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


RESULTS
Rats 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.


CONCLUSIONS
Spinal 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.
Sluka
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KA
Graduate Program in Physical Therapy and Rehabilitation Science, Pain Research Program, Neuroscience Graduate Program, University of Iowa, Iowa City, IA 52241, USA. kathleen-sluka@uiowa.edu
Audette
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D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006930:Hyperalgesia / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D018836:Inflammation Mediators / Q000494:pharmacology; D008297:Male; D018482:Muscle, Skeletal / Q000293:injuries / Q000294:innervation / Q000503:physiopathology*; D009619:Nociceptors / Q000201:enzymology* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010812:Physical Stimulation; D020671:Posterior Horn Cells / Q000187:drug effects / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018836:Inflammation Mediators; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D011493:Protein Kinase C