THE DEVELOPMENT OF SPINAL CORD CIRCUITS UNDERLYING WIDESPREAD NOCICEPTIVE BEHAVIOURS

Chronic widespread pain is characterised by a failure to spatially restrict nociceptive responses, leading to pain and reflex recruitment across multiple body regions. Strikingly, this behavioural phenotype resembles pain responses early in postnatal development, when immature spinal circuits generate exaggerated, whole-body nocifensive reflexes that later become spatially refined. This parallel suggests that widespread pain may reflect dysregulation of developmentally transient spinal pathways. Here, we investigate the developmental organisation of Tac1-expressing lumbo-cervical propriospinal neurons (Tac1 PPNs), a spinal population anatomically positioned to distribute nociceptive signals across segments. Using Tac1-Cre mice, we quantified the maturation of spreading nociceptive reflexes evoked by focal laser stimulation across postnatal development, alongside anatomical mapping of Tac1 PPN projections. Behavioural analyses show that spreading reflex recruitment persists into late postnatal life before becoming spatially restricted in adulthood. In parallel, anatomical labelling reveals progressive postnatal maturation across postnatal ages. Together, these findings support a model in which immature Tac1-associated propriospinal connectivity enables diffuse nocifensive responses early in life, and that disruption of this refinement process may contribute to pathological spreading pain. Ongoing work tests whether Tac1 PPN activity is sufficient to recruit spreading reflexes in the absence of injury and whether these circuits become dysregulated in models of widespread pain. Defining the developmental logic of spinal pain distribution circuits provides a framework for understanding mechanisms of widespread pain and identifying circuit-level targets for therapeutic intervention.