Effects of tegaserod on Fos, substance P and calcitonin gene-related peptide expression induced by colon inflammation in lumbarsacral spinal cord

Abstract

Aim: To investigate the mechanisms of tegaserod, a partial 5-HT4 agonist, in reducing visceral sensitivity by observing Fos, substance P (SP) and calcitonin gene-related peptide (CGRP) expression in the lumbarsacral spinal cord induced by colonic inflammation in rats.

Methods: Twenty-four male rats with colonic inflammation induced by intraluminal instillation of trinitrobenzenesulfonic acid (TNBS) were divided into 3 groups. Treatment group 1: intra-gastric administration of tegaserod, 2 mg/kg.d; Treatment group 2: intra-gastric administration of tegaserod, 1 mg/kg.d;

Control group: intra-gastric administration of saline, 2.0 mL/d. After 7 d of intra-gastric administration, lumbarsacral spinal cord was removed and processed for Fos, SP and CGRP immunohistochemistry.

Results: In rats of the control group, the majority of Fos labeled neurons was localized in deeper laminae of the lumbarsacral spinal cord (L(5)-S(1)). SP and CGRP were primarily expressed in the superficial laminae of the spinal cord after TNBS injection. Intra-gastric administration of tegaserod (2 mg/kg.d) resulted in a significant decrease of Fos labeled neurons (22.0+/-7.7) and SP density (12.5+/-1.4) in the dorsal horn in the lumbarsacral spinal cord compared to those of the control group (62.2+/-18.9, 35.9+/-8.9, P<0.05). However, CGRP content in dorsal horn did not significantly reduce in rats of treatment group 1 (1.2+/-1.1) compared to that of the control group (2.8+/-2.4, P>0.05). Neither Fos expression nor SP or CGRP density in the dorsal horn significantly declined in rats of treatment group 2 compared to those of the control group (P>0.05).

Conclusion: Tegaserod can significantly reduce Fos labeled neurons in the lumbarsacral spinal cord induced by colonic inflammation. Tegaserod may reduce visceral sensitivity by inhibiting SP expression in the dorsal horn of spinal cord.

Figure 1

Sections from the control rats. ×10. A: Fos-IR neurons induced by TNBS administration were observed as black spots in the dorsal horn. Note that most Fos-IR neurons were distributed in the deeper laminae of the dorsal horn. B: SP was mainly distributed in the superficial laminae of the dorsal horn. C: CGRP was primarily localized in the superficial laminae of the dorsal horn.

Figure 2

Sections from rats treated with tegaserod 2 mg/kg·d. ×10. A: After treatment with tegaserod, the number of Fos-IR cells was decreased significantly compared with that of the control group. B: Note that the density of SP in rats treated with tegaserod was decreased significantly compared with that of the control rats. C: The density of CGRP was not different between the treatment group and the control group.