Svensson Peter, Cairns Brian E, Wang Kelun, Arendt-Nielsen Lars
Department of Clinical Oral Physiology, Dental School, University of Aarhus, Vennelyst Boulevard 9, DK-8000 Aarhus C, Denmark.
Pain. 2003 Jul;104(1-2):241-7. doi: 10.1016/s0304-3959(03)00012-5.
Nerve growth factor (NGF) is a neurotrophic protein with a pivotal role in development and maintenance of the nervous system on one side and inflammatory and neuropathic pain states on the other. NGF causes clear signs of behavioral hyperalgesia in animal models and following intradermal and systemic administration in humans. The present double-blinded, placebo-controlled study was designed to test quantitatively the effect and duration (1h, 1, 7, 14, 21 and 28 days) of NGF (5 microg in 0.2 ml) injected into the masseter muscle. Pressure pain thresholds (PPT) and pressure tolerance thresholds (PTOL) were used as indices of mechanical allodynia and hyperalgesia in the jaw-closing muscles. In addition, perceived pain intensity was assessed by the subjects on a 0-10 numerical rating scale (NRS) with the jaw at rest and in relation to various oral functions (chewing, yawning, talking, swallowing, drinking and smiling). Repeated measures analysis of variance (ANOVA) was used to test for significant effects. Injection of NGF into the masseter muscle was associated with significantly reduced PPT for 7 days (ANOVA: P<0.001) and PTOL for 1 day (P<0.001). Buffered isotonic saline injections into the masseter muscle also significantly lowered the PPT after 1 day but to a significantly smaller extent than the NGF injections (P<0.001) and isotonic saline had no significant effects on PTOL. In contrast, assessment of PPT and PTOL in the non-injected temporalis muscles demonstrated a significant increase after 14-28 days (P<0.001), which may have reflected an adaptation to the test procedure. NRS scores of chewing and yawning were significantly increased for 7 days following NGF injection (P<0.001). Systemic adverse effects were noted in one subject who reported fever and slight discomfort about 8h after the NGF injection. In conclusion, this is the first study to show that injection of NGF into the human masseter muscle causes local signs of mechanical allodynia and hyperalgesia that persist for at least 7 days as well as pain during strenuous jaw movement. The present pain model is safe and may be used to gain further insight into the neurobiological mechanisms of muscle pain and sensitization.
神经生长因子（NGF）是一种神经营养蛋白，一方面在神经系统的发育和维持中起关键作用，另一方面在炎症性疼痛和神经性疼痛状态中也起关键作用。在动物模型以及在人类进行皮内注射和全身给药后，NGF会引发明显的行为性痛觉过敏迹象。本双盲、安慰剂对照研究旨在定量测试注射到咬肌中的NGF（0.2 ml中含5微克）的效果和持续时间（1小时、1天、7天、14天、21天和28天）。压力痛阈（PPT）和压力耐受阈（PTOL）被用作闭口肌中机械性异常性疼痛和痛觉过敏的指标。此外，受试者在静息状态下以及与各种口腔功能（咀嚼、打哈欠、说话、吞咽、饮水和微笑）相关时，通过0至10的数字评分量表（NRS）评估疼痛强度感受。采用重复测量方差分析（ANOVA）来检验显著效应。向咬肌注射NGF会使PPT在7天内显著降低（ANOVA：P<0.001），PTOL在1天内显著降低（P<0.001）。向咬肌注射缓冲等渗盐水在1天后也会显著降低PPT，但程度明显小于NGF注射（P<0.001），且等渗盐水对PTOL无显著影响。相比之下，对未注射的颞肌进行PPT和PTOL评估显示，在14 - 28天后显著增加（P<0.001），这可能反映了对测试程序的适应。NGF注射后7天内，咀嚼和打哈欠的NRS评分显著增加（P<0.001）。一名受试者在注射NGF约8小时后报告发热和轻微不适，出现了全身性不良反应。总之，这是第一项表明向人类咬肌注射NGF会导致局部机械性异常性疼痛和痛觉过敏迹象且持续至少7天以及在剧烈下颌运动时疼痛的研究。目前的疼痛模型是安全的，可用于进一步深入了解肌肉疼痛和致敏的神经生物学机制。
