Lack of evidence for significant neuronal loss in laminae I–III of the spinal dorsal horn of the rat in the chronic constriction injury model

Abstract

Peripheral nerve injury leads to structural and functional changes in the spinal dorsal horn, and these are thought to be involved in the development of neuropathic pain. In the chronic constriction injury (CCI) model, abnormal ‘dark’ neurons and apoptotic nuclei have been observed in laminae I–III of the dorsal horn in the territory innervated by the injured sciatic nerve. These findings have been taken as evidence that there is significant neuronal death in this model, and it has been suggested that loss of inhibition resulting from death of GABAergic inhibitory interneurons contributes to the neuropathic pain. However, loss of neurons from the dorsal horn has not been directly demonstrated in neuropathic models, even though this issue is of considerable importance for our understanding of the mechanisms that underlie neuropathic pain. In this study, we have looked for evidence of neuronal death by using a stereological method (the optical disector) with NeuN-immunostaining, and examining spinal cords of naı̈ve rats, and of rats that had undergone CCI or sham operations. All of the CCI animals showed clear signs of thermal hyperalgesia. However, the numbers of neurons in laminae I–III of the ipsilateral dorsal horn in these animals did not differ significantly from those on the contralateral side, nor from those of sham-operated or naı̈ve animals. These results do not, therefore, support the suggestion that there is significant neuronal death in the dorsal horn in this model.