title: Effects of intrathecal opioids combined with low-dose naloxone on motilin and its receptor in a rat model of postoperative pain.
abstract: OBJECTIVE
  To investigate the effects of intrathecal morphine and fentanyl combined with low-dose naloxone on the expression of motilin and its receptor in a rat model of postoperative pain.
  
  
  METHODS
  An intrathecal catheter was implanted, and saline, opioids (morphine and fentanyl) and naloxone were intrathecally administered 7 days later. An incisional pain model was established to induce pain behaviors in rats by unilateral plantar incision. Thermal hyperalgesia and mechanical allodynia were measured by using a radiant heat and electronic Von Frey filament, respectively. The expression of motilin in the hippocampus, stomach, duodenum, and plasma was determined by ELISA; and the expression of motilin receptor in the hippocampus was detected by Western blot assay.
  
  
  RESULTS
  Motilin and its receptor were detected in the hippocampus. Acute incisional pain increased the motilin expression in the hippocampus and duodenum, while decreasing its expression in the gastric body and plasma. Postoperative analgesia with morphine+fentanyl upregulated the expression of motilin in the hippocampus; however, motilin was downregulated in peripheral sites. Naloxone at 1 ng/kg restored motilin to baseline levels. Acute pain, morphine+fentanyl, and naloxone all induced the expression of motilin receptor in the hippocampus.
  
  
  CONCLUSIONS
  Acute pain, postoperative analgesia with opioids, and naloxone significantly impacted the expression of hippocampal and peripheral motilin. Variation trends in all sites were not identical. Intrathecal injection of low-dose naloxone upregulated paw withdrawal thermal latency and enhanced the analgesic effects of opioids. The findings presented here provide a new basis for central and peripheral regulations in GI motility, clinical postoperative analgesia, and management of analgesic complications.
authors.affiliation: Department of Anesthesiology, The Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Artificial Cell, Tianjin 300170, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The Third Central Hospital of Tianjin, Tianjin, China; Tianjin Key Laboratory of Artificial Cell, Tianjin 300170, China. Electronic address: gaobaozhumed@163.com.
authors.forename: Baozhu
authors.initials: B
authors.lastname: Gao
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Pain Management Center, The Second Hospital of Tianjin Medical University, Tianjin 300203, China.
authors.forename: Baosen
authors.initials: B
authors.lastname: Zheng
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: He
authors.initials: H
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou 221002, China.
authors.forename: Jun-Li
authors.initials: JL
authors.lastname: Cao
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007278:Injections, Spinal; D009037:Motilin / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000378:metabolism; D009270:Naloxone / Q000008:administration & dosage*; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011964:Receptors, Gastrointestinal Hormone / Q000096:biosynthesis*; D018013:Receptors, Neuropeptide / Q000096:biosynthesis*; D016896:Treatment Outcome; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; D009270:Naloxone; D009037:Motilin
keywords: Gastrointestinal motility; Hippocampus; Incisional pain; Motilin; Motilin receptor; Naloxone