Induction of non-painful and painful intestinal sensations by hypertonic saline: a new human experimental model

To develop a pain model for chemical stimulation of the human gut.

In a double-blind experimental study 10 subjects with a previously performed sigmoidostomy were randomised to receive injections with either isotonic or hypertonic saline in the colonic mucosa. In the hypertonic experimental arm, 0.1 ml of 0.9%, 2%, 4%, and 6% and 0.2 ml of 2% and 4% saline were given. In the placebo arm, six 0.9% saline injections of the same quantities were given. In a separate experiment 0.8 ml 4% saline was infused into the mucosa by a pump over a period of 2min. The pain intensity was rated on a 0-10 visual analogue scale with 5 as the pain threshold.

The hypertonic saline injections resulted in local as well as referred non-painful and painful sensations in 9 out of the 10 subjects. The evoked sensations were mostly described as a smarting sensation with an intensity of median 1 (range 0-5.6) for 0.1 ml 2% saline to median 2.9 (range 0-6.2) for 0.2 ml 4% saline. Seven subjects reported referred sensations to the abdominal skin. Continuous infusion of 4% saline resulted in a consistent sensory response in all subjects, with a median intensity of 4.1 (range 2.1-8.1). This sensory intensity was reproducible in 70% in a retest experiment after median 7 weeks. In the placebo arm a total of 70 isotonic saline injections only resulted in inconsistent, short-lasting non-painful sensations in three subjects.

The model represents a safe method for direct chemical activation of the sensory endings in the human gut. The model may be used for pharmacological screening of analgesics and for basic investigations in patients suffering from gastrointestinal diseases.