist lipopolysaccharide-RS (LPS-RS) blocked mechanical hypersensitivity, reduced MCP-1 expression, and blocked the infiltration of macrophages into the DRG in paclitaxel-treated rats. The inhibition of macrophage infiltration into DRG after paclitaxel treatment with clodronate or LPS-RS prevented the loss of intraepidermal nerve fibers (IENFs) observed after paclitaxel treatment alone. These results are the first to indicate a mechanistic link such that activation of TLR4 by paclitaxel leads to increased expression of MCP-1 by DRG neurons resulting in macrophage infiltration to the DRG that express inflammatory cytokines and the combination of these events results in IENF loss and the development of behavioral signs of CIPN. ⋯ This paper shows that activation of innate immunity by paclitaxel results in a sequence of signaling events that results in the infiltration of the dorsal root ganglia by activated macrophages. Macrophages appear to drive the development of behavioral hypersensitivity and the loss of distal epidermal nerve fibers, and hence play an important role in the mechanism of paclitaxel-related neuropathy.
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Awareness of limb position is derived primarily from muscle spindles and higher-order body representations. Although chronic pain appears to be associated with motor and proprioceptive disturbances, it is not clear if this is due to disturbances in position sense, muscle spindle function, or central representations of the body. This study examined position sense errors, as an indicator of spindle function, in participants with unilateral chronic limb pain. The sample included 15 individuals with upper limb pain, 15 with lower limb pain, and 15 sex- and age-matched pain-free control participants. A 2-limb forearm matching task in blindfolded participants, and a single-limb pointer task, with the reference limb hidden from view, was used to assess forearm position sense. Position sense was determined after muscle contraction or stretch, intended to induce a high or low spindle activity in the painful and nonpainful limbs, respectively. Unilateral upper and lower limb chronic pain groups produced position errors comparable with healthy control participants for position matching and pointer tasks. The results indicate that the painful and nonpainful limb are involved in limb-matching. Lateralized pain, whether in the arm or leg, does not influence forearm position sense. ⋯ Painful and nonpainful limbs are involved in bilateral limb-matching. Muscle spindle function appears to be preserved in the presence of chronic pain.