Articles: hyperalgesia.
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Mol. Cell. Neurosci. · Apr 2016
Downregulation of the spinal dorsal horn clock gene Per1 expression leads to mechanical hypersensitivity via c-jun N-terminal kinase and CCL2 production in mice.
Disturbances of circadian rhythm and dysregulation of clock gene expression are involved in the induction of various neurological disorder states, including chronic pain. However, the relationship between the CNS circadian-clock gene system and nociception remains poorly defined. Significant circadian oscillations of Period (Per1, Per2), Bmal1 and Cryptochrome 1 (Cry1) mRNA expression have been observed in the lumbar spinal dorsal horn of naïve mice. ⋯ Per1 siRNA-induced mechanical hypersensitivity was attenuated with intrathecal treatment of either the JNK inhibitor SP600125 or the selective CCL2 receptor (CCR2) antagonist RS504393, indicating that these intracellular messengers are crucial in mediating the mechanical hypersensitivity following the downregulation of PER1 expression. These results suggest that the downregulation of the spinal dorsal horn clock genes such as Per1 expressed could be crucial in the induction of neuropathic pain following peripheral nerve injury. Modulating clock gene Per1 expression could be a novel therapeutic strategy in alleviating neuropathic pain.
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Acta Anaesthesiol Scand · Apr 2016
Observational StudyPostoperative hyperalgesia does not predict persistent post-sternotomy pain; observational study based on clinical examination.
Persistent post-sternotomy pain is a common problem, but the risk of developing it varies among patients. We sought to find out whether the risk of persistent post-sternotomy pain could be predicted by measuring the area of acute sensory dysfunction around the sternotomy wound. The secondary aim was to determine risk factors for persistent post-sternotomy pain. ⋯ Measuring the area of hyperalgesia in the acute phase does not give any additional information on the risk of developing a persistent post-sternotomy pain. We do thus not recommend measuring the area in this particular group of patients. Evaluation of pain by only a questionnaire risks to overestimate the presence of persistent post-sternotomy pain as compared to clinical examination.
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The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor in the immunoglobulin superfamily. RAGE is localized throughout ascending sensory pathways (skin, peripheral nerve, dorsal root ganglion, spinal cord), and in cell types interacting with sensory neurons (endothelial cells, smooth muscle cells, monocytes and macrophages). Neuronal RAGE expression increases in pathological pain states in humans and rodents, and soluble RAGE attenuates thermal hypoalgesia in diabetic mice. The objective of the present study was to investigate whether pharmacological modulation of RAGE could attenuate mechanical allodynia in rodent pain models. ⋯ These data demonstrate that specific modulation of RAGE effectively attenuates nociceptive sensitivity associated with chronic inflammatory and neuropathic pain states.
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Experimental neurology · Apr 2016
Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury.
Human SCI is frequently associated with chronic pain that is severe and refractory to medical therapy. Most rodent models used to assess pain outcomes in SCI apply moderate injuries to lower thoracic spinal levels, whereas the majority of human lesions are severe in degree and occur at cervical or upper thoracic levels. To better model and understand mechanisms associated with chronic pain after SCI, we subjected adult rats to T3 severe compression or complete transection lesions, and examined pain-related behaviors for three months. ⋯ Notably, satellite glial cells (SGCs) in C6-C8 DRGs exhibited increases in GFAP and connexin-43, suggesting ongoing peripheral sensitization. Carbenoxolone, a gap junction inhibitor, and specific peptide inhibitors of connexin-43, ameliorated established tactile allodynia after severe SCI. Collectively, severe T3 SCI successfully models persistent pain states and could constitute a useful model system for examining candidate translational pain therapies after SCI.
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The purpose of this study was to determine the role of spinal 5-HT2A, 5-HT2B and 5-HT2C receptors in the development and maintenance of formalin-induced long-lasting secondary allodynia and hyperalgesia in rats, as well as their expression in the dorsal root ganglia (DRG) during this process. ⋯ Data suggest that spinal 5-HT2A/2B/2C receptors have pronociceptive effects and participate in the development and maintenance of formalin-induced long-lasting hypersensitivity. These receptors are expressed in DRG and their expression is modulated by formalin.