Effects of perinatal iron deficiency on spinal dorsal horn circuits.

Abstract

Clinical association studies have identified early life iron deficiency (ID) as a risk factor for the development of chronic pain. ID during the perinatal period has long-term consequences for the developing nervous system. Mounting evidence from both clinical and preclinical studies suggests that ID alters pain perception. However, nothing is yet known about how perinatal ID impacts nociceptive circuitry. The present study sought to characterize the effects of ID on the spinal superficial dorsal horn (SDH). Using ex vivo patch clamp electrophysiology in a mouse model of perinatal ID, the excitability of inhibitory and putative excitatory interneurons in the SDH was measured. It was found that early life ID did not significantly change the intrinsic excitability of either interneuron cell type in adolescence or adulthood. The investigation of synaptic inputs onto these two populations revealed that ID modulates spontaneous glutamatergic transmission within the SDH, but did not affect the excitatory drive or balance of synaptic excitation and inhibition. Interestingly, while ID altered the pattern of primary afferent inputs onto presumed glutamatergic interneurons in the mature SDH, the overall efficacy of these synapses was not affected by ID. Collectively, these results suggest that spinal nociceptive circuits are resilient to change following perinatal ID. PERSPECTIVE: This study demonstrates that perinatal iron deficiency (ID) elicits few changes to the intrinsic membrane excitability of superficial dorsal horn neurons or the efficacy of their synaptic inputs. These findings represent a critical first step towards elucidating the effects of ID on nociceptive processing in the central nervous system.