Center for Neuroplasticity and Pain (CNAP), SMI, Faculty of Medicine, Aalborg University, Aalborg, Denmark.
Biomedicine, Department of Health Science and Technology, Faculty of Medicine, Aalborg University, Aalborg, Denmark.
Eur J Pain. 2019 Nov;23(10):1814-1825. doi: 10.1002/ejp.1455. Epub 2019 Aug 5.
Intramuscular injection of Nerve Growth Factor (NGF) may influence the responsiveness of active chemo-sensitive channels affecting muscle pain sensitivity. This double-blinded crossover study in healthy humans assessed contraction-evoked pain responses and pain sensitivity during acute ischaemia in the tibialis anterior (TA) muscle before and 24 hr after five distributed NGF injections (1 µg, 4 cm interval) compared with control injections (isotonic-saline).
Twenty-one subjects participated in two experimental phases, each including five sessions over 7 days, with a gap of 4 weeks in-between. Muscle pain intensity evoked with daily functional tasks (Likert scale score) was collected using a paper diary. Pain intensity evoked by ischaemic and non-ischaemic contractions numerical rating scale (NRS) was collected at Day0 and Day1. Pressure pain thresholds (PPTs) on the TA were recorded before (Day0), 3 hr, 1, 3, and 7 days post-injection, and after the ischaemic-contractions and post-cuff deflation at Day0 and Day1.
Increased Likert scores of pain were present for 7 days after NGF compared to control injections (p < .05). Higher NRS pain scores of ischaemic-contractions were seen when contracting the muscle injected with NGF compared to baseline (p = .003) and control (p = .012). Pain during non-ischaemic contractions was not significantly affected by NGF injections. Decreased PPTs were found at 3 hr, Day1 and Day3 post-injection (p < .05) in both conditions. Compared with pre-contractions, PPTs were increased following ischaemic contractions at Day0 (p < .05) and Day1 (p < .05) in both conditions.
This study showed that ischaemic contraction-evoked pain was facilitated in an NGF-sensitized muscle.
Acidification of the muscle environment may affect muscle nociceptors and pain by different mechanisms, including activation of ASIC and TRPV1. In this study, pain evoked following ischaemic contractions was increased in the Nerve Growth Factor (NGF)-sensitized muscle compared with non-ischaemic contractions and in the non-sensitized muscle. These findings illustrate that responses of peripheral afferents under ischaemic conditions are altered by a pre-sensitized muscle. This highlights the role of growth factors, including NGF, in peripheral muscle sensitization with clinical implications for ischaemic myalgia.
肌肉内注射神经生长因子（NGF）可能会影响活跃的化学敏感通道的反应性，从而影响肌肉疼痛敏感性。本项在健康人群中开展的双盲交叉研究，在胫骨前肌（TA）急性缺血前后 24 小时，评估了 5 次分布的 NGF 注射（1μg，4cm 间隔）与对照注射（等渗盐水）相比，收缩诱发的疼痛反应和疼痛敏感性。
21 名受试者参加了两个实验阶段，每个阶段包括 7 天内的 5 个疗程，两个阶段之间间隔 4 周。使用纸质日记收集每日功能任务引起的肌肉疼痛强度（Likert 量表评分）。在第 0 天和第 1 天，通过缺血性和非缺血性收缩诱发的数字评定量表（NRS）收集疼痛强度。在第 0 天、第 3 小时、第 1 天、第 3 天和第 7 天，在注射前（第 0 天）、缺血性收缩后和袖带放气后，记录 TA 的压痛阈值（PPT）。
与对照注射相比，NGF 注射后 7 天内疼痛的 Likert 评分增加（p<0.05）。与基线（p=0.003）和对照（p=0.012）相比，用 NGF 注射的肌肉收缩时，缺血性收缩引起的 NRS 疼痛评分更高。NGF 注射并未显著影响非缺血性收缩时的疼痛。两种情况下，在第 3 小时、第 1 天和第 3 天，注射后 PPT 降低（p<0.05）。与收缩前相比，在第 0 天（p<0.05）和第 1 天（p<0.05），缺血性收缩后 PPT 增加。
本研究表明，在 NGF 敏化的肌肉中，缺血性收缩诱发的疼痛得到促进。
肌肉环境的酸化可能通过不同的机制影响肌肉伤害感受器和疼痛，包括激活 ASIC 和 TRPV1。在这项研究中，与非缺血性收缩和非敏化肌肉相比，在 NGF 敏化的肌肉中，缺血性收缩后引起的疼痛增加。这些发现表明，在缺血条件下，外周传入纤维的反应通过预先敏化的肌肉发生改变。这强调了生长因子（包括 NGF）在外周肌肉敏化中的作用，对缺血性肌痛具有临床意义。
