New ion channel pair (CaL+Kir) identified as key driver of chronic pain neuron switching

A new computational study from the University of Liège has uncovered a specific ion channel interaction that may explain how neurons in the spinal cord’s dorsal horn switch into a chronic pain state. The paper, authored by Anaëlle De Worm, Guillaume Drion, and Pierre Sacré and published on arXiv, shows that inward rectifier potassium (Kir) channels combine with voltage-gated L-type calcium (CaL) channels to produce robust, physiological bistability – the ability for a neuron to toggle between a resting state and a spiking plateau. This property is critical during central sensitization, the process that makes pain signals persist long after an injury heals.

Using a minimal conductance-based model, the team compared the CaL+Kir pair against the more well-known CaL+KM (M-type potassium) combination. They found that Kir channels actually enlarge the bistability window, while KM channels shrink it slightly. The CaL+Kir configuration not only produced a much larger bistability region but was also more resilient to noise and intrinsic variability. Mechanistically, this arises because the Kir current possesses a region of negative differential conductance near the spike threshold – a feature absent in KM and most other voltage-gated potassium currents. The results held when tested in a realistic two-compartment model of deep projection neurons, identifying the CaL+Kir pair as a prime candidate intrinsic mechanism for central sensitization.