pregabalin and Dilatation--Pathologic

Cerebral evoked potentials (CEP) induced by colorectal distension (CRD) in conscious rats provides a novel method in studies of visceral sensitivity. The aim of this study was to explore the pharmacological effect on CEP of compounds known to reduce the visceromotor response to CRD.. Epidural electrodes were chronically implanted in eight female Sprague-Dawley rats. Evoked potentials were elicited by colorectal rapid balloon distensions (100 ms, 80 mmHg) and the effect of WIN55 (cannabinoid CB receptor agonist), clonidine (adrenergic α. WIN55 (0.1 μmol kg. The obtained results suggest that MPEP, WIN55, clonidine, and pregabalin reduce visceral nociceptive input to the brain, whereas the lack of effect of baclofen on CRD evoked CEP amplitudes suggest that the effect on VMR is not due to a direct analgesic effect. Brain responses to colorectal distension provide a useful tool to evaluate pharmacological effects in rats and may serve as a valuable preclinical model for understanding pharmacological mechanisms related to visceral sensitivity.

Topics: Animals; Baclofen; Benzoxazines; Cerebral Cortex; Clonidine; Colon; Dilatation, Pathologic; Evoked Potentials; Female; Morpholines; Naphthalenes; Pregabalin; Pyridines; Rats

Pregabalin, which binds to the alpha2-delta subunit of voltage-gated calcium channels, increased the threshold for pain during colorectal distension (CRD) in irritable bowel syndrome (IBS) patients. We tested the effects of oral pregabalin on the visceral pain-related viscerosomatic and autonomic cardiovascular responses to CRD and colonic compliance in rats.. The activity of the abdominal musculature (viscerosomatic response), monitored by electromyography and intracolonic manometry, and changes in blood pressure and heart rate, monitored by telemetry, were assessed simultaneously in conscious rats during CRD.. Pregabalin (10-200 micromol kg(-1), p.o.) inhibited dose dependently the viscerosomatic response to phasic, noxious CRD (12 distensions at 80 mm Hg). At 200 mumol kg(-1), pregabalin also reduced the increase in blood pressure and heart rate associated with noxious CRD. Moreover, pregabalin (200 micromol kg(-1), p.o.) reduced the visceromotor response to ascending phasic CRD (10-80 mm Hg) and significantly increased the threshold pressure for response. During phasic CRD (2-20 mm Hg), pregabalin (200 micromol kg(-1), p.o.) increased intracolonic volume, resulting in a shift to the left of the pressure-volume relationship curve, indicative of an increase of compliance.. Pregabalin reduced the viscerosomatic and autonomic responses associated with CRD-induced visceral pain and increased colonic compliance in rats. These observations confirm the analgesic activity of pregabalin on visceral pain and support the translational value of the CRD model to humans. Ligands for the alpha2-delta subunit might represent interesting compounds for the treatment of visceral pain disorders, such as IBS.

Topics: Abdominal Pain; Administration, Oral; Analgesics; Animals; Blood Pressure; Calcium Channels; Colon; Compliance; Dilatation, Pathologic; Disease Models, Animal; Dose-Response Relationship, Drug; Female; gamma-Aminobutyric Acid; Heart Rate; Irritable Bowel Syndrome; Manometry; Pregabalin; Protein Subunits; Rats; Rats, Sprague-Dawley