Neonatal inflammation and primary afferent terminal plasticity in the rat dorsal horn

Abnormal or excessive activity related to pain and injury in early life may alter normal synaptic development and lead to changes in somatosensory processing. The aim of the current study was to define the critical factors that determine long-term plasticity in spinal cord afferent terminals following neonatal inflammation. Hindpaw inflammation was produced in neonatal rat pups with 5 or 25 mul 2% carrageenan, and 5 or 25 mul complete Freund's adjuvant (CFA). All groups displayed a clear inflammatory response that recovered in 2 weeks in all but the 25 p] CFA group, who had persistent chronic inflammation confirmed by histological examination of the paw at 8 weeks. The 25 mul CFA group was also the only group that displayed a significant expansion of the sciatic and saphenous nerve terminal field in lamina II of the dorsal horn at 8 weeks, using wheat-germ agglutinin-horse radish peroxidase transganglionic labelling. This effect was not accompanied by changes in dorsal root ganglion (DRG) cell number, expression of activating transcription factor 3 (ATF3), or alterations in calcitonin gene related peptide (CGRP) or isolectin 134 binding; and was not mimicked by partial nerve damage. No long-term change in mechanical or thermal behavioural sensory thresholds was seen in any group. Lower dose CFA caused an acute, reversible expansion of terminal fields in lamina II in neonatal animals, while CFA did not produce this effect in adults. The duration and effect of neonatal inflammation is therefore dependent on the type and volume of inflammatory agent used. The expansion of afferent terminals in lamina II following neonatal CFA inflammation is maintained into adulthood if the inflammation is also maintained, as seen following 25 mul CFA. This effect is not seen in adult animals, emphasising the plasticity of the nervous system early in development. (C) 2003 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.