The journal of pain : official journal of the American Pain Society
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Clinical evidence suggests that vitamin C (Vit C) may protect against the development of complex regional pain syndrome (CRPS) after fracture or surgery. Tibia fracture followed by 4 weeks of cast immobilization (fracture/cast) in rats results in nociceptive, vascular, and bone changes resembling clinical CRPS. In this study, fracture/cast rats were treated with the oxidative stress inhibitors Vit C, N-acetyl cysteine, or 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl to examine their effects on CRPS-related nociceptive and vascular changes. ⋯ Treatments with Vit C and N-acetyl cysteine reduced the oxidative stress markers malondialdehyde in the skin, muscle, and sciatic nerve, and lactate in the gastrocnemius muscle of the fracture/cast limb. Furthermore, Vit C treatment inhibited the post-fracture upregulation of substance P and calcitonin gene-related peptide in the sciatic nerve and the increased expression of the pain-related inflammatory mediators, including interleukin (IL)-6, and nerve growth factor in the skin and IL-1β, and IL-6 in the muscle of the post-fracture/cast limb. These data suggest that oxidative stress may contribute to the nociceptive features of the rat CRPS model.
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Review Comparative Study
The Rodent Tibia Fracture Model: A Critical Review and Comparison with the Complex Regional Pain Syndrome Literature.
Distal limb fracture is the most common cause of complex regional pain syndrome (CRPS), thus the rodent tibia fracture model (TFM) was developed to study CRPS pathogenesis. This comprehensive review summarizes the published TFM research and compares these experimental results with the CRPS literature. The TFM generated spontaneous and evoked pain behaviors, inflammatory symptoms (edema, warmth), and trophic changes (skin thickening, osteoporosis) resembling symptoms in early CRPS. Neuropeptides, inflammatory cytokines, and nerve growth factor (NGF) have been linked to pain behaviors, inflammation, and trophic changes in the TFM model and proliferating keratinocytes were identified as the primary source of cutaneous cytokines and NGF. Tibia fracture also activated spinal glia and upregulated spinal neuropeptide, cytokine, and NGF expression, and in the brain it changed dendritic architecture. B cell-expressed immunoglobulin M antibodies also contributed to pain behavior, indicating a role for adaptive immunity. These results modeled many findings in early CRPS, but significant differences were also noted. ⋯ Multiple neuroimmune signaling mechanisms contribute to the pain, inflammation, and trophic changes observed in the injured limb of the rodent TFM. This model replicates many of the symptoms, signs, and pathophysiology of early CRPS, but most post-fracture changes resolve within 5 months and may not contribute to perpetuating chronic CRPS.
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This review investigated whether youth exhibit attention or interpretation biases toward pain-related information and whether such biases are more pronounced in youth with chronic pain. Three databases were searched to identify studies that assessed attention or interpretation biases using an accepted experimental paradigm. Ten studies were identified, 8 examining attentional biases and 2 examining interpretation biases. ⋯ However, whether pain affects the subsequent deployment of attention is unclear. There is no evidence for biases toward pain in youth without chronic pain, but evidence suggests that anxiety or catastrophizing and attentional control may moderate pain-related attentional biases. There is also weak evidence of interpretation bias in youth with chronic pain compared with those without.
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Many classes of medications have been evaluated in chronic low back pain (cLBP), however their utilization in the community remains unclear. We examined patterns of prescription medication use among Americans with cLBP in a nationally representative, community-based sample. The Back Pain Survey was administered to a representative sample of U.S. adults aged 20 to 69 years (N = 5,103) during the 2009 to 2010 cycle of the National Health and Nutrition Examination Survey. cLBP was defined as self-reported pain in the area between the lower posterior margin of the ribcage and the horizontal gluteal fold on most days for at least 3 months (N = 700). Home-based interviews with pill bottle verification were used to capture commonly prescribed medications for chronic pain. Among the sample of U.S. adults with cLBP aged 20 to 69 years, 36.9% took at least 1 prescription pain medication in the past 30 days; of them, 18.8% used opioids, 9.7% nonsteroidal anti-inflammatory drugs, 8.5% muscle relaxants, and 6.9% gabapentin or pregabalin. Nonpain antidepressants and hypnotics were used by 17.8% and 4.7%, respectively. Opioids were used long-term in 76.9% of cases (median = 2 years) and were frequently coadministered with antidepressants, benzodiazepines, or hypnotics. Ninety-four percent of prescription opioids in the cLBP population were used by individuals with less than a college education. Opioids were the most widely used prescription analgesic class in community-based U.S. adults with cLBP and were often coadministered with other central nervous system-active medications. Opioid use was highly prevalent among less educated Americans with cLBP. ⋯ Because prescription opioid use is an issue of national concern, we examined pain-related prescription medication use in community-dwelling U.S. adults with cLBP. Opioids were the most common prescription pain medication, typically used long-term, in combination with other central nervous system-active agents, and disproportionately among individuals with less than a college education.
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Opioid misuse is regularly associated with disrupted functioning in those with chronic pain. Less work has examined whether alcohol misuse may also interfere with functioning. This study examined frequency of opioid and alcohol misuse in 131 individuals (61.1% female) prescribed opioids for the treatment of chronic pain. ⋯ No differences were indicated between the latter 2 groups. Overall, the observed frequency of opioid misuse was somewhat higher in comparison to previous work (approximately 1 out of every 3 participants), and misuse of both alcohol and opioids was common (approximately 1 out of every 5 participants). While these data are preliminary, they do suggest that issues of substance misuse in those with chronic pain extends beyond opioids alone.