Early-life stress produces muscle hyperalgesia and nociceptor sensitization in the adult rat

Chronic pain in adults has been associated with early-life stress. To examine the pronociceptive effect of early-life stress, we evaluated cutaneous and muscle nociception and activity in muscle nociceptors in an animal model of neonatal stress, limited bedding, in the rat. In this neonatal limited bedding (NLB) model, litters are exposed to limited bedding between postnatal days 2 and 9, and controls to standard bedding. In adult NLB-treated rats, mechanical nociceptive threshold in skeletal muscle was significantly lower (similar to 22%) than in controls. Furthermore, administration of prostaglandin E-2 in skin as well as muscle produced markedly prolonged hyperalgesia, an effect prevented by spinal intrathecal injection of oligode-oxynucleotide antisense to protein kinase C epsilon (PKC epsilon), a second messenger in nociceptors that has been implicated in the induction and maintenance of chronic pain. In electrophysiological studies, mechanical threshold of muscle nociceptors was reduced by similar to 31% and conduction velocity significantly increased (similar to 28%). These findings indicate that neonatal stress induces a persistent hyperalgesia and nociceptor sensitization manifest in the adult and that the second messenger PKCe may be a target against which therapies might be directed to treat a chronic pain syndrome that is associated with early-life traumatic stress. (C) 2011 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.