Original Report| Volume 14, ISSUE 10, P1173-1184, October 2013

Maternal Deprivation Is Associated With Sex-Dependent Alterations in Nociceptive Behavior and Neuroinflammatory Mediators in the Rat Following Peripheral Nerve Injury

  • Nikita N. Burke
    Physiology, School of Medicine, NCBES Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland, Galway, Ireland
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  • Ricardo Llorente
    Departamento de Fisiología (Fisiología Animal II), Facultad de Ciencias Biológicas, Universidad Complutense de Madrid & Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
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  • Eva M. Marco
    Departamento de Fisiología (Fisiología Animal II), Facultad de Ciencias Biológicas, Universidad Complutense de Madrid & Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
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  • Kezanne Tong
    Physiology, School of Medicine, NCBES Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland, Galway, Ireland
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  • David P. Finn
    Pharmacology and Therapeutics, School of Medicine, NCBES Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland, Galway, Ireland
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  • Maria-Paz Viveros
    Departamento de Fisiología (Fisiología Animal II), Facultad de Ciencias Biológicas, Universidad Complutense de Madrid & Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain
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  • Michelle Roche
    Address reprint requests to Michelle Roche, PhD, Physiology, School of Medicine, National University of Ireland, Galway, University Road, Galway, Ireland.
    Physiology, School of Medicine, NCBES Centre for Pain Research and Galway Neuroscience Centre, National University of Ireland, Galway, Ireland
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      Early-life stress is associated with an increased risk of developing affective disorders and chronic pain conditions. This study examined the effect of maternal deprivation (MD) on nociceptive responding prior to and following peripheral nerve injury (L5-L6 spinal nerve ligation [SNL]). Because neuroimmune signaling plays an important role in pain and affective disorders, associated alterations in glial and cytokine expression were assessed in key brain regions associated with emotional and nociceptive responding, the hippocampus and prefrontal cortex. MD female, but not male, rats exhibited thermal hypoalgesia and mechanical allodynia compared with control (non-MD) counterparts. SNL resulted in mechanical and cold allodynia in MD and control rats of both sexes. However, MD females exhibited enhanced SNL-induced allodynic responding compared with non-MD counterparts. Interleukin 6 (IL-6) expression was reduced in the prefrontal cortex of MD-SNL males when compared with non-SNL counterparts. Glial fibrillary acidic protein and IL-1β expression in the hippocampus of MD-SNL males was increased compared with non-MD controls. MD-SNL females exhibited reduced tumor necrosis factor alpha in the prefrontal cortex with a concomitant increase in IL-6 and tumor necrosis factor alpha expression in the hippocampus, compared with either MD or SNL alone. In conclusion, MD female, but not male, rats exhibit enhanced nociceptive responding following peripheral nerve injury, effects that may relate to the distinct neuroinflammatory profile observed in female versus male rats.


      This study demonstrates that females rats exposed to early-life stress exhibit enhanced neuropathic pain responding, effects that are associated with alterations in neuroinflammatory mediators. Increased understanding of the interactions among early-life stress, gender, and pain may lead to the identification of novel therapeutic targets for the treatment of chronic pain disorders.

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