Articles: hyperalgesia.
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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.
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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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In addition to analgesia, opioid agonists may increase pain sensitivity under different conditions varying dose and administration pattern. While opioid hyperalgesia induced by tolerance and withdrawal is largely studied, little is known on the mechanisms underlying ultra-low dose morphine hyperalgesia. This pronociceptive response appears to play an opposing role in morphine analgesia and might have clinical relevance. ⋯ No modulation of MAPK and transcription factors' activity was detected in the thalamus. These results support the concept that selective activation of ERK and JNK on descending pathways plays an important role in ultra-low dose morphine hyperalgesia. The modulation of these signalling processes might improve pain management with opiate analgesics.
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Painful experiences are multilayered, composed of sensory, affective, cognitive and behavioral facets. Whereas it is well accepted that the development of chronic pain is due to maladaptive neuronal changes, the underlying molecular mechanisms, their relationship to the different pain modalities, and indeed the localization of these changes are still unknown. Brain-derived neurotrophic factor (BDNF) is an activity-dependent neuromodulator in the adult brain, which enhances neuronal excitability. ⋯ Injections of recombinant BDNF (into the ACC) or a viral vector synthesizing BDNF (into the ACC or S1) triggered both neuronal hyperexcitability, as shown by elevated long-term potentiation, and sustained pain hypersensitivity. Finally, pharmacological blockade of BDNF-tropomyosin receptor kinase B (TrkB) signaling in the ACC, through local injection of cyclotraxin-B (a novel, highly potent, and selective TrkB antagonist) prevented neuronal hyperexcitability, the emergence of cold hypersensitivity, and passive avoidance behavior. These findings show that BDNF-dependent neuronal plasticity in the ACC, a structure known to be involved in the affective-emotional aspect of pain, is a key mechanism in the development and maintenance of the emotional aspect of chronic pain.