在健康人体中重复注射低剂量神经生长因子（NGF）可维持肌肉疼痛并促进缺血性收缩诱发的疼痛。

Repeated Injections of Low-Dose Nerve Growth Factor (NGF) in Healthy Humans Maintain Muscle Pain and Facilitate Ischemic Contraction-Evoked Pain.

机构信息

Department of Health Science and technology, Center for Neuroplasticity and Pain (CNAP), Aalborg University, Aalborg, Denmark.

Biomedicine, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.

出版信息

Pain Med. 2020 Dec 25;21(12):3488-3498. doi: 10.1093/pm/pnaa315.

DOI:10.1093/pm/pnaa315

PMID:33111942

Abstract

OBJECTIVE

Nerve growth factor (NGF) is essential for generating and potentiating pain responses. This double-blinded crossover study assessed NGF-evoked pain in healthy humans after repeated NGF injections in the tibialis anterior (TA) muscle compared with control injections of isotonic saline.

SUBJECTS

Twenty healthy subjects participated in two experimental phases; each consisted of seven sessions over 21 days.

METHODS

At day 0, day 2, and day 4, a low-dose NGF (1 µg) was injected. Data on daily self-reported muscle pain (using a Likert scale) were collected. Data on pressure pain thresholds (PPTs), pain evoked by nonischemic and ischemic muscle contractions (using a numerical rating scale [NRS]), pressure pain detection (PDT), and pain tolerance thresholds (PTTs) to cuff algometry were recorded before day 0 and at 1, 2, 4, 7, 10, and 21 days after the first injection. Temporal summation of pain (TSP) and conditioned pain modulation (CPM) were recorded to assess central pain mechanisms.

RESULTS

Likert scores remained elevated for 9 days after NGF injection (P<0.05). PPTs at the TA muscle were decreased at day 1 until day 7 after NGF injection compared with day 0 (P=0.05). In subjects presenting with NGF-induced muscle hyperalgesia, pain NRS scores evoked by nonischemic contractions were higher after NGF injection at day 4 and day 7 (P<0.04) compared with the control condition. At all time points, higher pain NRS scores were found with ischemic compared with nonischemic contractions (P<0.05). The pain NRS after ischemic contractions was elevated following prolonged NGF hyperalgesia at day 7 compared with the control condition and day 0 (P<0.04). The PDT, PTT, TSP, and CPM remained unchanged during the period of NGF-induced hyperalgesia.

CONCLUSIONS

Repeated low-dose NGF injections maintain muscle pain and potentiate pain evoked by ischemic contractions during prolonged NGF hyperalgesia.

摘要

目的

神经生长因子（NGF）对于产生和增强疼痛反应至关重要。本双盲交叉研究评估了健康人在前胫骨肌（TA）中反复注射 NGF 后与等渗盐水对照注射相比，NGF 诱发的疼痛。

受试者

20 名健康受试者参加了两个实验阶段；每个阶段由 21 天内的七次会议组成。

方法

在第 0 天、第 2 天和第 4 天，注射低剂量 NGF（1μg）。收集每日自我报告的肌肉疼痛（使用李克特量表）数据。记录压力疼痛阈值（PPT）、非缺血性和缺血性肌肉收缩引起的疼痛（使用数字评分量表[NRS]）、压力疼痛检测（PDT）和袖带测压仪的疼痛耐受阈值（PTT），在第 0 天之前和第 1、2、4、7、10 和 21 天第一次注射后。记录疼痛的时间总和（TSP）和条件性疼痛调制（CPM），以评估中枢疼痛机制。

结果

NGF 注射后 9 天内，李克特评分仍升高（P<0.05）。与第 0 天相比，NGF 注射后第 1 天至第 7 天 TA 肌肉的 PPT 降低（P=0.05）。在出现 NGF 诱导的肌肉痛觉过敏的受试者中，与对照条件相比，NGF 注射后第 4 天和第 7 天非缺血性收缩引起的疼痛 NRS 评分更高（P<0.04）。在所有时间点，缺血性收缩引起的疼痛 NRS 评分均高于非缺血性收缩（P<0.05）。与对照条件和第 0 天相比，第 7 天延长的 NGF 痛觉过敏后，缺血性收缩引起的疼痛 NRS 评分升高（P<0.04）。PDT、PTT、TSP 和 CPM 在 NGF 诱导的痛觉过敏期间保持不变。