The Gate Theory of Pain Revisited: Modeling Different Pain Conditions with a Parsimonious Neurocomputational Model.

The gate control theory of pain proposed by Melzack and Wall in 1965 is revisited through two mechanisms of neuronal regulation: NMDA synaptic plasticity and intrinsic plasticity. The Melzack and Wall circuit was slightly modified by using strictly excitatory nociceptive afferents (in the original arrangement, nociceptive afferents were considered excitatory when they project to central transmission neurons and inhibitory when projecting to substantia gelatinosa). The results of our neurocomputational model are consistent with biological ones in that nociceptive signals are blocked on their way to the brain every time a tactile stimulus is given at the same locus where the pain was produced. In the computational model, the whole set of parameters, independently of their initialization, always converge to the correct values to allow the correct computation of the circuit. To test the model, other painful conditions were analyzed: phantom limb pain, wind-up and wind-down pain, breakthrough pain, and demyelinating syndromes like Guillain-Barré and multiple sclerosis.