title: Gabapentin evoked changes in functional activity in nociceptive regions in the brain of the anaesthetized rat: an fMRI study.
abstract: OBJECTIVE
  Gabapentin (GBP; 1-(aminomethyl)cyclohexane acetic acid) is used clinically in the treatment of pain. Nevertheless, the sites and mechanisms of action of GBP are poorly defined. Herein, the effects of GBP on brain activation have been studied.
  
  
  METHODS
  Changes in blood oxygen level dependent (BOLD) haemodynamic signal following intravenous infusion of GBP (equivalent to 30 mg kg(-1) p.o., followed by 100 mg kg(-1) p.o.), compared to saline control, were studied in isofluorane anaesthetized rats (n=8 per group). Effects of GBP on mean arterial blood pressure (MAP) were also recorded.
  
  
  RESULTS
  Random effect analysis revealed that the lower dose of GBP produced significant (P<0.001) increases in BOLD signal intensity in several brain regions, including the thalamus and periaqueductal grey (PAG), compared to basal. This dose of GBP also produced significant (P<0.001) decreases in BOLD signal intensity in the amygdala and the entorhinal cortex. Increasing the dose of GBP (100 mg kg(-1)) produced significantly greater changes in BOLD signal intensity in several brain regions including the thalamus and PAG. MAP was not significantly altered by GBP, compared to saline.
  
  
  CONCLUSIONS
  GBP had marked positive and negative effects on BOLD signal intensity in a number of brain regions in naïve rats. The activation of key areas involved in nociceptive processing indicate a supraspinal site of action of GBP and this may contribute to its well-described analgesic effects in animal models of pain and clinical studies.
authors.affiliation: School of Biomedical Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK. rgoverno@fmrib.ox.ac.uk
authors.forename: R J M
authors.initials: RJ
authors.lastname: Governo
authors.forename: P G
authors.initials: PG
authors.lastname: Morris
authors.forename: C A
authors.initials: CA
authors.lastname: Marsden
authors.forename: V
authors.initials: V
authors.lastname: Chapman
mesh_terms: D000284:Administration, Oral; D000588:Amines / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D001931:Brain Mapping / Q000379:methods; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D000077206:Gabapentin; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging / Q000379:methods; D010100:Oxygen / Q000097:blood; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D010100:Oxygen