Articles: hyperalgesia.
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The fact that neuropathic pain mechanisms are not well understood is a major impediment in the development of effective clinical treatments. We examined whether the interaction between signal regulatory protein alpha 1 (SIRPα1) and Src homology-2 domain-containing protein tyrosine phosphatase 2 (SHP2), and the downstream spinal SHP2/postsynaptic density 95 (PSD-95)/N-methyl-d-aspartate receptor NR2B subunit signaling cascade play a role in neuropathic pain. Following spinal nerve ligation (L5), we assessed tactile allodynia using the von Frey filament test and analyzed dorsal horn samples (L4-5) by Western blotting, reverse transcription polymerase chain reaction, coimmunoprecipitation, and immunofluorescence. ⋯ Intrathecal administration of NSC-87877 (an SHP2 antagonist; 1, 10, or 100μM/rat) and SIRPα1-neutralizing antibodies (1, 10, or 30μg/rat) suppressed spinal nerve ligation-induced allodynia, spinal SHP2 and NR2B phosphorylation, and SHP2/phosphorylated SHP2-PSD-95 and PSD-95-NR2B/phosphorylated NR2B coprecipitation. SHP2 siRNA led to similar effects as the NSC-87877 and SIRPα1 antibody treatments, except it prevented the allodynia-associated spinal SHP2 expression. In conclusion, our results suggest that a spinal SIRPα1-SHP2 interaction exists that subsequently triggers SHP2/PSD-95/NR2B signaling, thereby playing a role in neuropathic pain development.
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Von Frey monofilaments (VFM) and Electronic von Frey are used as quantitative sensory testing to explore mechanical hyperalgesia. The aim of the study was to determine VFM and Electronic von Frey reproducibility and the time required for testing undamaged areas in volunteers and surgical in-hospital patients. ⋯ Exploration of mechanical allodynia in postoperative patients requires rapid and reliable quantitative sensory testing. Electronic von Frey was more reliable and rapid than VFM in exploring mechanical pain thresholds in undamaged areas in volunteers and patients. Further studies are required to confirm whether these results can be extrapolated to areas affected by surgery.
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Spinal glial and proinflammatory cytokine actions are strongly implicated in pathological pain. Spinal administration of the anti-inflammatory cytokine interleukin (IL)-10 abolishes pathological pain and suppresses proinflammatory IL-1β and tumor necrosis factor alpha (TNF-α). Drugs that bind the cannabinoid type-2 receptor (CB(2)R) expressed on spinal glia reduce mechanical hypersensitivity. ⋯ In spinal gp120 animals, AM1710 prevented bilateral mechanical hypersensitivity. For comparison to immunohistochemistry, IL-1β and TNF-α protein quantification from lumbar spinal and DRG homogenates was determined, and revealed increased DRG IL-1β protein levels from gp120, that was robustly prevented by AM1710 pretreatment. Cannabilactone CB(2)R agonists are emerging as anti-inflammatory agents with pain therapeutic implications.
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Antidepressants are often used for the treatment of neuropathic pain. Clinical studies suggest that the efficacy of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs) for neuropathic pain is greater than that of selective 5-HT reuptake inhibitors (SSRIs). In the present study, we determined the efficacy and mechanisms involved in the antihyperalgesic effects of milnacipran, an SNRI, compared with paroxetine, an SSRI, and maprotiline, a selective NA reuptake inhibitor, using a rat model of neuropathic pain. ⋯ In microdialysis studies, NA and 5-HT concentrations in the spinal dorsal horn were increased after injection of either milnacipran or paroxetine, and only NA was increased after maprotiline. Furthermore, the NA content in the spinal cord of SNL rats was greater than that in normal animals. These findings suggest that an increase in NA in the spinal cord plays an important role in the antihyperalgesic effects of not only NA reuptake inhibitors but also SSRIs.
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Kaohsiung J Med Sci · May 2012
The antinociceptive effect of acetaminophen in a rat model of neuropathic pain.
Acetaminophen is one of the most popular and widely used analgesics for the treatment of pain and fever but few studies have evaluated its effects on neuropathic pain. This study examined the effect of acetaminophen on thermal hyperalgesia, mechanical and cold allodynia in a rat model of neuropathic pain. Male Sprague-Dawley rats were prepared by tightly ligating the left L5 and L6 spinal nerves to produce a model of neuropathic pain. ⋯ The hepatic and renal adverse effect was also assessed by measuring the serum levels of aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen and creatinine. The paw withdrawal thresholds to mechanical stimuli and the thermal withdrawal threshold were increased significantly and withdrawal frequencies to cold stimuli were reduced by acetaminophen administration in a dose-dependent manner. Acetaminophen reduces thermal hyperalgesia, mechanical and cold allodynia in a rat model of neuropathic pain, and might be useful for managing neuropathic pain.