BACKGROUND: Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder (FGID) defined by chronic epigastric symptoms in the absence of organic abnormalities likely to explain them. Comorbidity with mood and anxiety disorders as well as with other FGIDs and functional somatic syndrome (FSS) is high. FD is characterized by abnormal regional cerebral activity in cognitive/affective pain modulatory circuits, but it is unknown which neurotransmitter systems are involved. The authors aimed to assess and compare in vivo cerebral cannabinoid-1 (CB1) receptor availability between FD patients and age-, gender- and BMI-matched healthy controls (HC). METHODS: Twelve FD patients and 12 matched HC were investigated using positron emission tomography (PET) with the CB1 receptor radioligand [(18)F]MK-9470. Nine of the patients received a second PET scan after a naturalistic follow-up period of 36 ± 9.6 months (range: 25.2-50.4 months). RESULTS: FD patients had significantly higher CB1 receptor availability in the cerebral regions involved in (visceral) nociception (brainstem, insula, anterior cingulate cortex) as well as in the homeostatic and hedonic regulation of food intake [hypothalamus, (ventral) striatum] (p < 0.05 corrected for multiple testing, region of interest analysis), which persisted after a follow-up period of 36 ± 9.6 months. CONCLUSIONS: Although these findings need replication in larger samples, they suggest that the abnormal brain activity in several of these regions, previously demonstrated in FD, may be due to a sustained endocannabinoid system dysfunction, identifying it as a potential novel target for treatment and warranting further studies to elucidate whether it is also a feature of other FGIDs or FSSs.
BACKGROUND:Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder (FGID) defined by chronic epigastric symptoms in the absence of organic abnormalities likely to explain them. Comorbidity with mood and anxiety disorders as well as with other FGIDs and functional somatic syndrome (FSS) is high. FD is characterized by abnormal regional cerebral activity in cognitive/affective pain modulatory circuits, but it is unknown which neurotransmitter systems are involved. The authors aimed to assess and compare in vivo cerebral cannabinoid-1 (CB1) receptor availability between FDpatients and age-, gender- and BMI-matched healthy controls (HC). METHODS: Twelve FDpatients and 12 matched HC were investigated using positron emission tomography (PET) with the CB1 receptor radioligand [(18)F]MK-9470. Nine of the patients received a second PET scan after a naturalistic follow-up period of 36 ± 9.6 months (range: 25.2-50.4 months). RESULTS:FDpatients had significantly higher CB1 receptor availability in the cerebral regions involved in (visceral) nociception (brainstem, insula, anterior cingulate cortex) as well as in the homeostatic and hedonic regulation of food intake [hypothalamus, (ventral) striatum] (p < 0.05 corrected for multiple testing, region of interest analysis), which persisted after a follow-up period of 36 ± 9.6 months. CONCLUSIONS: Although these findings need replication in larger samples, they suggest that the abnormal brain activity in several of these regions, previously demonstrated in FD, may be due to a sustained endocannabinoid system dysfunction, identifying it as a potential novel target for treatment and warranting further studies to elucidate whether it is also a feature of other FGIDs or FSSs.
Authors: Thomas R McCarty; Fouad Chouairi; Kelly E Hathorn; Walter W Chan; Christopher C Thompson Journal: J Clin Gastroenterol Date: 2022-04-01 Impact factor: 3.062
Authors: Stuart M Brierley; Beverley Greenwood-Van Meerveld; Giovanni Sarnelli; Keith A Sharkey; Martin Storr; Jan Tack Journal: Nat Rev Gastroenterol Hepatol Date: 2022-09-27 Impact factor: 73.082
Authors: Lucas Wauters; Ram Dickman; Vasile Drug; Agata Mulak; Jordi Serra; Paul Enck; Jan Tack; Anna Accarino; Giovanni Barbara; Serhat Bor; Benoit Coffin; Maura Corsetti; Heiko De Schepper; Dan Dumitrascu; Adam Farmer; Guillaume Gourcerol; Goran Hauser; Trygve Hausken; George Karamanolis; Daniel Keszthelyi; Carolin Malagelada; Tomislav Milosavljevic; Jean Muris; Colm O'Morain; Athanassos Papathanasopoulos; Daniel Pohl; Diana Rumyantseva; Giovanni Sarnelli; Edoardo Savarino; Jolien Schol; Arkady Sheptulin; Annemieke Smet; Andreas Stengel; Olga Storonova; Martin Storr; Hans Törnblom; Tim Vanuytsel; Monica Velosa; Marek Waluga; Natalia Zarate; Frank Zerbib Journal: United European Gastroenterol J Date: 2021-04 Impact factor: 4.623
Authors: Matthew E Sloan; Caroline W Grant; Joshua L Gowin; Vijay A Ramchandani; Bernard Le Foll Journal: Acta Pharmacol Sin Date: 2018-08-30 Impact factor: 6.150