title: Acetaminophen and non-steroidal anti-inflammatory drugs interact with morphine and tramadol analgesia for the treatment of neuropathic pain in rats.
abstract: OBJECTIVE
  Although non-steroidal anti-inflammatory drugs and acetaminophen have no proven efficacy against neuropathic pain, they are frequently prescribed for neuropathic pain patients. We examined whether the combination of opioids (tramadol and morphine) with indomethacin or acetaminophen produce favorable effects on neuropathic pain and compared the efficacy for neuropathic pain with that for inflammatory pain.
  
  
  METHODS
  The carrageenan model was used as the inflammatory pain model while the tibial neuroma transposition (TNT) model was used as the neuropathic pain model. The tibial nerve is transected in the TNT model, with the tibial nerve stump then transpositioned to the lateral aspect of the hindlimb. Neuropathic pain (mechanical allodynia and neuroma pain) is observed after TNT injury. Drugs were administered orally.
  
  
  RESULTS
  In the carrageenan model, all drugs produced anti-allodynic effects and all drug combinations, but not tramadol + indomethacin combination, produced synergistic anti-allodynic effects. In the TNT model, tramadol and morphine, but not acetaminophen and indomethacin, produced anti-neuropathic pain effects. In the combination, with the exception of morphine + acetaminophen combination, both acetaminophen and indomethacin reduced the 50% effective dose (ED50) of tramadol and morphine as compared with the ED50s for the single drug study in the TNT model. The ED50s of tramadol and morphine in the carrageenan combination test were not statistically significantly different from the ED50s in the TNT model combination study.
  
  
  CONCLUSIONS
  The combination of opioids with indomethacin or acetaminophen produced a synergistic analgesic effect both in inflammatory and neuropathic pain with some exceptions. The efficacy of these combinations for neuropathic pain was not different from that for inflammatory pain.
authors.affiliation: Department of Anesthesiology, School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto-shi, Kumamoto, 860-8556, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Shinozaki
authors.affiliation: Department of Anesthesiology, School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto-shi, Kumamoto, 860-8556, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Anesthesiology, School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto-shi, Kumamoto, 860-8556, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nonaka
authors.affiliation: Department of Anesthesiology, School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto-shi, Kumamoto, 860-8556, Japan. yamyam@kumamoto-u.ac.jp.
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009437:Neuralgia / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014147:Tramadol / Q000008:administration & dosage*
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D014147:Tramadol; D009020:Morphine