The analgesic effects of the GABA_B receptor agonist, baclofen, in a rodent model of functional dyspepsia

Background The amino acid γ-aminobutyric acid (GABA) is an important modulator of pain but its role in visceral pain syndromes is just beginning to be studied. Our aims were to investigate the effect and mechanism of action of the GABA_B receptor agonist, baclofen, on gastric hypersensitivity in a validated rat model of functional dyspepsia (FD). Methods 10-day-old male rats received 0.2mL of 0.1% iodoacetamide in 2% sucrose daily by oral gavages for 6days. Control group received 2% sucrose. At 8-10weeks rats treated with baclofen (0.3, 1, and 3mgkg^-1 bw) or saline were tested for behavioral and electromyographic (EMG) visceromotor responses; gastric spinal afferent nerve activity to graded gastric distention and Fos protein expression in dorsal horn of spinal cord segments T8-T10 to noxious gastric distention. Key Results Baclofen administration was associated with a significant attenuation of the behavioral and EMG responses (at 1 and 3mgkg^-1) and expression of Fos in T8 and T9 segments in neonatal iodoacetamide sensitized rats. However, baclofen administration did not significantly affect splanchnic nerve activity to gastric distention. Baclofen (3mgkg^-1) also significantly reduced the expression of spinal Fos in response to gastric distention in control rats to a lesser extent than sensitized rats. Conclusions & Inferences Baclofen is effective in attenuating pain associated responses in an experimental model of FD and appears to act by central mechanisms. These results provide a basis for clinical trials of this drug in FD patients.