The journal of pain : official journal of the American Pain Society
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The aim of this study was to examine the association and changes over time between headaches with or without somatic pain and the self-reported use of pain medication. The study further examined whether the law amendment in 2003 in Norway releasing the sale of nonprescription drugs to shops has changed these relationships. The study is on the basis of repeated self-report cross-sectional studies from 1998 to 2012 in Norway. A total of 27,247 adults were included. As expected, there was a strong association between headache, especially headache with comorbid somatic pain and consumption of prescription versus nonprescription analgesics, although the overall consumption decreased slightly after 2003. We conclude that the strong association between especially headache, whether complicated by somatic pain or not, and the consumption of prescription-free analgesics did not seem to be negatively affected by the prescription regulatory changes. The very high use of nonprescription medication among headache patients suggests the need for continued observation and information regarding the risk of medication-overuse headache. ⋯ In Norway, headache was strongly associated with use of over-the-counter analgesics, for other somatic pain prescription analgesics were equally common. Between 1998 and 2012 headache and related analgesic consumption was reduced and other somatic pain increased. Making over-the-counter analgesics available outside pharmacies in 2003 did not increase the self-reported intake.
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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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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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Laboratory-based studies show that acute aerobic and isometric exercise reduces sensitivity to painful stimuli in young healthy individuals, indicative of a hypoalgesic response. However, little is known regarding the effect of aging on exercise-induced hypoalgesia (EIH). The purpose of this study was to examine age differences in EIH after submaximal isometric exercise and moderate and vigorous aerobic exercise. Healthy older and younger adults completed 1 training session and 4 testing sessions consisting of a submaximal isometric handgrip exercise, vigorous or moderate intensity stationary cycling, or quiet rest (control). The following measures were taken before and after exercise/quiet rest: 1) pressure pain thresholds, 2) suprathreshold pressure pain ratings, 3) pain ratings during 30 seconds of prolonged noxious heat stimulation, and 4) temporal summation of heat pain. The results revealed age differences in EIH after isometric and aerobic exercise, with younger adults experiencing greater EIH compared with older adults. The age differences in EIH varied across pain induction techniques and exercise type. These results provide evidence for abnormal pain modulation after acute exercise in older adults. ⋯ This article enhances our understanding of the influence of a single bout of exercise on pain sensitivity and perception in healthy older compared with younger adults. This knowledge could help clinicians optimize exercise as a method of pain management.
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Pain involving several body regions generally represents nervous system pathophysiology shifting from predominantly peripheral to more central. In adults, higher widespread pain scores are clinically meaningful and confer risk for poor response to treatment. It is unknown whether widespread pain is similarly important in children. To address this gap, we conducted an observational study examining 1) associations between widespread pain and functional impairment and health-related quality of life (HRQOL) in clinical pediatric samples, and 2) associations among sociodemographic factors and pain catastrophizing with widespread pain scores. Participants were 166 children aged 10 to 18 years from 3 samples (acute pain, presurgery, chronic pain). Children self-reported pain intensity, pain catastrophizing, functional impairment, and HRQOL. Children indicated pain locations on a body diagram, which was coded using the American College of Rheumatology definition of widespread pain. Results revealed higher widespread pain scores were associated with greater functional impairment with routine activities (F = 3.15, P = .02) and poorer HRQOL (F = 3.29, P = .02), adjusting for pain intensity, study group, and demographic characteristics. Older age (B = .11, P = .02), and Hispanic ethnicity (B = .67, P = .04) were associated with higher widespread pain scores. Findings support incorporating evaluation of widespread pain into pediatric pain assessment. Future research is needed to examine the longitudinal effect of widespread pain on children's treatment outcomes. ⋯ This article examines the association between widespread pain scores and functional impairment and HRQOL in community and clinical samples of children. Assessment of the spatial distribution of the pain experience provides unique information that may identify children at risk for poorer health.