Nitrous oxide (N2O) prevents latent pain sensitization and long-term anxiety-like behavior in pain and opioid-experienced rats.
Neuropharmacology. 2007-11-01; 53(6): 733-740
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1. Neuropharmacology. 2007 Nov;53(6):733-40. Epub 2007 Aug 14.
Nitrous oxide (N2O) prevents latent pain sensitization and long-term anxiety-like
behavior in pain and opioid-experienced rats.
Bessière B(1), Richebé P, Laboureyras E, Laulin JP, Contarino A, Simonnet G.
(1)Université Bordeaux 2, Université Bordeaux 1, CNRS, UMR 5227, Bordeaux,
Improving rehabilitation after a severe tissue injury does not only require a
reduction in pain, but also requires alleviation of negative affects,
particularly anxiety. Although opioids remain unsurpassed analgesics to relieve
moderate to severe pain, it has been shown that they also induce latent pain
sensitization leading to long-lasting hyperalgesia via
N-methyl-D-aspartate-(NMDA)-dependent pronociceptive systems. The present study
evaluated the ability of nitrous oxide (N2O), a gas with NMDA antagonist
properties, to prevent latent pain sensitization and long-term anxiety-like
behavior (ALB) in rats with pain and opioid experiences. On D0, the
pro-inflammatory drug carrageenan was injected in one hind paw of rats treated
with fentanyl (4×100 microg/kg subcutaneously). Nociceptive threshold was
evaluated with the paw pressure vocalization test. Rats were re-exposed to
carrageenan or exposed to repeated non-nociceptive environmental stress (NNES)
2-3 weeks later. Rats were also challenged in the elevated plus-maze 2 weeks
after fentanyl administration for evaluating ALB. The preventive effects of a
single 4 h 50/50% N2O-O2 exposure performed on D0 was evaluated. Fifty percent
N2O strongly reduced hyperalgesia induced by a first inflammation and its
enhancement by fentanyl, and prevented exaggerated hyperalgesia induced by second
inflammatory pain or NNES. Moreover, we provide first evidence that a high
fentanyl dose induces long-term ALB 2 weeks after its administration. When
associated with fentanyl, 50% N2O prevented such long-term ALB. These results
suggest that a single exposure to N2O could improve post-injury pain management
and facilitate rehabilitation especially when potent analgesics as opioids have
to be used.
PMID: 17884109 [Indexed for MEDLINE]