Pain Experience in Pancreatitis: Strong Association of Genetic Risk Loci for Anxiety and PTSD in Patients With Severe, Constant, and Constant-Severe Pain.
Journal
The American journal of gastroenterology
ISSN: 1572-0241
Titre abrégé: Am J Gastroenterol
Pays: United States
ID NLM: 0421030
Informations de publication
Date de publication:
01 10 2021
01 10 2021
Historique:
received:
11
02
2021
accepted:
01
06
2021
pubmed:
9
7
2021
medline:
28
10
2021
entrez:
8
7
2021
Statut:
ppublish
Résumé
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. 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. 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). 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.
Identifiants
pubmed: 34236339
doi: 10.14309/ajg.0000000000001366
pii: 00000434-202110000-00028
pmc: PMC8531869
mid: NIHMS1712177
doi:
Banques de données
ClinicalTrials.gov
['NCT01545167']
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2128-2136Subventions
Organisme : NIDDK NIH HHS
ID : R56 DK061451
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000005
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024153
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIDDK NIH HHS
ID : R21 DK098560
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108327
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK061451
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK108306
Pays : United States
Organisme : NIDDK NIH HHS
ID : T32 DK063922
Pays : United States
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Type : ErratumIn
Type : CommentIn
Informations de copyright
Copyright © 2021 by The American College of Gastroenterology.
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