Z Gastroenterol 2005; 43 - P128
DOI: 10.1055/s-2005-919902

Role of Central Kappa Opioid Receptors in Post-inflammatory Visceral Hyperalgesia

B Adam 1, T Liebregts 1, A Bertel 1, G Holtmann 1
  • 1Dept of Gastroenterology, Hepatology and General Medicine, Royal Adelaide Hospital, University of Adelaide, Australien, Adelaide, Australien

Aims: Visceral hyperalgesia following an acute mucosal inflammation is believed to play a key role for a subset of patients with functional gastrointestinal disorders. The influence of opioidergic pathways for disturbances of visceral function has been partially characterized in human and animal studies. Data on the persistence of functional abnormalities of the opioidergic system following an acute mucosal inflammation are lacking.

Aims: (1) To evaluate the effect of the kappa opioid agonist (KOA) U50488H on visceral sensory function and (2) to determine changes of peripheral and central opioid receptor expression following a transient colonic inflammation.

Methods: Pressure controlled colorectal distensions (CRD) (40 mmHg) were performed in male Lewis rats 4 weeks after colorectal instillation of TNBS (test group) or saline (controls) consisting of 3 phasic CRD's before (baseline) and 3 phasic CRD's 1, 2 and 5 min after intraperitoneally (i.p.) injection of 100nmM of KOA or 0.9% saline in control experiments. The visceromotor response (VMR) to CRD was registered by recording electromyographic activity of the abdominal wall musculature. To assess alterations of central and peripheral kappa opioid receptor mRNA expression colonic and brainstem tissue samples of TNBS and saline treated rats were analyzed by a semi-quantitative reverse transcription- polymerase chain reaction.

Results: 4 weeks after TNBS instillation the VMR to CRD was significantly increased compared to saline controls. I.p. injection of saline did not alter the VMR. In controls, U50488H decreased the VMR by –53.1%±7.9% 5 min after injection compared to baseline level. In contrast, a reduction of the VMR of only –19%±3.2% was observed in the TNBS group. Opioid receptor expression in the brainstem was significantly increased by 51.5% in TNBS treated rats. In the colonic tissue samples there was no significant difference between TNBS treated and control animals (–94.5%±7.2% vs. –85.4%±7.9%) compared to GAPDH.

Conclusion: The analgesic effect of the kappa opioid agonist U50488 is attenuated in postinflammatory visceral hyperalgesia which might be linked to alterations of central but not peripheral opioid receptor expression.

Keywords: inflammation, kappa opioid receptors, treatment, visceral hyperalgesia