Articles: hyperalgesia.
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Zhonghua Kou Qiang Yi Xue Za Zhi · Mar 2016
[Trigeminal purinergic P2X4 receptor involved in experimental occlusal interference-induced hyperalgesia in rat masseter muscle].
To explore the expression of purinergic p2X4 receptor (P2X4R) in trigeminal ganglion of rats after occlusal interference. Investigation of peripheral receptor mechanism of occlusal interference-induced masticatory muscle pain will aid the development of drug intervention against this condition. ⋯ Increased expression of trigeminal P2X4R involves in the development of occlusal interference-induced masseter hyperalgesia.
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Brain research bulletin · Mar 2016
Peripheral neurosteroids enhance P2X receptor-induced mechanical allodynia via a sigma-1 receptor-mediated mechanism.
The role of peripheral neurosteroids and their related mechanisms on nociception have not been thoroughly investigated. Based on emerging evidence in the literature indicating that neurosteroids and their main target receptors, i.e., sigma-1, GABAA and NMDA, affect P2X-induced changes in neuronal activity, this study was designed to investigate the effect of peripherally injected dehydroepiandrosterone sulphate (DHEAS) and pregnenolone sulfate (PREGS) on P2X receptor-mediated mechanical allodynia in rats. Intraplantar injection of either neurosteroids alone did not produced any detectable changes in paw withdrawal frequency to the innocuous mechanical stimulation in naïve rats. ⋯ In order to investigate the potential role of peripheral sigma-1, GABAA and NMDA receptors in this facilitatory action, we pretreated animals with BD-1047 (a sigma-1 antagonist), muscimol (a GABAA agonist) or MK-801 (a NMDA antagonist) prior to DHEAS or PREGS+αβmeATP injection. Only BD-1047 effectively prevented the facilitatory effects induced by neurosteroids on αβmeATP-induced mechanical allodynia. Collectively, we have shown that peripheral neurosteroids potentiate P2X-induced mechanical allodynia and that this action is mediated by sigma-1, but not by GABAA nor NMDA, receptors.
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TRPV1 is a polymodally activated cation channel acting as key receptor in nociceptive neurons. Its function is strongly affected by kinase-mediated phosphorylation leading to hyperalgesia and allodynia. We present behavioral and molecular data indicating that TRPV1 is strongly modulated by Cdk5-mediated phosphorylation at position threonine-407(mouse)/T406(rat). ⋯ We found that position T406 is critical for the function of TRPV1 by modulating ligand-sensitivity, activation, and desensitization kinetics as well as voltage-dependence. Based on high resolution structures of TRPV1, we discuss T406 being involved in the molecular transition pathway, its phosphorylation leading to a conformational change and influencing the gating of the receptor. Cdk5-mediated phosphorylation of T406 can be regarded as an important molecular switch modulating TRPV1-related behavior and pain sensitivity.
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Interaction of CD200 with its receptor CD200R has an immunoregulatory role and attenuates various types of neuroinflammatory diseases. ⋯ Intrathecal administration of the CD200R1 agonist CD200Fc induces very rapid suppression of neuroinflammatory reactions associated with glial activation and neuropathic pain development. This may constitute a promising and novel therapeutic approach for the treatment of neuropathic pain.
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Here we studied whether and through which mechanisms spinal administration of histamine dihydrochloride (histamine) attenuates pain behavior in neuropathic animals. Experiments were performed in rats with spinal nerve ligation-induced neuropathy and a chronic intrathecal catheter for spinal drug delivery. Mechanical hypersensitivity was assessed with monofilaments while radiant heat was used for assessing nociception. ⋯ Additionally, histamine prevented central (presumably postsynaptically-induced) facilitation of hypersensitivity induced by N-methyl-d-aspartate. The results indicate that spinal histamine at the dose range of 0.1-10µg selectively attenuates mechanical hypersensitivity and ongoing pain in neuropathy. The spinal histamine-induced antihypersensitivity effect involves histamine H2 and GABA(A) receptors and (presumably neuropathy-induced) co-activation of spinal α1-adrenoceptors.