Stress induced Visceral Hypersensitivity: Modulation by preceding mucosal Inflammation and role of Neurokinin Receptors

Aims: Altered processing of visceral afferent information is believed to play a key role for the manifestation of patients in at least a subgroup of patients with functional gastrointestinal disorders. However, underlying mechanisms are poorly understood, while it is well recognized that there are initiating events such as mucosal inflammation and stress that obviously precipitate the onset of symptoms.

Aims: We aimed to study the role of mucosal inflammation and a repeated standardized stressor on visceral sensory function and the link to Neurokinin (NK) receptor expression.

Methods : In randomized order, trinitrobenzene sulphonic acid (TNBS) or saline were instilled into the colorectum of female Lewis rats (n=80). Colorectal distensions (CRD) were performed with a barostat device (3min/40mmHg) and to quantify the visceromotor response to CRD the electromyographic activity (EMG) of the abdominal muscles was recorded. In randomized order equal numbers of both treatment group underwent either seven days (1h/day) repetitive water avoidance (WA) stress or were allowed to recover under resting conditions. CRD were conducted 14 days later. Colonic tissue samples were taken 2 weeks after induction of inflammation and the presence of messenger RNA for NK1, NK2 and NK3 receptors were identified by rtPCR.

Results: Compared to controls, water avoidance significantly augmented the visceromotor response (VMR) to CRD by 430.2%±3.2% (p<0.001) whereas the response was diminished after TNBS plus WA (197.5%±4.2%). TNBS alone did not significantly alter the VMR. However, TNBS alone significantly reduced NK1 (–37.2±6,1%) and NK3 (–25,5±4,9%) receptor expression compared to saline controls. WA alone did not significantly influence NK1, NK2 and NK3 receptor expression.

Conclusions: An acute mucosal inflammation has profound effects on NK receptor expression that reflects an adaptive response to the noxious stimulus. Concomitant WA stress attenuates the adaptive response of NK receptors. Disturbed adaptation of NK expression after stress may explain the influence of psychological factors on postinflammatory visceral hyperalgesia.

Key words

colorectal distension - inflammation - stress - visceral hyperalgesia