Smith Peter G, Liu Manxi
Department of Molecular and Integrative Physiology and The R.L. Smith Mental Retardation Research Center, University of Kansas Medical Center, Kansas City, KS 66160-7401, USA.
Cell Tissue Res. 2002 Mar;307(3):281-91. doi: 10.1007/s00441-001-0477-8. Epub 2002 Feb 5.
The role of sensory nociceptor nerves in cutaneous wound healing was investigated following full-thickness 4-mm diameter dorsal cutaneous excision wounding of rats on postnatal day 12. In rats with intact innervation, wounds at 3 days contained large numbers of TUNEL- and BRDU-labeled nuclei, consistent with inflammatory cell death and granulation cell proliferation. Wound area and volume decreased through 11 days in concert with a transient appearance of alpha-smooth muscle actin-immunoreactive myofibroblasts, declining rates of cell division, and increased occurrence of apoptotic cells. Sensory denervation by capsaicin injections on postnatal days 2 and 9 reduced calcitonin gene-related peptide-immunoreactive wound innervation persistently by up to 43%. This was associated with increased wound surface area and volume, and delays in scab loss and re-epithelialization. Relative to control wounds, granulation tissue showed increased myofibroblast content at 5-7 days. Capsaicin-treated rats had more BRDU-labeled cells, including myofibroblasts, through day 7. Numbers of TUNEL apoptotic cells per unit area of tissue section were reduced by denervation in both early and late stages of healing. We conclude that partial loss of sensory innervation impairs cutaneous wound healing in developing rats, as manifested by delayed re-epithelialization and failure of the wound area to decrease normally through at least 21 days. This is associated with an abnormally enlarged wound tissue volume resulting from increased granulation cell proliferation without proportionate increases in apoptosis. These findings suggest that nociceptor innervation plays a critical role in wound healing by regulating wound cellularity.
在出生后第12天对大鼠进行直径4毫米的背部全层皮肤切除创伤后，研究了感觉伤害性感受器神经在皮肤伤口愈合中的作用。在神经支配完整的大鼠中，3天时伤口含有大量TUNEL和BRDU标记的细胞核，这与炎性细胞死亡和肉芽细胞增殖一致。伤口面积和体积在11天内逐渐减小，同时伴有α-平滑肌肌动蛋白免疫反应性肌成纤维细胞的短暂出现、细胞分裂率下降以及凋亡细胞发生率增加。在出生后第2天和第9天注射辣椒素进行感觉去神经支配，可使降钙素基因相关肽免疫反应性伤口神经支配持续减少高达43%。这与伤口表面积和体积增加、痂皮脱落延迟和再上皮化延迟有关。相对于对照伤口，肉芽组织在5 - 7天时肌成纤维细胞含量增加。辣椒素处理的大鼠在第7天时含有更多的BRDU标记细胞，包括肌成纤维细胞。在愈合的早期和晚期，去神经支配均使单位面积组织切片中的TUNEL凋亡细胞数量减少。我们得出结论，感觉神经支配的部分丧失会损害发育中大鼠的皮肤伤口愈合，表现为再上皮化延迟以及伤口面积至少在21天内未能正常减小。这与肉芽细胞增殖增加导致伤口组织体积异常增大且凋亡没有相应增加有关。这些发现表明，伤害性感受器神经支配通过调节伤口细胞数量在伤口愈合中起关键作用。
