Articles: hyperalgesia.
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Systemic fentanyl induces hyperalgesic priming, long-lasting neuroplasticity in nociceptor function characterized by prolongation of inflammatory mediator hyperalgesia. To evaluate priming at both nociceptor terminals, we studied, in male Sprague Dawley rats, the effect of local administration of agents that reverse type I (protein translation) or type II [combination of Src and mitogen-activated protein kinase (MAPK)] priming. At the central terminal, priming induced by systemic, intradermal, or intrathecal fentanyl was reversed by the combination of Src and MAPK inhibitors, but at the peripheral terminal, it was reversed by the protein translation inhibitor. ⋯ SIGNIFICANCE STATEMENT Fentanyl, acting at the μ-opioid receptor (MOR), induces hyperalgesia and hyperalgesic priming at both the central and peripheral terminal of nociceptors and this is mediated by endoplasmic reticulum Ca2+ signaling. Priming in the central terminal is type II, whereas that in the peripheral terminal is type I. Our findings may provide useful information for the design of drugs with improved therapeutic profiles, selectively disrupting individual MOR signaling pathways, to maintain an adequate long-lasting control of pain.
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Bmc Complem Altern M · Feb 2018
Repeated electroacupuncture treatment attenuated hyperalgesia through suppression of spinal glial activation in chronic neuropathic pain rats.
Cumulated evidence reveals that glial cells in the spinal cord play an important role in the development of chronic neuropathic pain and are also complicated in the analgesic effect of EA intervention. But the roles of microgliacytes and astrocytes of spinal cord in the process of EA analgesia remain unknown. ⋯ Repeated EA can relieve neuropathic pain and mirror-image pain in chronic neuropathic pain rats, which is probably associated with its effect in downregulating glial cell activation of the lumbar spinal cord, the microgliacyte first and astrocyte later.
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The identification of neurobiological markers that predict individual predisposition to pain are not only important for development of effective pain treatments, but would also yield a more complete understanding of how pain is implemented in the brain. In the current study using electroencephalography (EEG), we investigated the relationship between the peak frequency of alpha activity over sensorimotor cortex and pain intensity during capsaicin-heat pain (C-HP), a prolonged pain model known to induce spinal central sensitization in primates. We found that peak alpha frequency (PAF) recorded during a pain-free period preceding the induction of prolonged pain correlated with subsequent pain intensity reports: slower peak frequency at pain-free state was associated with higher pain during the prolonged pain condition. ⋯ Altogether, our findings suggest that pain-free state PAF over relevant sensory systems could serve as a marker of individual predisposition to prolonged pain. Moreover, slowing of PAF in response to prolonged pain could represent an objective marker for subjective pain intensity. Our findings potentially lead the way for investigations in clinical populations in which alpha oscillations and the brain areas contributing to their generation are used in identifying and formulating treatment strategies for patients more likely to develop chronic pain.
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Potassium voltage-gated channel interacting protein 3 (KChIP3), also termed downstream regulatory element antagonist modulator (DREAM) and calsenilin, is a multifunctional protein belonging to the neuronal calcium sensor (NCS) family. Recent studies revealed the expression of KChIP3 in dorsal root ganglion (DRG) neurons, suggesting the potential role of KChIP3 in peripheral sensory processing. Herein, we show that KChIP3 colocalizes with transient receptor potential ion channel V1 (TRPV1), a critical molecule involved in peripheral sensitization during inflammatory pain. ⋯ The KChIP3-TRPV1 interaction reduces the surface localization of TRPV1 and thus alleviates heat hyperalgesia and gait alterations induced by peripheral inflammation. Furthermore, the transmembrane transactivator of transcription (TAT)-31-50 peptide showed analgesic effects on inflammatory hyperalgesia independently of endogenous KChIP3. This work reveals a novel mechanism of peripheral KChIP3 in inflammatory hyperalgesia that is distinct from its classical role as a transcriptional repressor in pain modulation.
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Nerve growth factor (NGF) plays a key role in the initiation as well as the prolonged heightened pain sensitivity of the inflammatory response. Previously, we showed that NGF rapidly augmented both the excitability of isolated rat sensory neurons and the mechanical sensitivity of the rat's hind paw. The increase in excitability and sensitivity was blocked by the myristoylated pseudosubstrate inhibitor of atypical PKCs (mPSI), suggesting that an atypical PKC may play a key regulatory role in generating this heightened sensitivity. ⋯ Intraplantar injection of NGF in the rat hind paw produced a rapid and maintained increase in mechanical sensitivity whose onset was delayed by translation inhibitors. Established NGF-induced hypersensitivity could be transiently reversed by injection of rapamycin or mPSI. These results suggest that NGF produces a rapid increase in the synthesis of PKMζ protein in the paw that augments neuronal sensitivity and that the ongoing translational expression of PKMζ plays a critical role in generating as well as maintaining the heightened sensitivity produced by NGF.