Activation of
GABA(B) receptors by the selective agonist
baclofen produces anti-nociceptive effects in animal models of
somatic pain. The aim of the present study was to evaluate the effect of
baclofen and the
GABA(B) receptor positive allosteric modulator
CGP7930 on pseudo-affective responses to colorectal distension in rats. Female Sprague-Dawley rats were subjected to repeated, noxious colorectal distension (CRD) (12 distensions at 80 mmHg, for 30 s with 5 min intervals). The visceromotor response (VMR) and cardiovascular responses (mean arterial blood pressure (ABP) and heart rate (HR)) to CRD were monitored in conscious, telemetrized animals.
Baclofen (0.3-3 micromol/kg, i.v.) reduced the VMR to CRD dose-dependently, reaching a 61% maximal inhibition (p < 0.001). The highest doses of
baclofen attenuated CRD-evoked increases in ABP by 17% (p > 0.05) and reduced the change in HR by 48% (p < 0.01).
CGP7930 (3-30 micromol/kg, i.v.) reduced the VMR to CRD in a dose-dependent fashion with a maximal inhibition of 31% (p < 0.05). The highest dose of
CGP7930 also attenuated the increase in ABP by 18% (p > 0.05) and inhibited the increase in HR by 24% (p < 0.05) associated with CRD. Neither
baclofen nor
CGP7930 affected colorectal compliance. The results suggest that activation of
GABA(B) receptors produces anti-nociceptive effects in a rat model of mechanically induced
visceral pain. While
CGP7930 was less efficacious than
baclofen overall, positive allosteric modulation of
GABA(B) receptors may represent a valid approach in the treatment of
visceral pain conditions, with the possibility of an improved safety profile compared to full agonism.