title: Nitric oxide in the hippocampal cortical area interacts with naloxone in inducing pain.
abstract: OBJECTIVE
  Role of nitric oxide (NO) in reversing morphine anti-nociception has been shown. However, the interaction between NO and naloxone-induced pain in the hippocampus is unknown. The present study aimed to investigate the involvement of molecule NO in naloxone-induced pain and its possible interaction with naloxone into cortical area 1 (CA1) of hippocampus.
  
  
  METHODS
  Male Wistar rats (250-350 g), provided by Pasteur Institute of Iran, were housed two per cage with food and water ad libitum. The animals' skulls were cannulated bilaterally at coordinates adjusted for CA1 of hippocampus (AP: -3.8; L: ±1.8- 2.2: V: 3) by using stereotaxic apparatus. Each experimental group included 6-8 rats. To induce inflammation pain, the rats received subcutaneous (s.c.) injections of formalin (50 μL at 2.5%) once prior to testing. To evaluate the nociceptive effect of naloxone, the main narcotic antagonist of morphine (0.1-0.4 mg/kg) was injected intraperitoneally (i.p.) 10 min before injection of formalin. Injections of L-arginine, a precursor of NO, and N(G)-Nitro-L-arginine Methyl Ester (L-NAME), an inhibitor of NO synthase (NOS), intra-CA1, were conducted orderly prior to the administration of naloxone. The pain induction was analyzed by analysis of variance (ANOVA).
  
  
  RESULTS
  Naloxone at the lower doses caused a significant (P<0.01) pain in the naloxone-treated animals. However, pre-administration (1-2 min) of L-arginine (0.04, 0.08, 0.15, 0.3, 1.0, and 3.0 μg/rat, intra-CA1) reversed the response to naloxone. But, the response to L-arginine was blocked by pre-microinjection (1-2 min) of L-NAME (0.15, 0.3, 1.0, and 3.0 μg/rat), whilst, L-arginine or L-NAME alone did not induce pain behavior.
  
  
  CONCLUSIONS
  NO in the rat hippocampal CA1 area is involved in naloxone-induced nociception.
authors.affiliation: Shahed University, Tehran, Iran.
authors.forename: Zahra K
authors.initials: ZK
authors.lastname: Hafeshjani
authors.forename: Manizheh
authors.initials: M
authors.lastname: Karami
authors.forename: Masoomeh
authors.initials: M
authors.lastname: Biglarnia
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D008845:Microinjections / Q000379:methods; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009270:Naloxone / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced* / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D051381:Rats; D017208:Rats, Wistar
chemical_list: D009569:Nitric Oxide; D009270:Naloxone; D019331:NG-Nitroarginine Methyl Ester
keywords: Formalin test; naloxone; nitric oxide; pain