Chronic pain secondary to neuronal injury is actively and continuously modulated at multiple locations along the sensory neuraxis. Here, we describe how nociceptive neurons of the spinal cord and thalamus process and communicate nociceptive information in terms of precisely calibrated firing patterns. We then discuss how several cell types with immunogenic properties (e.g. blood cells and glia) cause system-wide interference in nociceptive processing through novel signaling schema, thus contributing to nociceptive network plasticity and chronic pain.