title: Nitrous oxide persistently alleviates pain hypersensitivity in neuropathic rats: A dose-dependent effect.
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.forename: Meric
authors.initials: M
authors.lastname: Ben Boujema
authors.forename: Emilie
authors.initials: E
authors.lastname: Laboureyras
authors.forename: Jan
authors.initials: J
authors.lastname: Pype
authors.forename: Baptiste
authors.initials: B
authors.lastname: Bessière
authors.forename: Guy
authors.initials: G
authors.lastname: Simonnet
mesh_terms: D000588:Amines / Q000627:therapeutic use; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000077206:Gabapentin; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology*; D009609:Nitrous Oxide / Q000627:therapeutic use*; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016896:Treatment Outcome; D005680:gamma-Aminobutyric Acid / Q000627:therapeutic use
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D009609:Nitrous Oxide