Reversal of visceral and somatic hypersensitivity in a subset of hypersensitive rats by intracolonic lidocaine

Abstract

Chronic abdominal pain is a common gastrointestinal symptom experienced by patients. We have previously shown that IBS patients with visceral hypersensitivity also have evidence of thermal hypersensitivity of the hand and foot that is reversed by rectal lidocaine jelly. We have also recently developed an animal model of chronic visceral and somatic hypersensitivity in rats treated with intracolonic trinitrobenzene sulfonic acid (TNBS). The objective of the current study was to determine the effects of intracolonic lidocaine on visceral/somatic hypersensitivity in TNBS-treated rats. A total of 20 hypersensitive rats received either 20mg intracolonic lidocaine (n=10) or saline jelly (n=10). In comparison to saline jelly, intracolonic lidocaine jelly reduced responses to nociceptive visceral/somatic stimuli in hypersensitive rats. The effects were present within 5-30 min after administration of lidocaine and lasted for 6h. Lidocaine had no effects on recovered rats or control rats that had originally been treated with intracolonic saline instead of TNBS. Local anesthetic blockade of peripheral impulse input from the colon reduces both visceral and somatic hypersensitivity in TNBS-treated rats, similar to results in IBS patients. The results provide further evidence that visceral and secondary somatic hypersensitivity in a subset of TNBS-treated rats reflect central sensitization mechanisms maintained by tonic impulse input from the colon. This study evaluates the reversal of visceral/somatic hypersensitivity in a subset of TNBS-treated rats with intracolonic lidocaine. This animal model may be used in the future to study the mechanisms of local anesthetic agents applied to the gut to reduce visceral pain.

Fig. 1

Bar graph of colon distension pressures in mmHg vs. time course in hypersensitive rats following lidocaine jelly or saline jelly treatment. White bars indicate mean responses in 10 hypersensitive rats that received saline jelly treatment; black bars indicate mean responses of 10 hypersensitive rats that received lidocaine jelly treatment. Error bars are expressed as means ± standard deviation.

Fig. 2

Bar graph of mechanical threshold testing on hind paws in force/g vs. time course in hypersensitive rats following lidocaine jelly or saline jelly treatment. White bars indicate mean responses of 10 hypersensitive rats that received saline jelly treatment; black bars indicate mean responses of 10 hypersensitive rats that received lidocaine jelly treatment. Error bars are expressed as means ± standard deviation.

Fig. 3

Bar graph of thermal sensitivity testing on hind paws shown as latency (s) vs. time course in hypersensitive rats following lidocaine jelly or saline jelly treatment. White bars indicate mean responses of 10 hypersensitive rats that received saline jelly treatment; black bars indicate mean responses of 10 hypersensitive rats that received lidocaine jelly treatment. Error bars are expressed as means ± standard deviation.

Fig. 4

Bar graph of tail flick shown as latency (s) vs. time course following lidocaine jelly or saline jelly treatment. White bars indicate mean responses of 10 hypersensitive rats that received saline jelly treatment; black bars indicate mean responses of 10 hypersensitive rats that received lidocaine jelly treatment. Error bars are expressed as means ± standard deviation.