The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury.
Vega-Avelaira D, McKelvey R, Hathway G, Fitzgerald M.
Mol Pain. 2012 Apr 24;8(1):30. [Epub ahead of print]ABSTRACT:
Abstract
BACKGROUND: Peripheral nerve injuries can trigger neuropathic pain in adults but cause little or no pain when they are sustained in infancy or early childhood. This is confirmed in rodent models where neonatal nerve injury causes no pain behaviour. However, delayed pain can arise in man some considerable time after nerve damage and to examine this we have carried out a longer term follow up of rat pain behaviour into adolescence and adulthood, following early life nerve injury. RESULTS: Spared nerve injury (SNI) or sham surgery was performed on 10 day old (P10) rat pups and mechanical nociceptive reflex thresholds were measured 3, 7, 14, 21, 28, 38 and 44 days post surgery. While mechanical thresholds on the ipsilateral side are not significantly different from controls for the first 2-3 weeks post P10 surgery, after that time, beginning at 21 days post surgery (P31), the SNI group developed significant hypersensitivity compared to the other groups. Ipsilateral mechanical nociceptive thresholds were 2-fold lower than the contralateral and sham thresholds, 21 days post surgery (SNI-ipsilateral 28 (+/-5) g control groups 69 (+/-9) g, p<0.001, 3-way ANOVA, n=6 per group). Importantly, no effect was observed on thermal thresholds. This hypersensivity was accompanied by macrophage, microglial and astrocyte activation in the DRG and dorsal horn, but no significant change in dorsal horn p38 or JNK expression. Preemptive minocycline (daily 40mg/kg, s.c) did not prevent the effect. Ketamine (1-20mg/kg, s.c), on the other hand, produced a dose-dependent reversal of mechanical nociceptive thresholds ipsilateral to the nerve injury and thresholds returned to control levels at the highest doses. CONCLUSIONS: We report a novel consequence of early life nerve injury whereby mechanical hypersensitivity only emerges later in life. This delayed adolescent onset in mechanical pain thresholds is accompanied by neuroimmune activation and NMDA dependent central sensitization of spinal nociceptive circuits. This delayed onset in mechanical pain sensitivity may provide clues to understanding the long term effects of early injury such as late onset phantom pain and the emergence of complex adolescent chronic pain syndromes.
|
No hay comentarios:
Publicar un comentario