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胰腺炎疼痛质量在 1 年随访时发生变化,但 GP130 仍然是疼痛的生物标志物。

Pancreatitis pain quality changes at year 1 follow-up, but GP130 remains a biomarker for pain.

机构信息

Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, School of Medicine, University of Pittsburgh, PA, United States; Pittsburgh Center for Pain Research, School of Medicine, University of Pittsburgh, PA, United States; Department of Neurobiology, School of Medicine, University of Pittsburgh, PA, United States.

Department of Biostatistics, M.D. Anderson Cancer Center, Houston, TX, United States.

出版信息

Pancreatology. 2024 Nov;24(7):993-1002. doi: 10.1016/j.pan.2024.09.016. Epub 2024 Sep 18.

Abstract

BACKGROUND/OBJECTIVES: Debilitating abdominal pain is a common symptom affecting patients with chronic pancreatitis (CP). CP pain is dynamic due to multiple underlying mechanisms. The objective of this study was to 1) evaluate changes in pain phenotype at one year follow-up and 2) validate putative pain biomarkers in a prospective cohort study.

METHODS

The Neuropathic and Nociceptive PROMIS-PQ questionnaires were used to classify pain for participants with in the PROCEED study. Putative serum biomarkers were measured via immunoassay.

RESULTS

At enrollment, 17.6 % (120/681) subjects with CP reported no pain in the previous year. Of those, 29 % experienced pain during the 1 yr follow-up whereas 18 % of those with pain prior to enrollment reported no pain during the 1 yr follow-up period. Of the 393 subjects with PROMIS-PQ data at enrollment, 212 also had follow-up data at 1 yr. Approximately half (53.3 %) of those individuals changed pain phenotype between baseline and follow-up. At 1 yr, serum TGFβ1 level was negatively correlated with nociceptive T-scores (p = 0.006). GP130 was significantly correlated with both nociceptive (p = 0.012) and neuropathic T-scores (p = 0.043) at 1 yr, which is consistent with the previously published findings.

CONCLUSIONS

The positive association between TGFβ1 and pain is not maintained over time, suggesting it is a poor pain biomarker. However, serum GP130 is a consistent biomarker for mixed-type pain in CP. Preclinical studies show that targeting TGFβ1 or IL-6 (ligand for GP130) is sufficient to inhibit CP pain supporting further investigation of this as a potential therapeutic target.

摘要

背景/目的:腹部疼痛是影响慢性胰腺炎(CP)患者的常见症状。由于多种潜在机制,CP 疼痛是动态的。本研究的目的是 1)评估一年随访时疼痛表型的变化,2)在前瞻性队列研究中验证潜在的疼痛生物标志物。

方法

PROCEED 研究中使用神经病理性和伤害感受性 PROMIS-PQ 问卷对患者的疼痛进行分类。通过免疫测定法测量潜在的血清生物标志物。

结果

在入组时,17.6%(120/681)的 CP 患者在过去一年中没有疼痛。其中,29%的患者在 1 年随访期间出现疼痛,而在入组前有疼痛的患者中有 18%在 1 年随访期间无疼痛。在有 PROMIS-PQ 数据的 393 名患者中,212 名患者在 1 年时也有随访数据。大约一半(53.3%)的患者在基线和随访之间改变了疼痛表型。在 1 年时,血清 TGFβ1 水平与伤害感受 T 评分呈负相关(p=0.006)。GP130 与伤害感受(p=0.012)和神经病理性 T 评分(p=0.043)均显著相关,这与先前的研究结果一致。

结论

TGFβ1 与疼痛之间的正相关关系不会随着时间的推移而保持,这表明它是一种较差的疼痛生物标志物。然而,血清 GP130 是 CP 混合性疼痛的一致生物标志物。临床前研究表明,靶向 TGFβ1 或 IL-6(GP130 的配体)足以抑制 CP 疼痛,这支持进一步将其作为潜在治疗靶点的研究。

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