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. 2001 May;48(5):676–682. doi: 10.1136/gut.48.5.676

Effects of octreotide on responses to colorectal distension in the rat

X Su 1, M Burton 1, G Gebhart 1
PMCID: PMC1728284  PMID: 11302968

Abstract

BACKGROUND AND AIMS—It has been suggested that the analgesic effect of the somatostatin analogue octreotide in visceral pain involves peripheral mechanisms. We evaluated the effect of octreotide on responses to noxious colorectal distension in rats.
METHODS—In a behavioural study, pressor and electromyographic responses to colorectal distension were evaluated before and after intravenous or intrathecal administration of octreotide. In pelvic nerve afferent fibre recordings, responses of mechanosensitive fibres innervating the colon to noxious colorectal distension (80 mm Hg, 30 seconds) were tested before and after octreotide.
RESULTS—Octreotide was ineffective in attenuating responses to colorectal distension in either normal or acetic acid inflamed colon when administered intravenously but attenuated responses when given intrathecally. Administration of octreotide over a broad dose range (0.5 µg/kg to 2.4 mg/kg) did not alter responses of afferent fibres to noxious colorectal distension in untreated, or acetic acid or zymosan treated colons.
CONCLUSIONS—In the rat, octreotide has no peripheral (pelvic nerve) modulatory action in visceral nociception. The antinociceptive effect of octreotide in this model of visceral nociception is mediated by an action at central sites.


Keywords: octreotide; colorectal distension; electromyographic responses; afferent fibres; visceral pain; analgesic effect; rat

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Figure 1  .

Figure 1  

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Stimulus-response functions (SRFs) for visceromotor (A) and pressor (B) responses to colorectal distension before (vehicle) and after intravenous administration of octreotide (100 µg) in saline and acetic acid treated rats. The broken line represents the control response to 80 mm Hg distension as 100%. All data are expressed as percentage of maximal control response (mean (SEM)). The basis for n is the number of rats used in constructing each SRF. *Significantly different from control group (ANOVA).

Figure 2  .

Figure 2  

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Stimulus response functions (SRFs) for visceromotor (A) and pressor (B) responses to colorectal distension (CRD) before (vehicle) and after cumulative doses of intrathecal administration of octreotide (5-15 µg) in saline and acetic acid treated rats. The broken line represents the control response to 80 mm Hg distension as 100%. All data are expressed as percentage of control response (mean (SEM)). The basis for n is the number of rats used in constructing each SRF. Intrathecal octreotide dose dependently attenuated the visceromotor (A) and pressor (B) responses to CRD in saline treated rats.

Figure 3  .

Figure 3  

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Effects of cumulative systemic administration of octreotide on responses of pelvic nerve afferent fibres to noxious colorectal distension (CRD) (80 mm Hg, 30 seconds). Examples of lack of effect of octreotide on responses of different Aδ afferent fibres to CRD in uninflamed colon (A) and zymosan inflamed colon (B). Thirty minutes after intracolonic injection of zymosan (25 mg/ml, 2 ml in 30% ethanol), the fibre in (B) was sensitised (response magnitude increased from 679 imp/30s to 897 imp/30s, an increase to 132% of the pre-zymosan control ("C") response). Octreotide was injected intra-arterially in a cumulative dose as indicated by the arrows. Responses of the fibres are illustrated as peristimulus time histograms (one second binwidth); distending pressure (80 mm Hg, 30 seconds every four minutes) is presented below. In (C), the effect of U50,488 (16 mg/kg) is shown for a fibre that had previously received cumulative doses of octreotide (2.4 mg/kg).

Figure 4  .

Figure 4  

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Absence of dose dependent effects of octreotide on responses of individual pelvic nerve afferent fibres to noxious colorectal distension (80 mm Hg, 30 seconds, as percentage of control). Octreotide failed to attenuate responses of pelvic nerve afferent fibres recorded from either untreated or zymosan treated colon.

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