Articles: hyperalgesia.
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Interleukin-6 (IL-6) is an inflammatory cytokine known to modulate muscle pain. However, the mechanisms underlying this effect still remain unclear. Here we show that the injection of IL-6 into mice gastrocnemius muscle evoked a time- and dose-dependent mechanical hyperalgesia. ⋯ Simultaneous flow cytometry measurements revealed that ERK, p38 MAPK and JNK were phosphorylated as early as 5 min after IL-6 injection. These findings provided new evidence indicating that IL-6 exerts a relevant role in the development and maintenance of muscular hyperalgesia. The IL-6-mediated muscular pain response involves resident cell activation, polymorphonuclear cell infiltration, cytokine production, prostanoids and sympathomimetic amines release and the activation of intracellular pathways, especially MAPKs.
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Painful neuropathy is a common complication of diabetes. Particularly in the early stage of diabetic neuropathy, patients are characterized by burning feet, hyperalgesia to heat, and mechanical stimuli, as if residual nociceptors were sensitized. Such symptoms are barely explained by common pathophysiological concepts of diabetic neuropathy. ⋯ Diabetic C-fibers show exaggerated sensitivity to hyperglycemic hypoxia with and without additional acidosis, conditions that are thought to mimic ischemic episodes in diabetic nerves. Ongoing C-fiber discharge is known to induce spinal sensitization. Together with altered receptor and ion channel expressions this may contribute to painful episodes in diabetic neuropathy.
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Excessive cervical facet capsular ligament stretch has been implicated as a cause of whiplash-associated disorders following rear-end impacts, but the pathophysiological mechanisms that produce chronic pain in these cases remain unclear. Using a rat model of C6-C7 cervical facet joint capsule stretch that produces sustained mechanical hyperalgesia, the presence of neuronal hyperexcitability was characterized 7 days after joint loading. Extracellular recordings of spinal dorsal horn neuronal activity between C6 and C8 (117 neurons) were obtained from anesthetized rats, with both painful and non-painful behavioral outcomes established by the magnitude of capsule stretch. ⋯ The proportion of cells in the deep laminae that responded as wide dynamic range neurons also was increased in the painful group relative to non-painful or sham groups (p<0.0348). These findings suggest that excessive facet capsule stretch, while not producing visible tearing, can produce functional plasticity of dorsal horn neuronal activity. The increase in neuronal firing across a range of stimulus magnitudes observed at day 7 post-injury provides the first direct evidence of neuronal modulation in the spinal cord following facet joint loading, and suggests that facet-mediated chronic pain following whiplash injury is driven, at least in part, by central sensitization.
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Central sensitisation is associated with chronic pain in whiplash patients. Predicting which patients will develop central sensitisation is difficult but patient expectations of recovery predict a variety of outcomes in whiplash patients. ⋯ Whiplash patients who expect 'never to get better' or 'don't know' have a much higher likelihood of developing at least one sign of central sensitisation 3 months after their collision.
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Burn injury induces severe pain that can be refractory to existing pharmacotherapies. The underlying mechanism of burn pain remains unclear. We previously established an animal model and reported that unilateral burn injury induces chronic and bilateral mechanical allodynia, which is associated with central sensitization and microglial activation in the spinal cord dorsal horn. Modulation of the activity of microglia and p38 mitogen-activated protein kinase (MAPK) has been shown to ameliorate neuropathic pain in several nerve-injury pain models. In the present study, we show in this rat model that daily treatment with the microglial inhibitor minocycline (10 mg/kg), administered at the time of burn injury and for 7 days thereafter, significantly attenuates ipsilateral and contralateral allodynia as assessed up to 1 month following burn injury. These sensory changes are paralleled by significant suppression of evoked hyperexcitability of dorsal-horn neurons and of the expression of phosphorylated p38 (phospho-p38) in OX42+ microglial cells within the dorsal horn. Our results suggest that modulation of inflammation at early times after burn injury may have long-lasting effects, attenuating central neuropathic mechanisms which contribute to pain after burn injury. ⋯ We demonstrate, in a rodent model of burn-associated pain, that the microglial inhibitor minocycline, delivered at the time of burn injury and for 1 week thereafter, has long-lasting effects, attenuating microglial activation and neuronal hyperresponsiveness in the dorsal horns, and ameliorating allodynia for at least 1 month.