Pain-motor integration in the primary motor cortex in Parkinson's disease

Abstract Background In Parkinson's disease (PD), the influence of chronic pain on motor features has never been investigated. We have recently designed a technique that combines nociceptive system activation by laser stimuli and primary motor cortex (M1) activation through transcranial magnetic stimulation (TMS), in a laser-paired associative stimulation design (Laser-PAS). In controls, Laser-PAS induces long-term changes in motor evoked potentials reflecting M1 long-term potentiation-like plasticity, arising from pain-motor integration. Objective We here examined the possible influence of chronic pain on motor responses to Laser-PAS in patients with PD, with and without chronic pain. Methods We compared motor responses to Laser-PAS in healthy subjects and in patients with PD, with and without chronic pain. Results Unlike controls, we found reduced responses to Laser-PAS in patients with PD, with and without pain. Patients off and on dopaminergic therapy had similar responses to Laser-PAS. When comparing responses to Laser-PAS in patients with and without pain, the two patients' subgroups had similar abnormalities. When we compared patients with pain in the body region investigated with Laser-PAS, with those with pain in other body regions, we found prominent changes in patients with homotopic pain. Finally, when comparing Laser-PAS with the original PAS protocol, which combines electric peripheral nerve stimuli and TMS, in patients without pain and those with homotopic pain, we found similar responses to both techniques in patients without pain, whereas Laser-PAS induced greater abnormalities than PAS in patients with pain. Conclusions In PD, chronic pain degrades response to Laser-PAS through abnormal pain-motor integration.