Association of Serum Endocannabinoid Levels with Pancreatitis and Pancreatitis-Related Pain.

IF 3.1 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Marc T Goodman, Christina Lombardi, Alexa Torrens, Catherine Bresee, Jami L Saloman, Liang Li, Yunlong Yang, William E Fisher, Evan L Fogel, Christopher E Forsmark, Darwin L Conwell, Phil A Hart, Walter G Park, Mark Topazian, Santhi S Vege, Stephen K Van Den Eeden, Melena D Bellin, Dana K Andersen, Jose Serrano, Dhiraj Yadav, Stephen J Pandol, Daniele Piomelli
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Abstract

Background and Aims: This investigation examined the association of pancreatitis and pancreatitis-related pain with serum levels of two endocannabinoid molecules such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG) and two paracannabinoid molecules such as oleoylethanolamide (OEA) and palmitoylethanolamide (PEA). Methods: A case-control study was conducted within the Prospective Evaluation of Chronic Pancreatitis for Epidemiological and Translational Studies, including participants with no pancreas disease (N = 56), chronic abdominal pain of suspected pancreatic origin or indeterminate chronic pancreatitis (CP) (N = 22), acute pancreatitis (N = 33), recurrent acute pancreatitis (N = 57), and definite CP (N = 63). Results: Circulating AEA concentrations were higher in women than in men (p = 0.0499), and PEA concentrations were higher in obese participants than those who were underweight/normal or overweight (p = 0.003). Asymptomatic controls with no pancreatic disease had significantly (p = 0.03) lower concentrations of AEA compared with all disease groups combined. The highest concentrations of AEA were observed in participants with acute pancreatitis, followed by those with recurrent acute pancreatitis, chronic abdominal pain/indeterminant CP, and definite CP. Participants with pancreatitis reporting abdominal pain in the past year had significantly (p = 0.04) higher concentrations of AEA compared with asymptomatic controls. Levels of 2-AG were significantly lower (p = 0.02) among participants reporting abdominal pain in the past week, and pain intensity was inversely associated with concentrations of 2-AG and OEA. Conclusions: Endocannabinoid levels may be associated with stage of pancreatitis, perhaps through activation of the CB1 receptor. Validation of our findings would support the investigation of novel therapeutics, including cannabinoid receptor-1 antagonists, in this patient population.

血清内源性大麻素水平与胰腺炎及胰腺炎相关疼痛的关系
背景和目的:本研究探讨了胰腺炎和胰腺炎相关疼痛与血清中两种内源性大麻酰胺分子(如anandamide (AEA)和2-arachidonoylglycerol (2-AG))以及两种副大麻酰胺分子(如油酰乙醇酰胺(OEA)和棕榈酰乙醇酰胺(PEA))水平的关系。研究方法在 "慢性胰腺炎流行病学和转化研究前瞻性评估 "范围内开展病例对照研究,研究对象包括无胰腺疾病(56 人)、疑似胰腺源性慢性腹痛或不确定慢性胰腺炎(CP)(22 人)、急性胰腺炎(33 人)、复发性急性胰腺炎(57 人)和明确慢性胰腺炎(63 人)。研究结果女性血液中的 AEA 浓度高于男性(p = 0.0499),肥胖者血液中的 PEA 浓度高于体重不足/正常或超重者(p = 0.003)。没有胰腺疾病的无症状对照组的 AEA 浓度明显低于所有疾病组的总和(p = 0.03)。急性胰腺炎患者的 AEA 浓度最高,其次是复发性急性胰腺炎、慢性腹痛/不确定 CP 和明确 CP 患者。与无症状对照组相比,在过去一年中报告过腹痛的胰腺炎患者体内的 AEA 浓度明显更高(p = 0.04)。在报告过去一周有腹痛的参与者中,2-AG 的水平明显较低(p = 0.02),疼痛强度与 2-AG 和 OEA 的浓度成反比。结论内源性大麻素水平可能与胰腺炎的阶段有关,这可能是通过激活 CB1 受体实现的。验证我们的研究结果将有助于在这一患者群体中研究新型疗法,包括大麻素受体-1拮抗剂。
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来源期刊
Cannabis and Cannabinoid Research
Cannabis and Cannabinoid Research PHARMACOLOGY & PHARMACY-
CiteScore
6.80
自引率
7.90%
发文量
164
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