The ontogeny of neuropathic pain: postnatal onset of mechanical allodynia in rat spared nerve injury (SNI) and chronic constriction injury (CCI) models

Abstract

Neuropathic pain is known to occur in children but remains poorly understood and treated. The aim here was to establish a model of neuropathic pain in neonatal and young rodents. In the adult the spared nerve injury (SNI) model produced robust mechanical allodynia measured as a fall in cutaneous sensory threshold to 16% of controls, within one postoperative day and lasting at least 28 days. In contrast, animals aged 3, 10 and 21 days at the time of surgery did not display equivalent allodynia at any time up to 28 days later. A small, transient bilateral increased cutaneous sensitivity was observed at day 7 in P10 and P21 animals but this had gone by 14 days. SNI performed at 33 days led to a significant and persistent allodynia with the threshold falling to 55% of control values. A similar lack of neuropathic pain behaviour in younger animals was observed using the chronic constriction injury (CCI) model, which produced a clear allodynia in adult rats but no change in hindpaw sensitivity when performed at 10 days of age. Mechanical allodynia can be evoked in very young animals with inflammatory pain, so this developmental profile is selective for peripheral neuropathic pain and suggests a remarkable ability in young animals to compensate for the sensory consequences of nerve injury. The results are consistent with human neonatal responses to nerve injury; further study of underlying mechanisms are likely to yield important information about the pathogenesis and treatment of neuropathic pain.