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Nitrous oxide persistently alleviates pain hypersensitivity in neuropathic rats: A dose-dependent effect.
Pain Res Manag. 2015 Nov-Dec; 20(6):309-15.PR

Abstract

BACKGROUND

Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N2O) is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of the N-methyl-D-aspartate receptor (NMDAR). The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury.

OBJECTIVE

Using the chronic constriction injury of the sciatic nerve in male rats as a preclinical model of neuropathic pain, the first aim of the present study was to evaluate the lowest N2O concentration and the shortest time of N2O postinjury exposure that would produce persistent relief of neuropathic pain. The second aim was to compare the effects of N2O with gabapentin, a reference drug used in human neuropathic pain relief.

METHODS

Changes in the nociceptive threshold were evaluated using the paw pressure vocalization test in rats.

RESULTS

Among the various N2O concentrations tested, which ranged from 25% to 50%, only 50% N2O single exposure for 1 h 15 min induced a persistent (minimum of three weeks) and significant (60%) reduction in pain hypersensitivity. A single gabapentin dose (75 mg⁄kg to 300 mg⁄kg, intraperitoneally) induced an acute (1 h to 1 h 30 min) dose-dependent effect, but not a persistent effect such as that observed with N2O.

CONCLUSIONS

These preclinical results suggest that N2O is advantageous for long-lasting neuropathic pain relief after sciatic nerve injury compared with other drugs used in humans such as gabapentinoids or NMDAR antagonists. The present preclinical study provides a rationale for developing comparative clinical studies.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26371891

Citation

Ben Boujema, Meric, et al. "Nitrous Oxide Persistently Alleviates Pain Hypersensitivity in Neuropathic Rats: a Dose-dependent Effect." Pain Research & Management, vol. 20, no. 6, 2015, pp. 309-15.
Ben Boujema M, Laboureyras E, Pype J, et al. Nitrous oxide persistently alleviates pain hypersensitivity in neuropathic rats: A dose-dependent effect. Pain Res Manag. 2015;20(6):309-15.
Ben Boujema, M., Laboureyras, E., Pype, J., Bessière, B., & Simonnet, G. (2015). Nitrous oxide persistently alleviates pain hypersensitivity in neuropathic rats: A dose-dependent effect. Pain Research & Management, 20(6), 309-15.
Ben Boujema M, et al. Nitrous Oxide Persistently Alleviates Pain Hypersensitivity in Neuropathic Rats: a Dose-dependent Effect. Pain Res Manag. 2015 Nov-Dec;20(6):309-15. PubMed PMID: 26371891.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Nitrous oxide persistently alleviates pain hypersensitivity in neuropathic rats: A dose-dependent effect. AU - Ben Boujema,Meric, AU - Laboureyras,Emilie, AU - Pype,Jan, AU - Bessière,Baptiste, AU - Simonnet,Guy, Y1 - 2015/09/15/ PY - 2015/9/16/entrez PY - 2015/9/16/pubmed PY - 2016/9/22/medline SP - 309 EP - 15 JF - Pain research & management JO - Pain Res Manag VL - 20 IS - 6 N2 - BACKGROUND: Despite numerous pharmacological approaches, there are no common analgesic drugs that produce meaningful relief for the majority of patients with neuropathic pain. Although nitrous oxide (N2O) is a weak analgesic that acts via opioid-dependent mechanisms, it is also an antagonist of the N-methyl-D-aspartate receptor (NMDAR). The NMDAR plays a critical role in the development of pain sensitization induced by nerve injury. OBJECTIVE: Using the chronic constriction injury of the sciatic nerve in male rats as a preclinical model of neuropathic pain, the first aim of the present study was to evaluate the lowest N2O concentration and the shortest time of N2O postinjury exposure that would produce persistent relief of neuropathic pain. The second aim was to compare the effects of N2O with gabapentin, a reference drug used in human neuropathic pain relief. METHODS: Changes in the nociceptive threshold were evaluated using the paw pressure vocalization test in rats. RESULTS: Among the various N2O concentrations tested, which ranged from 25% to 50%, only 50% N2O single exposure for 1 h 15 min induced a persistent (minimum of three weeks) and significant (60%) reduction in pain hypersensitivity. A single gabapentin dose (75 mg⁄kg to 300 mg⁄kg, intraperitoneally) induced an acute (1 h to 1 h 30 min) dose-dependent effect, but not a persistent effect such as that observed with N2O. CONCLUSIONS: These preclinical results suggest that N2O is advantageous for long-lasting neuropathic pain relief after sciatic nerve injury compared with other drugs used in humans such as gabapentinoids or NMDAR antagonists. The present preclinical study provides a rationale for developing comparative clinical studies. SN - 1918-1523 UR - https://www.unboundmedicine.com/medline/citation/26371891/Nitrous_oxide_persistently_alleviates_pain_hypersensitivity_in_neuropathic_rats:_A_dose_dependent_effect_ L2 - https://doi.org/10.1155/2015/809059 DB - PRIME DP - Unbound Medicine ER -