Figure 7.

Representative Current-Clamp Traces for the Number of Action Potentials at Double Rheobase in Colonic Supernatant Experiments

Current-clamp traces at double rheobase are presented at baseline (black) and following acute morphine challenge (3 μM, red) for naive DRG neurons exposed to colonic supernatants from each treatment cohort. Neurons in supernatants from PP + SAL and PP + VAN mice demonstrated low excitability at baseline, most often characterized by a single action potential at double rheobase. Owing to a floor effect, no reduction could be detected with morphine perfusion. Neurons in supernatants from MP + SAL mice demonstrated enhanced excitability at baseline, characterized by a greater number of action potentials at double rheobase. No reduction was detected with acute morphine challenge, indicating tolerance development. Neurons in supernatants from MP + VAN mice were also hyperexcitable at baseline, but demonstrated a reduction in the number of action potentials at double rheobase with acute morphine challenge, indicating tolerance prevention (see Figure 9 for individual observations).