Although pain is one of the major clinical symptoms of Parkinson's disease (PD) and multiple sclerosis (MS), it is often neglected and therefore undertreated. The question why the perception of pain in stages without cognitive impairment is not affected by the neuropathology has not been addressed so far. Furthermore, changes in the experience of pain as a result of cognitive impairment have not been clinically studied in PD and MS. These issues which are very relevant for pain assessment and treatment, will be addressed by discussing the neuropathology in the medial and lateral pain systems in cognitively intact versus cognitively impaired patients with PD and MS. Since there are no clinical studies that specifically address pain in cognitively impaired PD and MS patients, hypotheses will be generated about the impact of cognitive impairment on pain experience in these patients. These hypotheses should be a challenge for new research in this important but neglected area.