Activation of Gi induces mechanical hyperalgesia poststress or inflammation.
In studies of the role of primary afferent nociceptor plasticity in the transition from acute to chronic pain we recently reported that exposure to unpredictable sound stress or a prior inflammatory response induces long-term changes in the second messenger signaling pathway, in nociceptors, mediating inflammatory hyperalgesia; this change involves a switch from a G(s)-cAMP-PKA to a G(i)-PKCepsilon signaling pathway. To more directly study the role of G(i) in mechanical hyperalgesia we evaluated the nociceptive effect of the G(i) activator, mastoparan. Intradermal injection of mastoparan in the rat hind paw induces dose-dependent (0.1 ng-1 microg) mechanical hyperalgesia. The highly selective inhibitors of G(i), pertussis toxin, and of protein kinase C epsilon (PKCepsilon), PKCepsilonV(1-2), both markedly attenuate mastoparan-induced hyperalgesia in stressed rats but had no effect on mastoparan-induced hyperalgesia in unstressed rats. Similar effects were observed, at the site of nociceptive testing, after recovery from carrageenan-induced inflammation. These studies provide further confirmation for a switch to a G(i)-activated and PKCepsilon-dependent signaling pathway in primary mechanical hyperalgesia, induced by stress or inflammation.
Dina
O A
OA
Department of Medicine, Program in Oral and Maxillofacial Surgery, Room C555, 521 Parnassus Avenue, San Francisco, CA 94143, USA.
Khasar
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SG
Gear
R W
RW
Levine
J D
JD
D000818:Animals; D004305:Dose-Response Relationship, Drug; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D006930:Hyperalgesia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D007249:Inflammation / Q000150:complications; D036341:Intercellular Signaling Peptides and Proteins; D007509:Irritants; D008297:Male; D009619:Nociceptors / Q000378:metabolism*; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010455:Peptides; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications; D014862:Wasp Venoms
D036341:Intercellular Signaling Peptides and Proteins; D007509:Irritants; D010455:Peptides; D014862:Wasp Venoms; C037500:mastoparan; D051744:Protein Kinase C-epsilon; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D019205:GTP-Binding Protein alpha Subunits, Gs