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
