Ethanol withdrawal-associated allodynia and hyperalgesia: age-dependent regulation by protein kinase C epsilon and gamma isoenzymes.
Ethanol (EtOH) withdrawal increases sensitivity to painful stimuli in adult rats. In this study, withdrawal from a single, acute administration of EtOH dose-dependently produced mechanical allodynia and thermal hyperalgesia in postnatal day 7 (P7) rats. In contrast, P21 rats exhibited earlier and more prolonged mechanical allodynia but not thermal hyperalgesia. For both P7 and P21 rats, blood and spinal cord EtOH levels peaked at 30 minutes after administration, with P7 rats achieving overall higher spinal cord concentrations. Protein kinase C (PKC) has been implicated in mediating pain responses. Inhibitory PKC- and gamma-specific peptides attenuated mechanical allodynia and thermal hyperalgesia in P7 rats, whereas only the PKCgamma inhibitor prevented mechanical allodynia in P21 rats. Immunoreactive PKC in dorsal root ganglion and PKCgamma in lumbar spinal cord increased at 6 hours after EtOH administration in P7 rats. In P21 rats, the density of PKC immunoreactivity remained unchanged, whereas the density of PKCgamma immunoreactivity increased and translocation occurred. These studies demonstrate developmental differences in neonatal nociceptive responses after withdrawal from acute EtOH and implicate a role for specific PKC isozymes in EtOH withdrawal-associated allodynia and hyperalgesia.


CONCLUSIONS
This study examines age-specific nociceptive responses after ethanol exposure by using 2 different ages of rats. The results suggest that ethanol age-dependently alters sensitivity to mechanical and thermal stimuli via specific protein kinase C isozymes. These results begin to ascertain the mechanisms that produce abnormal pain after alcohol exposure.
Shumilla
Jennifer A
JA
Department of Anesthesiology, Stanford University School of Medicine, Stanford, CA, USA.
Liron
Tamar
T
Mochly-Rosen
Daria
D
Kendig
Joan J
JJ
Sweitzer
Sarah M
SM
D000367:Age Factors; D000375:Aging / Q000502:physiology; D020268:Alcohol-Induced Disorders, Nervous System / Q000201:enzymology* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000187:drug effects* / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000201:enzymology* / Q000503:physiopathology
D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D010455:Peptides; D000431:Ethanol; C087857:protein kinase C gamma; D011493:Protein Kinase C; D051744:Protein Kinase C-epsilon