Effects of Early Life Iron Deficiency on Nociception

Clinical association studies have identified early life iron deficiency (ID) as a risk factor for the development of chronic pain associated with fibromyalgia and restless legs syndrome. While preclinical studies have shown that early life ID persistently alters neuronal function in the CNS, a causal relationship between early life ID and chronic pain has yet to be established. We sought to address this gap in knowledge by characterizing pain sensitivity in adult mice that were exposed to dietary ID during early development. Dietary iron was reduced by ∼90% in dams between gestational day 14 and postnatal day 10, with dams fed an ingredient matched, iron sufficient diet serving as controls. We then tracked iron status in the offspring during development using a ferrozine based colorimetric assay. To test whether our early life ID model alters adult pain sensitivity following iron repletion, we conducted reflexive behavioral assays of mechanical and thermal pain. No significant difference in mechanical sensitivity was observed between early life ID and control groups of either sex using the von Frey test. Withdrawal latencies to noxious heat or cold, measured with the Hargreaves test and Cold Plantar Assay, were also similar between groups. Collectively, these results suggest that early life ID fails to persistently influence mechanical and thermal pain sensitivity into adulthood. Ongoing studies will determine whether early life ID influences the affective and motivational components of pain or the generation of chronic pain following tissue damage. Grant support from NS080889.