Cingulate glutamate levels associate with pain in chronic pancreatitis patients

Abstract

Aims: Emerging evidence show that patients with chronic pancreatitis (CP) and abdominal pain have structural and functional alterations in the central nervous system. The aim was to investigate cerebral metabolic signatures in CP and the associations to various risk factors/clinical characteristics and patient outcomes. Methods: Magnetic resonance spectroscopy was used to measure brain metabolites in the anterior cingulate cortex (ACC), insula, prefrontal cortex and the parietal region in patients with CP and healthy controls. Subgroup analyses based on disease characteristics (alcoholic etiology of CP, diabetes and opioid treatment) were performed. Finally, relations to abdominal pain symptoms and quality of life scores were explored. Results: Thirty-one patients with CP (mean age 58.5 ± 9.2 years) and 23 healthy controls (54.6 ± 7.8 years) were included. Compared to healthy controls, patients had increased glutamate/creatine (glu/cre) levels in the ACC (1.24 ± 0.17 vs. 1.13 ± 0.21, p = .045) and reduced parietal N-acetylaspartate/creatine (NAA/cre) levels (1.44 ± 0.18 vs. 1.54 ± 0.12, p = .027). Patients with alcoholic etiology of CP had significant lower levels of parietal NAA/cre as compared to patients without alcoholic etiology and healthy controls (p < .006). Patients with a high level of ACC glu/cre reported more severe abdominal pain than their counterparts with a low level of ACC glu/cre (pain score 4.1 ± 2.7 vs.1.9 ± 2.3, p = .039). Conclusions: Cerebral spectroscopy revealed novel and complementary information on central pain mechanisms and alcohol mediated toxic effects in patients with CP. Our data suggest that cingulate glutamate levels associate with the patients clinical pain symptoms, while parietal NAA levels more likely associate with an alcoholic etiology of CP. Keywords: Chronic pancreatitis, Magnetic resonance imaging, Spectroscopy, Glutamate, Pain, Metabolites