Enkephalinase Inhibition Prevented Tolerance to Nitrous Oxide Analgesia in Rats

Rupreht, J.; Ukponmwan, O.E.; Dworacek, B.; Admiraal, P.V.; Dzoljic, M.R.

doi:10.1111/j.1399-6576.1984.tb02132.x

Cited by 25 publications

(5 citation statements)

References 13 publications

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“…However, it was suggested that exposure to N20 results in a decrease ofopiate receptor density (1 1) which might explain the development of tolerance to the NpO-induced antinociceptive effect. I t is not clear whether this is the only phenomenon responsible for tolerance to N20-analgesia, since tolerance to Nz0-antinociception in rats has been prevented by inhibition of enkephalinase (12). This, in turn, might indicate an impaired release of endorphins during N2O-induced tolerance.…”

Section: Discussionmentioning

confidence: 99%

Tolerance to Nitrous Oxide in Volunteers

Rupreht

Dworacek

Bonke

et al. 1985

Acta Anaesthesiol Scand

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Nociception and loss of awareness during exposure to anaesthetic concentration of nitrous oxide (N2O) were studied in eight male medical students. The cold water nociception test, where a hand is immersed in 0 degree C stirred water, was used for measurement of nociception. At irregular intervals an auditory command was given to oppose two fingers, and this served to monitor consciousness. The selected inspiratory concentration of N2O used per individual was sufficient to induce a loss of consciousness for more than 2.5 min, within 10 min of exposure to N2O. This concentration of N2O varied from 60% to 80%. The experimental exposure to N2O lasted 3 h. In all volunteers significant antinociception was observed within 2 min of exposure to N2O. The maximal analgesic effect was observed between 20 and 30 min of exposure to N2O. The analgesic effect of N2O gradually decreased and was absent in all eight volunteers within 150 min. Two volunteers regained consciousness at 77 and 91 min of exposure, whilst still breathing 60 and 80% N2O. These results show that tolerance to antinociceptive effects of N2O in man rapidly develops and that awareness may occur in some volunteers during prolonged exposure to N2O.

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Section: Discussionmentioning

confidence: 99%

Tolerance to Nitrous Oxide in Volunteers

Rupreht

Dworacek

Bonke

et al. 1985

Acta Anaesthesiol Scand

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“…Using cold-pressor pain, acute tolerance was not observed during a 40-minute administration of up to 40% N 2 O (Pirec et al, 1995) but was found during a 120-min administration of 30-40% N 2 O . Animal research suggests that tolerance develops to N 2 O's antinociceptive effects (Berkowitz et al, 1977;Berkowitz et al, 1979;Rupreht et al, 1984), but this finding is not universal (Shingu et al, 1985) and may depend on rat strain (Fender et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Nitrous oxide analgesia in humans: acute and chronic tolerance

Ramsay¹,

Rothen²,

Prall³

et al. 2005

Pain

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Electrical tooth stimulation was used to investigate whether humans develop tolerance to nitrous oxide (N 2 O) analgesia within a single administration as well as over repeated administrations. In a double-blind cross-over experiment, 77 subjects received a 40-minute administration of 38% N 2 O at one session and placebo gas at the other. The sessions were separated by 1 week and the order of gas administration was counterbalanced. Acute analgesic tolerance developed for pain threshold but not for detection threshold. There was no evidence of a hyperalgesic rebound effect following cessation of the N 2 O administration. In a second double-blind experiment, 64 subjects received both 30-min of placebo gas and 30-min of 35% N 2 O, separated by a 35-min gas wash-out period, during each of 5 sessions. Sensory thresholds were assessed prior to drug or placebo administration (baseline) and between 7-12 min and 25-30 min of gas administration. A control group of 16 subjects received only placebo gas at these 5 sessions. During a sixth session, the experimental procedures were similar to the previous sessions except that the control group received N 2 O for the first time and the experimental group was sub-divided to test for conditioned drug effects. For both detection and pain threshold measures, acute tolerance developed during the initial N 2 O exposure and chronic tolerance developed over repeated administrations. Although chronic tolerance developed, a test for Pavlovian drug conditioning found no evidence of conditioned effects on sensory thresholds. In conclusion, acute and chronic tolerance develop to N 2 O's analgesic effects in humans.

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“…The strain which is unresponsive to N 2 O has lower basal levels of opioid peptides and unlike the responsive strain, endogenous opiate peptide levels do not increase following morphine administration [28]. Earlier it had been suggested that acute depletion of opiate peptides in the central nervous system causes acute tolerance to N 2 O based on the finding that maintaining high levels of enkephalin with an enkephalinase inhibitor prevented the development of acute tolerance in rats [29].…”

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confidence: 99%