A combination of peppermint oil and caraway oil attenuates the post-inflammatory visceral hyperalgesia in a rat model

Objective: Visceral hyperalgesia plays a pivotal role in manifestation of symptoms in patients with functional gastrointestinal disorders. In clinical studies combined treatment of peppermint- and caraway oil significantly reduced symptoms. Thus, the aim of this study was to characterize the effects of peppermint- and caraway oil, individually and in combination, on visceral nociception in a rat model of post-inflammatory visceral hyperalgesia. Material and methods: On day 28, male Lewis rats (n=80) were randomized to treatment with a rectal administration of trinitrobenzene sulphonic acid (TNBS)/ethanol or physiological saline solution. To quantify the visceromotor response to a standardized colorectal distension, bipolar electrodes were implanted into the external oblique musculature, just superior to the inguinal ligament for electromyographic recordings on day 3. On day 0, baseline measurement was performed. Thereafter, oral treatment with peppermint- or caraway oil or combination treatment was started and continued for 14 consecutive days. After 7 and 14 days of treatment a colorectal distension was performed. Colonic tissue samples were obtained on days 0, 7 and 14 to assess histological alterations due to the different treatment groups and the influence of different compounds. Results: After a single instillation of TNBS/ethanol persistent elevation of the visceromotor response at all different time-points was observed, although colonic mucosa was completely normal. After 14 days of combined treatment with peppermint- and caraway oil, a reduced visceromotor response of up to 50% compared to placebo was detected in TNBS/ethanol pretreated animals. In contrast, neither peppermint- nor caraway oil had a significant effect on post-inflammatory visceral hyperalgesia. In saline-treated controls there was no significant difference in the visceromotor response. Conclusions: These data show that combined treatment with peppermint- and caraway oil modulates post-inflammatory visceral hyperalgesia synergistically. The exact mechanisms have to be further investigated.Birgit Adam, Tobias Liebregts, Jan Best, Lars Bechmann, Carolin Lackner, Jens Neumann, Stephan Koehlers and Gerald Holtman