Pain-Related Motor Cortex Disinhibition in Patients with Neuralgia after Peripheral Nerve Lesion – A Transcranial Magnetic Stimulation (TMS) Study

Different studies have suggested a relationship between chronic pain and reorganization in the human sensorimotor cortex, e.g., in patients with limb amputation or complex regional pain syndrome (CRPS). Cortical reorganization might be based on changes of synaptic efficacy requiring a reduction of GABAergic inhibition and an activation of NMDA receptors and, therefore, be linked to changes of cortical excitability. Such cortical excitability changes might be reflected by changes of intracortical inhibition (ICI) and facilitation (ICF) as assessed by paired pulse TMS. The aim of the present study was to assess such possible changes of ICI and ICF in patients with neuralgia after incomplete peripheral nerve lesion, and its relationship to the intensity of neuropathic pain. In 19 patients with neuralgia after incomplete unilateral lesion of the median or ulnar nerve, ICI and ICF were assessed by paired pulse TMS according to the paradigm described by Kujirai et al. (1993). Recordings were taken from the abductor pollicis brevis and the abductor digiti minimi muscles of both hands. Results from the muscle supplied by the lesioned nerve were considered separately from results from the muscle supplied by the unlesioned nerve of the affected hand. Both were compared to results from the corresponding muscles of the unaffected hand. There was a significantly reduced ICI (i.e., higher relative amplitudes) in the hemisphere contralateral to the nerve lesion as revealed by recordings from the muscle supplied by the lesioned nerve (mean relative amplitude 85.1±78.7% vs. 44.1±28.5%; p<0.05) and by recordings from the muscle supplied by the unlesioned nerve (mean relative amplitude 57.9±35.4% vs. 37.1±16.8%; p<0.05). ICF did not differ significantly between the two hemispheres. The amount of disinhibition correlated positively with the pain intensity as assessed by a numeric rating scale (r=0.577, p<0.05). We conclude that in patients with neuralgia after incomplete peripheral nerve lesion there exists a unilateral disinhibition of the corresponding motor cortex, which is related to pain intensity. This finding suggests a relationship between cortical excitability changes, cortical reorganization and chronic neuropathic pain in these patients. The results contrast with the bilateral motor cortex disinhibition in CRPS patients. This points to important pathophysiological differences between CRPS and neuralgia, and might have a future diagnostic and therapeutic impact.