Activation of protein kinase C in the spinal cord produces mechanical hyperalgesia by activating glutamate receptors, but does not mediate chronic muscle-induced hyperalgesiaReport as inadecuate




Activation of protein kinase C in the spinal cord produces mechanical hyperalgesia by activating glutamate receptors, but does not mediate chronic muscle-induced hyperalgesia - Download this document for free, or read online. Document in PDF available to download.

Molecular Pain

, 2:13

First Online: 03 April 2006Received: 03 January 2006Accepted: 03 April 2006

Abstract

BackgroundProtein kinase C PKC in the spinal cord appears to mediate chronic injury-induced pain, but not acute nociceptive pain. Muscle insult results in increased release of glutamate spinally, and hyperalgesia that is reversed by spinal blockade of NMDA and non-NMDA glutamate receptors. Therefore, we hypothesized that spinal activation of PKC 1 mediates the late phase of hyperalgesia 1 week after muscle insult, and 2 produces mechanical hyperalgesia through activation of NMDA and non-NMDA glutamate receptors.

ResultsRats were implanted with intrathecal catheters for delivery of drugs directly to the spinal cord. Mechanical withdrawal thresholds of the paw were determined using von Frey filaments. Intrathecal phorbol 12,13 dibutyrate PDBu produced a dose-dependent decrease in the mechanical withdrawal threshold of the paw that was prevented by pretreatment with the PKC inhibitor, GF109203X. Pretreatment with an NMDA receptor antagonist AP5 or a AMPA-kainate receptor antagonist NBQX prevented the decrease in mechanical withdrawal threshold by PDBu. Two injections of acidic saline in the gastrocnemius muscle decreased the mechanical withdrawal thresholds of the paw bilaterally 24 h and 1 week after the second injection. However, blockade PKC in the spinal cord had no effect on the decreased withdrawal thresholds of the paw when compared to vehicle controls.

ConclusionSpinal activation of PKC produces mechanical hyperalgesia of the paw that depends on activation of NMDA and non-NMDA receptors. Chronic muscle-induced mechanical hyperalgesia, on the other hand, does not utilize spinal PKC.

Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-2-13 contains supplementary material, which is available to authorized users.

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Author: KA Sluka - KM Audette

Source: https://link.springer.com/







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