Figure 6.

Proposed series of events that result in the maintenance of chronic NP. After nerve injury, excess activity within primary afferent neurons results in excessive neurotransmitter release at the primary afferent synapse. This release results in neural death and elicits astrocyte activation, which results in more regular and increased magnitude calcium waves resulting in increased regional homogeneity (RH). This in turn results in oscillatory gliotransmitter release and increased infra-slow neural oscillations, which are subsequently transferred to the somatosensory thalamus. Additional neural loss in the somatosensory thalamus results in reduced blood flow in the TRN and a subsequent reduction in GABAergic release back onto the somatosensory thalamus. This reduced inhibition combined with increased infra-slow oscillations and the recurrent nature of thalamocortical circuits results in altered thalamocortical connectivity, increased dominance of the ascending pain pathway in overall brain function represented by increased degree centrality (DC), altered thalamocortical loop dynamics, a self-sustaining thalamocortical dysrhythmia, and the constant perception of pain.