title: Colorectal distension-evoked potentials in awake rats: a novel method for studies of visceral sensitivity.
abstract: BACKGROUND
  Quantification of the visceromotor response induced by colorectal distension (CRD) in rodents is commonly used for preclinical studies of visceral pain. The model is well established but does not fully assess the central response to stimulation. The aim of this study was to establish a novel model assessing cerebral evoked potentials (CEPs) in response to CRD in awake rats.
  
  
  METHODS
  Epidural recording electrodes were chronically implanted in the skull of female Sprague-Dawley rats. Colorectal distension-induced CEPs were recorded using either rapid balloon distensions (100 ms, 20-80 mmHg) or electric stimulation (1 ms, 1-4 mA) using stimulation probes placed in the distal colon.
  
  
  RESULTS
  Colorectal distension-induced CEPs were separated in three partly temporally overlapping components consisting of five prominent peaks. Peak latencies at 80 mmHg were (P1, N1) 23 ± 1 and 55 ± 4 ms, (N2, P2a, P2b) 91 ± 3, 143 ± 5 and 174 ± 3 ms, and (P3) 297 ± 3 ms. Amplitudes and latencies were, except for the early component, intensity dependent. Intrarectal administration of lidocaine significantly reduced the amplitude of N2 (by 42 ± 6%, P < 0.001) and P2 (by 34 ± 6%, P < 0.001). Electrically induced CEPs were intensity dependent and had similar topography and latencies as the mechanical evoked potentials (P1: 26 ± 2 ms; N1: 61 ± 1 ms; P2: 84 ± 6 ms; N2: 154 ± 6 ms; P3: 326 ± 10 ms), but there were large variations in amplitudes in between repeated electrical stimulations.
  
  
  CONCLUSIONS
  Colorectal distension-induced CEPs can be recorded reliably in awake rats and may serve as a surrogate marker of colonic sensation and be a useful parameter in studies of visceral sensitivity.
authors.affiliation: Integrative Pharmacology, AstraZeneca R&D, Mölndal, Sweden. leif.hultin@astrazeneca.com
authors.forename: L
authors.initials: L
authors.lastname: Hultin
authors.forename: T D
authors.initials: TD
authors.lastname: Nissen
authors.forename: D
authors.initials: D
authors.lastname: Kakol-Palm
authors.forename: E
authors.initials: E
authors.lastname: Lindström
mesh_terms: D000818:Animals; D001921:Brain / Q000502:physiology*; D003106:Colon / Q000502:physiology*; D003243:Consciousness; D004108:Dilatation, Pathologic; D004558:Electric Stimulation; D005073:Evoked Potentials, Somatosensory / Q000502:physiology*; D005260:Female; D008365:Manometry; D017288:Pain Threshold; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012007:Rectum / Q000502:physiology*; D059265:Visceral Pain / Q000503:physiopathology*