Articles: hyperalgesia.
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Opioid analgesics are commonly used to manage moderate to severe pain. However, the long-term use of opioids could lead to opioid tolerance (OT) and opioid-induced hyperalgesia (OIH). Distinguishing OIH from OT would impact the practice of opioid therapy because opioid dose adjustment may differentially influence OT and OIH. ⋯ A key difference in clinical outcome is that OT and OIH could be improved and exacerbated by opioid dose escalation, respectively. Our survey results revealed a significant knowledge gap in some responders regarding differential diagnosis and management of OT and OIH. The results also identified several issues, such as opioid dose adjustment and clinical comorbidities related to OT and OIH, which require future patient-based studies.
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Complex regional pain syndrome (CRPS) is a painful, disabling, chronic condition whose etiology remains poorly understood. The recent suggestion that immunological mechanisms may underlie CRPS provides an entirely novel framework in which to study the condition and consider new approaches to treatment. Using a murine fracture/cast model of CRPS, we studied the effects of B-cell depletion using anti-CD20 antibodies or by performing experiments in genetically B-cell-deficient (μMT) mice. ⋯ Additional experiments demonstrated that complement system activation and deposition of membrane attack complexes were partially blocked by anti-CD20+ treatment. Collectively, our results suggest that CD20-positive B cells produce antibodies that ultimately support the CRPS-like changes in the murine fracture/cast model. Therapies directed at reducing B-cell activity may be of use in treating patients with CRPS.
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The aim of this study was to investigate the predictive value of exercise-induced hypoalgesia (EIH) profile on pain intensity induced by nerve injury in a rat model. EIH was tested by evaluating the percentage of withdrawal responses to a train of 30 mechanical stimuli on the hind paw before and after 180 seconds of exercise on a rotating rod. The rats were grouped into low, medium, and high EIH based on their reduction in the percentage of withdrawal responses before and after exercise. Rats from each group then underwent left sciatic nerve constriction injury. Mechanical allodynia, mechanical hyperalgesia, and heat allodynia were assessed in the affected and contralateral hind paws prior to and 3 and 7 days following the procedure. The low EIH rats demonstrated increased hypersensitivity at baseline and developed significantly more severe heat allodynia, mechanical allodynia, and hyperalgesia 3 and 7 days following the injury compared to the medium and high EIH rats. Moreover, the low EIH rats developed contralateral heat allodynia following the injury. The EIH of habituated and nonhabituated rats was compared to study the role of stress on the hypoalgesic effect. No significant differences were found between the habituated and nonhabituated rats at baseline and 1 and 5 minutes after the exercise. ⋯ EIH profile was found to be predictive of pain severity following nerve injury. It may suggest that selected patients with faulty pain modulation are at risk for developing chronic pain following injury or surgical procedures. EIH may represent a preoperative means to detect this predisposition and enable proactive management.
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We previously showed that peripheral noxious input after spinal cord injury (SCI) inhibits beneficial spinal plasticity and impairs recovery of locomotor and bladder functions. These observations suggest that noxious input may similarly affect the development and maintenance of chronic neuropathic pain, an important consequence of SCI. In adult rats with a moderate contusion SCI, we investigated the effect of noxious tail stimulation, administered 1 day after SCI on mechanical withdrawal responses to von Frey stimuli from 1 to 28 days after treatment. ⋯ In addition, immunohistochemical analysis revealed distinct morphological signs of apoptosis in neurons and microglia at 24h after stimulation. Interestingly, expression of the inflammatory mediator NFκB was unaltered by nociceptive stimulation. These results suggest that noxious input caudal to the level of SCI can increase the onset and expression of behavioral responses indicative of pain, potentially involving TNFα signaling.
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Journal of neurochemistry · Nov 2014
Reactive oxygen species and lipid peroxidation inhibitors reduce mechanical sensitivity in a chronic neuropathic pain model of spinal cord injury in rats.
Chronic neuropathic pain is a common consequence of spinal cord injury (SCI), develops over time and negatively impacts quality of life, often leading to substance abuse and suicide. Recent evidence has demonstrated that reactive oxygen species (ROS) play a role in contributing to neuropathic pain in SCI animal models. This investigation examines four compounds that reduce ROS and the downstream lipid peroxidation products, apocynin, 4-oxo-tempo, U-83836E, and tirilazad, and tests if these compounds can reduce nocioceptive behaviors in chronic SCI animals. ⋯ Injury or trauma to nervous tissue leads to increased concentrations of ROS in the surviving tissue. Further damage from ROS molecules to dorsal lamina neurons leads to membrane excitability, the physiological correlate of chronic pain. Chronic pain is difficult to treat with current analgesics and this research will provide a novel therapy for this disease.