In our previous in vivo proton magnetic resonance spectroscopy (¹H MRS) study we found reduced levels of N-acetylaspartate in dorsolateral prefrontal cortex of chronic back pain patients. This study tests whether these chemical abnormalities can be detected in other pain states. Using ¹H MRS, we measured levels for N-acetylaspartate and other identifiable chemicals relative to creatine in four bilateral brain regions, including dorsolateral prefrontal cortex, orbitofrontal cortex, cingulate, and thalamus, in a case of intractable severe sympathetically mediated chronic pain [complex regional pain syndrome (CRPS) type I]. The subject's chemical variations in the brain were compared to the same regional chemicals in 10 normal subjects (age- and sex-matched). Univariate statistics showed reduced levels of N-acetylaspartate in bilateral dorsolateral prefrontal cortex and increased levels of myo-inositol in left orbitofrontal cortex of the patient with intractable severe CRPS type I. These data support our original hypothesis that depletion of N-acetylaspartate in dorsolateral prefrontal cortex is a chemical marker of chronic pain, indicating for neuronal degeneration. Unpredicted changes of orbitofrontal myo-inositol may be related to the specific mood/affective state in an extreme pain perception. This is the first report, which identifies chemical markers in the prefrontal cortex for objective measurement and monitoring of CRPS type I. This information might lead to valuable insights into diagnosis and future effective interventions of CRPS type I (e.g., prefrontal brain stimulation).