Neonatal pain experience and pain sensitivity trajectories in preterm infants: A longitudinal study of flexion withdrawal reflex thresholds over the first two years of age

IF 4 2区医学 Q1 CLINICAL NEUROLOGY

Journal of Pain Pub Date : 2025-09-11 DOI:10.1016/j.jpain.2025.105558

Weizi Wu , Wenxing Wang , Aolan Li , Jie Chen , Shabnam Lainwala , Adam P. Matson , Ming-Hui Chen , Jinlei Li , Xiaomei Cong

{"title":"Neonatal pain experience and pain sensitivity trajectories in preterm infants: A longitudinal study of flexion withdrawal reflex thresholds over the first two years of age","authors":"Weizi Wu , Wenxing Wang , Aolan Li , Jie Chen , Shabnam Lainwala , Adam P. Matson , Ming-Hui Chen , Jinlei Li , Xiaomei Cong","doi":"10.1016/j.jpain.2025.105558","DOIUrl":null,"url":null,"abstract":"<div><div>This study evaluated associations between early neonatal experiences during neonatal intensive care unit (NICU) hospitalization and the development of pain sensitivity, measured by flexion withdrawal reflex (FWR) thresholds, through 18–24 months corrected age in preterm infants. This longitudinal study (2017–2022) in Northeast U.S. specialized level III and IV NICUs monitored preterm infants for approximately 4–6 weeks for NICU pain/stress exposure (using the NICU Infant Stressor Scale - NISS) and analgesic use, assessing FWR thresholds post-discharge at 1, 4, 8–12, and 18–24 months of corrected age. 122 very preterm infants (63.1% male, 82.0% non-Black, 70.5% non-Hispanic) were enrolled, with a mean gestational age of 28.2 ± 2.4 weeks. The mean daily weighted NISS was 90.9 ± 19.9 (acute: 70.7; chronic: 20.2). FWR thresholds declined over time (1.11–0.7 g), suggesting increased population-level sensitivity. However, higher individual cumulative pain/stress exposure at NICU was associated with higher FWR thresholds (lower sensitivity) over time (β = 0.039, p = 0.042). The longitudinal effect of the pain/stress exposures (NISS score) on pain sensitivity (FWR) increased markedly over time in Black females, but was not observed in the Black male, Non-Black female, and Non-Black male subgroups (p < 0.05). Neonatal pain/stress exposure appears to reprogram long-term pain sensitivity development. These findings underscore the critical need for optimized pain management and tailored neuroprotective strategies for all high-risk infants.</div></div><div><h3>Perspective</h3><div>The FWR thresholds reflect the maturation of the nociceptive system in preterm infants from birth through 18–24 months of age. Neonatal cumulative pain/stress exposure is associated with altered maturation of FWR thresholds.</div></div>","PeriodicalId":51095,"journal":{"name":"Journal of Pain","volume":"37 ","pages":"Article 105558"},"PeriodicalIF":4.0000,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Pain","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1526590025007850","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

This study evaluated associations between early neonatal experiences during neonatal intensive care unit (NICU) hospitalization and the development of pain sensitivity, measured by flexion withdrawal reflex (FWR) thresholds, through 18–24 months corrected age in preterm infants. This longitudinal study (2017–2022) in Northeast U.S. specialized level III and IV NICUs monitored preterm infants for approximately 4–6 weeks for NICU pain/stress exposure (using the NICU Infant Stressor Scale - NISS) and analgesic use, assessing FWR thresholds post-discharge at 1, 4, 8–12, and 18–24 months of corrected age. 122 very preterm infants (63.1% male, 82.0% non-Black, 70.5% non-Hispanic) were enrolled, with a mean gestational age of 28.2 ± 2.4 weeks. The mean daily weighted NISS was 90.9 ± 19.9 (acute: 70.7; chronic: 20.2). FWR thresholds declined over time (1.11–0.7 g), suggesting increased population-level sensitivity. However, higher individual cumulative pain/stress exposure at NICU was associated with higher FWR thresholds (lower sensitivity) over time (β = 0.039, p = 0.042). The longitudinal effect of the pain/stress exposures (NISS score) on pain sensitivity (FWR) increased markedly over time in Black females, but was not observed in the Black male, Non-Black female, and Non-Black male subgroups (p < 0.05). Neonatal pain/stress exposure appears to reprogram long-term pain sensitivity development. These findings underscore the critical need for optimized pain management and tailored neuroprotective strategies for all high-risk infants.

Perspective

The FWR thresholds reflect the maturation of the nociceptive system in preterm infants from birth through 18–24 months of age. Neonatal cumulative pain/stress exposure is associated with altered maturation of FWR thresholds.

查看原文本刊更多论文

早产儿的新生儿疼痛体验和疼痛敏感性轨迹：前两年屈曲退缩反射阈值的纵向研究。

本研究评估了新生儿重症监护病房（NICU）住院期间的早期新生儿经历与疼痛敏感性发展之间的关系，通过挠曲退缩反射（FWR）阈值测量，直到早产儿18-24个月的矫正年龄。这项纵向研究（2017-2022）在美国东北部专门的III级和IV级NICU中对早产儿进行了大约4-6周的NICU疼痛/压力暴露（使用NICU婴儿压力源量表- NISS）和镇痛药的使用，评估出院后1、4、8-12和18-24个月的FWR阈值。122例极早产儿（63.1%为男性，82.0%为非黑人，70.5%为非西班牙裔）入组，平均胎龄28.2±2.4周。平均每日加权NISS为90.9±19.9（急性：70.7；慢性：20.2）。随着时间的推移，FWR阈值下降（1.11g至0.7 g），表明人群水平的敏感性增加。然而，随着时间的推移，NICU中较高的个体累积疼痛/应激暴露与较高的FWR阈值（较低的敏感性）相关（β = 0.039, p = 0.042）。疼痛/应激暴露（NISS评分）对疼痛敏感性（FWR）的纵向影响在黑人女性中随着时间的推移而显著增加，但在黑人男性、非黑人女性和非黑人男性亚组中没有观察到（p < 0.05）。新生儿疼痛/应激暴露似乎重新编程长期疼痛敏感性的发展。这些发现强调了为所有高危婴儿优化疼痛管理和定制神经保护策略的迫切需要。观点：FWR阈值反映了早产儿从出生到18 - 24个月的伤害感觉系统的成熟。新生儿累积疼痛/应激暴露与FWR阈值成熟改变有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Pain 医学-临床神经学

CiteScore

6.30

自引率

7.50%

发文量

441

审稿时长

42 days

期刊介绍： The Journal of Pain publishes original articles related to all aspects of pain, including clinical and basic research, patient care, education, and health policy. Articles selected for publication in the Journal are most commonly reports of original clinical research or reports of original basic research. In addition, invited critical reviews, including meta analyses of drugs for pain management, invited commentaries on reviews, and exceptional case studies are published in the Journal. The mission of the Journal is to improve the care of patients in pain by providing a forum for clinical researchers, basic scientists, clinicians, and other health professionals to publish original research.