title: Gabapentin-induced pharmacodynamic effects in the spinal nerve ligation model of neuropathic pain.
abstract: BACKGROUND
  The function of brain networks can be changed in a maladaptive manner in response to chronic neuropathic pain. Analgesics can reduce pain by acting on such networks via direct or indirect (peripheral or spinal) mechanisms. This investigation aimed to map gabapentin's pharmacodynamics (PD) in the rodent brain following induction of neuropathic pain in order to further understand its PD profile.
  
  
  METHODS
  Pharmacological magnetic resonance imaging (phMRI) and a novel functional connectivity analysis procedure were performed following vehicle or gabapentin treatment in the rat spinal nerve ligation (SNL) model of neuropathic pain as well as sham animals.
  
  
  RESULTS
  phMRI performed in SNL animals revealed robust gabapentin-induced responses throughout the hippocampal formation, yet significant (p < 0.05, corrected for multiple comparisons) responses were also measured in other limbic structures and the sensorimotor system. In comparison, sham animals displayed weaker and less widespread phMRI signal changes subsequent to gabapentin treatment. Next, communities of networks possessing strong functional connectivity were elucidated in vehicle-treated SNL and sham animals. We observed that SNL and sham animals possessed distinct functional connectivity signatures. When measuring how gabapentin altered the behaviour of the discovered networks, a decrease in functional connectivity driven by gabapentin was not only observed, but the magnitude of this PD effect was greater in SNL animals.
  
  
  CONCLUSIONS
  Using phMRI and functional connectivity analysis approaches, the PD effects of gabapentin in a preclinical neuropathic pain state were characterized. Furthermore, the current results offer insights on which brain systems gabapentin directly or indirectly acts upon.
authors.affiliation: Integrated Science and Technology, Abbvie Inc., North Chicago, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Hooker
authors.forename: G
authors.initials: G
authors.lastname: Tobon
authors.forename: S J
authors.initials: SJ
authors.lastname: Baker
authors.forename: C
authors.initials: C
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Hesterman
authors.forename: K
authors.initials: K
authors.lastname: Schmidt
authors.forename: R
authors.initials: R
authors.lastname: Rajagovindan
authors.forename: P
authors.initials: P
authors.lastname: Chandran
authors.forename: S K
authors.initials: SK
authors.lastname: Joshi
authors.forename: A W
authors.initials: AW
authors.lastname: Bannon
authors.forename: J
authors.initials: J
authors.lastname: Hoppin
authors.forename: J
authors.initials: J
authors.lastname: Beaver
authors.forename: G B
authors.initials: GB
authors.lastname: Fox
authors.forename: M
authors.initials: M
authors.lastname: Day
authors.forename: J
authors.initials: J
authors.lastname: Upadhyay
mesh_terms: D000588:Amines / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D000077206:Gabapentin; D008297:Male; D009437:Neuralgia / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013127:Spinal Nerves / Q000187:drug effects* / Q000503:physiopathology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin