Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice: spinal cord c-Fos expression and behavior.
During acute and chronic inflammation visceral pain perception is altered. Conflicting data exist, however, on visceral pain perception in the postinflammatory phase. The aim of the present study was to investigate whether visceral pain perception is altered after resolution of dextran sodium sulfate (DSS)-induced inflammation of the colon. Visceral sensory function in mice was assessed by monitoring behavioral responses to intracolonic capsaicin instillation. Two hours later the number of c-Fos-positive neurons in lamina I/II and X of spinal cord segments T(12/13)-S1 was determined as a measure of neuronal activation. DSS colitis was induced by adding 1% of DSS to the drinking water. The course of DSS-induced colitis was assessed by determining the disease activity index score. Animals developed a transient colitis and had recovered at day 49. At this time point, cytokine levels and colon length were similar to control animals. Importantly, after resolution of DSS-induced colitis the behavioral response to intracolonic capsaicin was increased compared with control mice. Moreover, capsaicin-induced spinal cord neuronal c-Fos expression was significantly increased. Interestingly, after colitis animals also exhibited referred somatic hyperalgesia as measured with von Frey hairs on the abdominal wall. We conclude that postinflammatory visceral hyperalgesia occurs after resolution of DSS-induced colitis and that capsaicin-induced behavioral responses and spinal cord neuronal c-Fos activation are effective readouts for determination of visceral pain perception.
Laboratory for Psychoneuroimmunology, Univ. Medical Center Utrecht, Rm. KC 03.063.0, Lundlaan 6, 3584 EA Utrecht, The Netherlands.
Niels
N
Eijkelkamp
Annemieke
A
Kavelaars
Sigrid
S
Elsenbruch
Manfred
M
Schedlowski
Gerald
G
Holtmann
Cobi J
CJ
Heijnen
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology*; D003092:Colitis / Q000139:chemically induced / Q000503:physiopathology*; D003106:Colon; D016264:Dextran Sulfate; D005260:Female; D006930:Hyperalgesia / Q000139:chemically induced; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000139:chemically induced; D017288:Pain Threshold; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D013116:Spinal Cord / Q000378:metabolism*; D050916:TRPV Cation Channels / Q000096:biosynthesis
D016760:Proto-Oncogene Proteins c-fos; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D016264:Dextran Sulfate; D002211:Capsaicin