TY - JOUR
T1 - Pain Experience in Pancreatitis
T2 - Strong Association of Genetic Risk Loci for Anxiety and PTSD in Patients with Severe, Constant, and Constant-Severe Pain
AU - Dunbar, Ellyn K.
AU - Greer, Phil J.
AU - Amann, Stephen T.
AU - Alkaade, Samer
AU - Banks, Peter
AU - Brand, Randall
AU - Conwell, Darwin L.
AU - Forsmark, Christopher E.
AU - Gardner, Timothy B.
AU - Guda, Nalini M.
AU - Lewis, Michele D.
AU - Machicado, Jorge D.
AU - Muniraj, Thiruvengadam
AU - Papachristou, Georgios I.
AU - Romagnuolo, Joseph
AU - Sandhu, Bimaljit S.
AU - Sherman, Stuart
AU - Slivka, Adam
AU - Wilcox, C. Mel
AU - Yadav, Dhiraj
AU - Whitcomb, David C.
N1 - Publisher Copyright:
© 2021 Wolters Kluwer Health. All rights reserved.
PY - 2021/10/1
Y1 - 2021/10/1
N2 - INTRODUCTION:Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are progressive inflammatory syndromes with variable features. Pain is the primary feature that contributes to low physical and mental quality of life with a third of patients reporting severe pain. Pain experience is worsened by depression. Here, we tested the hypothesis that genetic risk of the psychiatric conditions of anxiety and post-traumatic stress disorder (PTSD) is associated with pain in CP and RAP + CP subjects.METHODS:The study cohort included phenotyped and genotyped RAP and CP patients from the North American Pancreatitis Study II of European Ancestry. Candidate genetic association studies were based on the absence of pain vs pain that is constant, constant-severe, or severe. Twenty-eight candidate genetic loci for anxiety and PTSD risk were identified in the literature and were the focus of this study.RESULTS:We identified 24 significant pain-associated single nucleotide polymorphisms within 13 loci across the 3 pain patterns in CP and RAP + CP (P < 0.002). Thirteen anxiety or PTSD genes were within these pain loci indicating nonrandom associations (P < 4.885 × 10-23). CTNND2 was associated with all pain categories and all pancreatitis etiologies. Implicated systems include neuronal signaling (HTR2A, DRD3, NPY, and BDNF), hypothalamic-pituitary-adrenal axis (NR3C1 and FKBP5), and cell-cell interaction (CTNND2 and THBS2).DISCUSSION:A component of constant and severe pain in patients with RAP and CP is associated with genetic predisposition to anxiety and PTSD. Identification of patients at risk eligible for trials of targeted treatment as a component of a multidisciplinary pain management strategy should be formally evaluated.
AB - INTRODUCTION:Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are progressive inflammatory syndromes with variable features. Pain is the primary feature that contributes to low physical and mental quality of life with a third of patients reporting severe pain. Pain experience is worsened by depression. Here, we tested the hypothesis that genetic risk of the psychiatric conditions of anxiety and post-traumatic stress disorder (PTSD) is associated with pain in CP and RAP + CP subjects.METHODS:The study cohort included phenotyped and genotyped RAP and CP patients from the North American Pancreatitis Study II of European Ancestry. Candidate genetic association studies were based on the absence of pain vs pain that is constant, constant-severe, or severe. Twenty-eight candidate genetic loci for anxiety and PTSD risk were identified in the literature and were the focus of this study.RESULTS:We identified 24 significant pain-associated single nucleotide polymorphisms within 13 loci across the 3 pain patterns in CP and RAP + CP (P < 0.002). Thirteen anxiety or PTSD genes were within these pain loci indicating nonrandom associations (P < 4.885 × 10-23). CTNND2 was associated with all pain categories and all pancreatitis etiologies. Implicated systems include neuronal signaling (HTR2A, DRD3, NPY, and BDNF), hypothalamic-pituitary-adrenal axis (NR3C1 and FKBP5), and cell-cell interaction (CTNND2 and THBS2).DISCUSSION:A component of constant and severe pain in patients with RAP and CP is associated with genetic predisposition to anxiety and PTSD. Identification of patients at risk eligible for trials of targeted treatment as a component of a multidisciplinary pain management strategy should be formally evaluated.
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U2 - 10.14309/ajg.0000000000001366
DO - 10.14309/ajg.0000000000001366
M3 - Article
C2 - 34236339
AN - SCOPUS:85118283479
SN - 0002-9270
VL - 116
SP - 2128
EP - 2136
JO - American Journal of Gastroenterology
JF - American Journal of Gastroenterology
IS - 10
ER -