Pathophysiological mechanisms of central neuropathic pain after spinal cord injury.

Abstract

After spinal cord injury (SCI), between 10% and 20% of the patients may develop central neuropathic pain. This type of chronic pain usually is a very bothersome sequel and represents a major therapeutic challenge since conventional medical and surgical pain therapies generally are ineffective. This review focuses on recent advances in the understanding of the pathophysiology of this pain syndrome. Important clinical features of central neuropathic pain after SCI include loss of sensations mediated by spinothalamic pathways combined with development of abnormal pain perception (spontaneous continuous pain and abnormally evoked pain). Up-regulation of neuronal activity leading to spontaneous and evoked neuronal hyperactivity/hyperexcitability, may be the neurophysiological substrate for development of abnormal pain perception. This paper describes some neurochemical changes that may be important for the induction and maintenance of neuronal hyperactivity and abnormal pain perception: Increased excitatory glutaminergic activity involving N-methyl-D-aspartate (NMDA) receptor activation, may trigger the intracellular cascade reaction leading to upregulation of neuronal activity/excitability. Changes in voltage-sensitive Na+ channels may contribute to changes in nerve membrane excitability. Other important mechanisms may be loss of endogenous inhibition, including reduced gamma-amino-butyric acid (GABA)ergic, opioid and monoaminergic inhibition. These various mechanisms may provide new targets for treatment of a pain syndrome that traditionally has been so difficult to handle.