* Postdoctoral Research Fellow, Department of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, Iowa, † Research Associate, Department of Internal Medicine, ‡ Associate Professor, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine and Veterans Medical Center, University of Iowa, Iowa City, Iowa, § Samir Gergis Professor and Vice Chair for Research, Departments of Anesthesia and Pharmacology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.
Anesthesiology. 2013 Nov;119(5):1186-97. doi: 10.1097/ALN.0b013e31829bd791.
Understanding the mechanisms underlying deep tissue pain in the postoperative period is critical to improve therapies. Using the in vitro plantar flexor digitorum brevis muscle-nerve preparation and patch clamp recordings from cultured dorsal root ganglia neurons innervating incised and unincised muscle, the authors investigated responses to various pH changes.
Incision including the plantar flexor digitorum brevis muscle or sham operation was made in the rat hind paw. On postoperative day 1, in vitro single-fiber recording was undertaken. On the basis of previous studies, the authors recorded from at least 40 fibers per group. Also DiI-labeled dorsal root ganglia innervating muscle from rats undergoing incision and a sham operation were cultured and tested for acid responses, using whole cell patch clamp recordings.
The prevalence of responsive group IV afferents to lactic acid pH 6.5 in the incision group (15 of 67; 22.3%) was greater than that in the control group (2 of 35; 5.7%; P=0.022). In dorsal root ganglia neurons innervating muscle, incision increased mean current amplitudes of acid-evoked currents; the acid-sensing ion channel blocker, amiloride 300 μM, inhibited more than 75% of the acid-evoked current, whereas, the transient receptor vanilloid receptor 1 blocker (AMG9810 1 μM) did not cause significant inhibition.
The authors' experiments demonstrated that incision increases the responses of flexor digitorum brevis muscle afferent fibers to weak acid solutions, and increased acid-evoked currents in dorsal root ganglia innervating muscle. The authors' data suggest that up-regulation of acid-sensing ion channels might underlie this increased chemosensitivity caused by surgery.
了解术后深部组织疼痛的发生机制对于改善治疗方法至关重要。作者使用体外比目鱼肌-神经制备和培养的背根神经节神经元的膜片钳记录,研究了对各种 pH 值变化的反应。
在大鼠后爪进行包括比目鱼肌在内的切口或假手术。术后第 1 天,进行体外单纤维记录。基于先前的研究,作者记录了每组至少 40 根纤维。此外,作者还培养了来自接受切口和假手术的大鼠的标记有 DiI 的背根神经节神经元,并使用全细胞膜片钳记录法测试其对酸的反应。
在切口组(15/67;22.3%)中,对乳酸 pH 值 6.5 有反应的 IV 型传入纤维的发生率高于对照组(2/35;5.7%;P=0.022)。在支配肌肉的背根神经节神经元中,切口增加了酸诱发电流的平均电流幅度;酸敏离子通道阻滞剂阿米洛利 300 μM 抑制了超过 75%的酸诱发电流,而瞬时受体香草素受体 1 阻滞剂(AMG9810 1 μM)则没有引起显著抑制。
作者的实验表明,切口增加了比目鱼肌传入纤维对弱酸溶液的反应性,并增加了支配肌肉的背根神经节中酸诱发电流。作者的数据表明,酸敏离子通道的上调可能是手术引起这种化学敏感性增加的基础。