title: The effects of gabapentin in two animal models of co-morbid anxiety and visceral hypersensitivity.
abstract: Visceral hypersensitivity and an increased response to stress are two of the main symptoms of irritable bowel syndrome. Thus efforts to develop animal models of irritable bowel syndrome have centred on both of these parameters. The anticonvulsant gabapentin, which is widely used as an analgesic agent, also reduces anxiety. No data exists to our knowledge of the effects of gabapentin in animal models of co-morbid exaggerated stress response and visceral pain. Our aim was to assess the effect of gabapentin on stress and visceral hypersensitivity in two different animal models of irritable bowel syndrome. The animal models employed were the genetically susceptible Wistar Kyoto rat and the neonatally stressed maternal separation model. These animals were subjected to the open field paradigm to assess stress-induced defecation rates and colorectal distension to assess the level of visceral sensitivity. Gabapentin (30 mg/kg) prevented the stress-induced increase in faecal pellet output in the maternally separated rat, but not the Wistar Kyoto animals. On the other hand gabapentin (30 mg/kg) reduced the number of pain behaviours in response to colorectal distension in both models. These results show that whilst both models have similar responses to gabapentin in terms of visceral pain they differ in terms of their physiological response to stress. This indicates that the origin of anxiety and perhaps then visceral hypersensitivity differs in these models. Overall, these data suggest that gabapentin may be a useful treatment in disorders of co-morbid pain and an overactive stress system such as irritable bowel syndrome.
authors.affiliation: Laboratory of Neurogastroenterology, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. somahony@ucc.ie
authors.forename: Siobhain M
authors.initials: SM
authors.lastname: O' Mahony
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Coelho
authors.forename: Patrick
authors.initials: P
authors.lastname: Fitzgerald
authors.forename: Kevin
authors.initials: K
authors.lastname: Lee
authors.forename: Wendy
authors.initials: W
authors.lastname: Winchester
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Dinan
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
mesh_terms: D000588:Amines / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000453:epidemiology; D015897:Comorbidity; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D000077206:Gabapentin; D007420:Intestine, Large / Q000187:drug effects; D008297:Male; D051381:Rats; D059265:Visceral Pain / Q000188:drug therapy* / Q000453:epidemiology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin