A prolonged nitric oxide-dependent, opioid-mediated antinociceptive effect of hyperbaric oxygen in mice.
Hyperbaric oxygen (HBO(2)) therapy is reported to cause pain relief in several conditions of chronic pain. A single 60-minute session of HBO(2) treatment produced a prolonged antinociceptive effect in mice that persisted for 90 minutes after cessation of treatment. The HBO(2)-induced antinociception was significantly attenuated by pretreatment before HBO(2) exposure with the opioid antagonist naltrexone, the nonspecific nitric oxide synthase (NOS)-inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), and the selective neuronal NOS-inhibitor S-methyl-L-thiocitrulline (SMTC) but not the selective endothelial NOS-inhibitor N(5)-(1-iminoethyl)-L-ornithine (L-NIO). The antinociception was also significantly reduced by central pretreatment with a rabbit antiserum against dynorphin(1-13) but not by rabbit antisera against either beta-endorphin or methionine-enkephalin. The prolonged antinociceptive effect at 90 minutes after HBO(2)-induced treatment was also significantly attenuated by naltrexone but not L-NAME administered 60 minutes after HBO(2) treatment but before nociceptive testing. These findings indicate that the antinociception that persists for 90 minutes after HBO(2) exposure is mediated by nitric oxide (NO) and opioid mechanisms but that the NO involvement is critical during the HBO(2) treatment and not at the time of nociceptive testing. These results are consistent with the concept that HBO(2) may induce an NO-dependent release of opioid peptide to cause a long-acting antinociceptive effect.


CONCLUSIONS
This article presents evidence of a persistent antinociceptive effect of hyperbaric oxygen treatment that is mediated by opioid and NO mechanisms. Further elucidation of the underlying mechanism could identify molecular targets to cause a longer-acting activation of endogenous pain-modulating systems.
Zelinski
Lisa M
LM
Department of Pharmaceutical Sciences, College of Pharmacy, Pullman, Washington, USA.
Ohgami
Yusuke
Y
Chung
Eunhee
E
Shirachi
Donald Y
DY
Quock
Raymond M
RM
D019342:Acetic Acid / Q000008:administration & dosage / Q000633:toxicity; D000698:Analgesia / Q000379:methods*; D000704:Analysis of Variance; D000818:Animals; D002956:Citrulline / Q000031:analogs & derivatives / Q000494:pharmacology; D004399:Dynorphins / Q000378:metabolism; D004744:Enkephalin, Methionine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D006931:Hyperbaric Oxygenation / Q000379:methods*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control; D010147:Pain Measurement / Q000379:methods; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D001615:beta-Endorphin / Q000378:metabolism
D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D002956:Citrulline; D009569:Nitric Oxide; D004744:Enkephalin, Methionine; D009271:Naltrexone; D001615:beta-Endorphin; D004399:Dynorphins; D013890:Thiourea; C086717:S-methylthiocitrulline; D019342:Acetic Acid; D019331:NG-Nitroarginine Methyl Ester