Purpose: This study aimed to assess the use of neuropsychologic tests as a tool to differentiate, or not, between a nonresponding chronic pain condition of nonmuscular origin, irritable bowel syndrome (IBS) (n = 20), versus 2 pain conditions of muscular origin, responding (n = 36) and nonresponding (n = 24) temporomandibular disorders. Materials and Methods: The neuropsychologic tests used were the simple and multiple-choice reaction-time tests, California Verbal Learning Tests, the Brown-Peterson Consonant Trigram Auditory Memory Test, Sleep Assessment Questionnaire, and Beck Depression Inventory, as well as fatigue and energy level assessments (100-mm visual analog scale). Results: Most of the tests used were capable of significantly differentiating between responding TMD versus IBS patients. Conversely, no statistically significant difference was found between nonresponding TMD versus IBS patients. Overall, the nonresponding TMD and IBS groups did worse in the neuropsychologic assessment than the responding TMD group, with higher memory deficits, levels of depression and fatigue, more sleep disturbances, and lower energy levels. Conclusions: These data suggested that 2 nonresponding chronic pain conditions of different origins may share similar neuropsychologic test results compared to a responding condition. These findings are consistent with the hypothesis that nonresponding chronic pain disorders, irrespective of peripheral location, may be regulated centrally and have similar neuropsychologic impacts.