Multidisciplinary Pain Center, Aichi Medical University, Nagakute, Aichi, 480-1195, Japan.
Eur J Pain. 2012 Mar;16(3):338-48. doi: 10.1002/j.1532-2149.2011.00026.x. Epub 2011 Dec 19.
It has been postulated that physical immobilization is an essential factor in developing chronic pain after trauma or surgery in an extremity. However, the mechanisms of sustained immobilization-induced chronic pain remain poorly understood. The present study, therefore, aimed to develop a rat model for chronic post-cast pain (CPCP) and to clarify the mechanism(s) underlying CPCP. To investigate the effects of cast immobilization on pain behaviours in rats, one hindlimb was immobilized for 2 weeks with a cast and remobilization was conducted for 10 weeks. Cast immobilization induced muscle atrophy and inflammatory changes in the immobilized hindlimb that began 2 h after cast removal and continued for 1 week. Spontaneous pain-related behaviours (licking and reduction in weight bearing) in the immobilized hindlimb were observed for 2 weeks, and widespread mechanical hyperalgesia in bilateral calves, hindpaws and tail all continued for 5-10 weeks after cast removal. A sciatic nerve block with lidocaine 24 h after cast removal transitorily abolished bilateral mechanical hyperalgesia in CPCP rats, suggesting that sensory inputs originating in the immobilized hindlimb contribute to the mechanism of both ipsilateral and contralateral hyperalgesia. Intraperitoneal injection of the free radical scavengers 4-hydroxy-2,2,6,6-tetramethylpiperydine-1-oxy1 or N-acetylcysteine 24 h after cast removal clearly inhibited mechanical hyperalgesia in bilateral calves and hindpaws in CPCP rats. These results suggest that cast immobilization induces ischaemia/reperfusion injury in the hindlimb and consequent production of oxygen free radicals, which may be involved in the mechanism of widespread hyperalgesia in CPCP rats.
有人假设，肢体创伤或手术后的慢性疼痛是身体固定不动的一个重要因素。然而，持续固定引起的慢性疼痛的机制仍知之甚少。因此，本研究旨在建立一种慢性石膏后疼痛（CPCP）大鼠模型，并阐明 CPCP 的发病机制。为了研究石膏固定对大鼠疼痛行为的影响，将一只后肢用石膏固定 2 周，并进行 10 周的再活动。石膏固定导致固定后肢的肌肉萎缩和炎症变化，这种变化在去除石膏后 2 小时开始，并持续 1 周。观察到固定后肢的自发性疼痛相关行为（舔舐和负重减少）持续 2 周，双侧小腿、后脚和尾巴的广泛机械性痛觉过敏持续 5-10 周。去除石膏后 24 小时用利多卡因进行坐骨神经阻滞可暂时消除 CPCP 大鼠的双侧机械性痛觉过敏，表明来源于固定后肢的感觉输入有助于同侧和对侧痛觉过敏的机制。去除石膏后 24 小时腹腔内注射自由基清除剂 4-羟基-2,2,6,6-四甲基哌啶-1-氧基 1 或 N-乙酰半胱氨酸可明显抑制 CPCP 大鼠双侧小腿和后脚的机械性痛觉过敏。这些结果表明，石膏固定可导致后肢的缺血/再灌注损伤和随后产生的氧自由基，这可能与 CPCP 大鼠的广泛痛觉过敏机制有关。
