The journal of pain : official journal of the American Pain Society
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Comparative Study
Smaller amygdala volumes in patients with chronic low back pain as compared to healthy control subjects.
Although preclinical and clinical data strongly support an association between the amygdala and chronic pain by the presence of mood and cognitive disturbances in affected individuals, little attention has been paid to morphometric measurement of the structure in patients with chronic low back pain (CLBP). In the present study, magnetic resonance volumetric and surface analysis, using FMRIB's integrated registration and segmentation tool (FIRST), were performed to compare structural magnetic resonance imaging data obtained from 33 patients with CLBP with those obtained from 33 demographically similar healthy control individuals. Our results indicated that the normalized volumes of the left and right amygdala were significantly smaller in the CLBP group than in the control group. Detailed surface analyses further localized these differences. The degree of volume reduction was different between the left and right amygdala, with a greater involvement of the left side. Both groups exhibited similar significant hemispheric asymmetry for the amygdala (left > right). Similar asymmetry was suggested in the subgroup of 24 unmedicated patients. No significant correlations were found between amygdala volumes and pain characteristics or depressive symptoms. Our study provides in vivo imaging evidence of abnormal morphology of the amygdala in patients with CLBP using a fully automated segmentation method. ⋯ Our study found that patients with CLBP had statistically significantly smaller normalized volumes of the bilateral amygdala, compared with healthy control individuals, with a greater involvement of the left side. These results may help to characterize the impaired affective-cognitive dimension in patients with chronic pain.
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Pain catastrophizing and fear of movement have been identified as key predictors of prolonged work disability after whiplash injury. However, little is known about the processes by which pain catastrophizing and fear of movement affect return to work. This study investigated the mediating role of expectancies on the relations between pain catastrophizing and return to work, and between fear of movement and return to work after whiplash injury. The study sample consisted of 154 individuals with whiplash injury who were enrolled in a multidisciplinary pain rehabilitation program. Participants completed measures of pain catastrophizing, fear of movement, and return-to-work expectancies after admission to a rehabilitation program. A follow-up telephone interview was used to assess work status 1 year after discharge. Consistent with previous research, analyses revealed that expectancies, pain catastrophizing, and fear of movement were significant predictors of return to work at 1-year follow-up. Regression analyses (bootstrapping) revealed that expectancies partially mediated the relation between catastrophizing and return to work. Expectancies completely mediated the relation between fear of movement and return to work. The significant predictive and mediating role of expectancies on return to work argues for the inclusion of expectancies as a specific target of intervention for individuals with whiplash injury. ⋯ The findings suggest that expectancies might be part of the pathways by which pain catastrophizing and fear of movement affect return-to-work outcomes after whiplash injury. The findings argue for greater attention to return-to-work expectancies as a risk factor for problematic recovery outcomes as well as a target of intervention.
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Comparative Study
Differences in the antinociceptive effects and binding properties of propranolol and bupranolol enantiomers.
Recent efforts have suggested that the β-adrenergic receptor (β-AR) system may be a novel and viable therapeutic target for pain reduction; however, most of the work to date has focused on the β(2)-adrenergic receptor (AR). Here, we compared the antinociceptive effects of enantiomeric configurations of propranolol and bupranolol, two structurally similar nonselective β-blocking drugs, against mouse models of inflammatory and chronic pain. In addition, we calculated in silico docking and measured the binding properties of propranolol and bupranolol for all 3 β-ARs. Of the agents examined, S-bupranolol is superior in terms of its antinociceptive effect and exhibited fewer side effects than propranolol or its associated enantiomers. In contrast to propranolol, S-bupranolol exhibited negligible β-AR intrinsic agonist activity and displayed a full competitive antagonist profile at β(1)/β(2)/β(3)-ARs, producing a unique blockade of β(3)-ARs. We have shown that S-bupranolol is an effective antinociceptive agent in mice without negative side effects. The distinctive profile of S-bupranolol is most likely mediated by its negligible β-AR intrinsic agonist activity and unique blockade of β(3)-AR. These findings suggest that S-bupranolol instead of propranolol may represent a new and effective treatment for a variety of painful conditions. ⋯ The S enantiomer of bupranolol, a β-receptor antagonist, shows greater antinociceptive efficacy and a superior preclinical safety profile and it should be considered as a unique β-adrenergic receptor compound to advance future clinical pain studies.
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Randomized Controlled Trial Comparative Study
Manual Physical Therapy versus Surgery for Carpal Tunnel Syndrome: a Randomized Parallel-Group Trial.
This randomized clinical trial investigated the effectiveness of surgery compared with physical therapy consisting of manual therapies including desensitization maneuvers in carpal tunnel syndrome (CTS). The setting was a public hospital and 2 physical therapy practices in Madrid, Spain. One hundred twenty women with CTS were enrolled between February 2013 and January 2014, with 1-year follow-up completed in January 2015. Interventions consisted of 3 sessions of manual therapies including desensitization maneuvers of the central nervous system (physical therapy group, n = 60) or decompression/release of the carpal tunnel (surgical group, n = 60). The primary outcome was pain intensity (mean pain and the worst pain), and secondary outcomes included functional status and symptoms severity subscales of the Boston Carpal Tunnel Questionnaire and the self-perceived improvement. They were assessed at baseline and 1, 3, 6, and 12 months by a blinded assessor. Analysis was by intention to treat. At 12 months, 111 (92%) women completed the follow-up (55/60 physical therapy, 56/60 surgery). Adjusted analyses showed an advantage (all, P < .01) for physical therapy at 1 and 3 months in mean pain (Δ -2.0 [95% confidence interval (CI) -2.8 to -1.2]/-1.3 [95% CI -2.1 to -.6]), the worst pain (Δ -2.9 [-4.0 to -2.0]/-2.0 [-3.0 to -.9]), and function (Δ -.8 [-1.0 to -.6]/-.3 [-.5 to -.1]), respectively. Changes in pain and function were similar between the groups at 6 and 12 months. The 2 groups had similar improvements in the symptoms severity subscale of the Boston Carpal Tunnel Questionnaire at all follow-ups. In women with CTS, physical therapy may result in similar outcomes on pain and function to surgery.
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Sickle cell disease (SCD) is a hemoglobinopathy that affects more than 100,000 individuals in the United States. The disease is characterized by the presence of sickle hemoglobin and recurrent episodes of pain. Some individuals with SCD experience frequent hospitalizations and a high burden of pain. The role of central mechanisms in SCD pain has not been explored. Twenty-five adolescents and young adults with SCD underwent functional magnetic resonance imaging. Participants were stratified into groups with high pain or low pain based on the number of hospitalizations for pain in the preceding 12 months. Resting state functional connectivity was analyzed using seed-based and dual regression independent component analysis. Intrinsic brain connectivity was compared between the high pain and low pain groups, and association with fetal hemoglobin, a known modifier of SCD, was explored. Patients in the high pain group displayed an excess of pronociceptive connectivity such as between anterior cingulate and default mode network structures, such as the precuneus, whereas patients in the low pain group showed more connectivity to antinociceptive structures such as the perigenual and subgenual cingulate. Although a similar proportion of patients in both groups reported that they were on hydroxyurea, the fetal hemoglobin levels were significantly higher in the low pain group and were associated with greater connectivity to antinociceptive structures. These findings support the role of central mechanisms in SCD pain. Intrinsic brain connectivity should be explored as a complementary and objective outcome measure in SCD pain research. ⋯ Altered connectivity patterns associated with high pain experience in patients with sickle cell disease suggest a possible role of central mechanisms in sickle cell pain. Resting state brain connectivity studies should be explored as an effective methodology to investigate pain in SCD.