Articles: hyperalgesia.
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The neurobiological mechanisms underlying chronic pain associated with cancers are not well understood. It has been hypothesized that factors specifically elevated in the tumor microenvironment sensitize adjacent nociceptive afferents. We show that parathyroid hormone-related peptide (PTHrP), which is found at elevated levels in the tumor microenvironment of advanced breast and prostate cancers, is a critical modulator of sensory neurons. ⋯ We also observed an increase in plasma membrane TRPV1 protein levels after exposure to PTHrP, leading to upregulation in the proportion of TRPV1-responsive neurons, which was dependent on the activity of PKC and Src kinases. Furthermore, co-injection of PKC or Src inhibitors attenuated PTHrP-induced thermal but not mechanical hypersensitivity. Altogether, our results suggest that PTHrP and mild acidic conditions could induce constitutive pathological activation of sensory neurons through upregulation of TRPV1 function and trafficking, which could serve as a mechanism for peripheral sensitization of nociceptive afferents in the tumor microenvironment.
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Sleep deprivation induces hyperalgesia. However, this pro-nociceptive effect is not reflected at the electrophysiological level, since sleep restricted subjects show amplitude reduction of Laser-evoked Potentials (LEP). We aimed to explore the contribution of habituation to this paradoxical LEP amplitude decline. ⋯ TSD induces hyperalgesia and results in attention-dependent enhanced habituation of the P2 component. Increased habituation may--to a substantial degree--explain the TSD-induced LEP-amplitude decline. For this article, a commentary is available at the Wiley Online Library.
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Identification of mechanisms for pain/hyperalgesia following spinal cord injury requires long-term evaluation of individual subjects because of the variability in effect over time for humans. ⋯ Histology revealed that hyperalgesia occurred when there was: (1) damage to spinal white matter; or (2) cystic cavitation; or (3) compression and distortion of the spinal cord without an obvious loss of grey or white matter.
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Int. Immunopharmacol. · Sep 2015
Inflammatory mediators involved in the paw edema and hyperalgesia induced by Batroxase, a metalloproteinase isolated from Bothrops atrox snake venom.
Snake venom metalloproteinases have been described as responsible for several inflammatory effects. In this study, we investigated the edema and hyperalgesia induced in rats by Batroxase, a P-I metalloproteinase from Bothrops atrox venom, along with possible inflammatory mediators involved in these responses. Batroxase or sterile saline was injected into rat paws and the edema and hyperalgesic effects were evaluated for 6h by using a plethysmometer and a Von Frey system, respectively. ⋯ However, Batroxase itself induced minor degranulation of RBL-2H3 mast cells in vitro. Additionally, the inflammatory responses did not seem to be related to prostaglandins, bradykinin or nitric oxide. Our results indicate a major involvement of histamine and leukotrienes in the edema and hyperalgesia induced by Batroxase, which could be related, at least in part, to mast cell degranulation.
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Pulsed radiofrequency (PRF) treatment is a minimally invasive technique with multiple therapeutic applications. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channel mediating Ih may regulate neuropathic pain signaling. This study aimed to determine whether PRF suppresses neuropathic pain by altering HCN channel expression in dorsal root ganglion (DRG) neurons. ⋯ The results showed that thermal hyperalgesia, mechano-allodynia, and mechano-hyperalgesia were lower, and DRG expression levels of HCN1 and HCN2 higher, in the PRF group compared with sham control animals (all P < 0.05 at D14). In conclusion, PRF can upregulate HCN channel expression in the DRG of rats with sciatic nerve CCI. How this regulation of Ih in nociceptive afferents contributes to the suppression of neuropathic pain by PRF remains to be determined.