Nitrous Oxide Persistently Alleviates Pain Hypersensitivity in Neuropathic Rats: A Dose-Dependent Effect. (2015)

• Record Type: Journal Article
• Authors: Ben Boujema, Meric; Laboureyras, Emilie; Pype, Jan; Bessière, Baptiste; Simonnet, Guy
• Is Part Of: Pain research and management. Volume 2015(2015)
• Page Start: 309
• Page End: 315
• Publication Date: 2015
• Subjects: Central sensitization -- Neuropathic pain -- Nitrous oxide; Pain -- Periodicals; Pain -- Treatment -- Periodicals; 616.0472
• DOI: 10.1155/2015/809059
• Languages: English
• ISSNs: 1203-6765

Abstract

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 (N2 O) 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 N2 O concentration and the shortest time of N2 O postinjury exposure that would produce persistent relief of neuropathic pain. The second aim was to compare the effects of N2 O 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 N2 O concentrations tested, which ranged from 25% to 50%, only 50% N2 O 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 N2 O. CONCLUSIONS: These preclinical results suggest that N2 O 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.