衰老小鼠的痛觉变化及相关机制的研究

Changes of pain sensation in aging mice and related mechanism

目的探讨衰老对小鼠疼痛行为学以及脊髓背角胶质细胞活化的影响。方法使用von Frey实验分别检测3月龄、14月龄C57BL/6J雄性小鼠对机械刺激的缩足频率;建立足底切口痛、炎症痛以及单侧闭合性胫骨骨折痛3种疼痛模型,比较3月龄和14月龄小鼠在不同模型中对疼痛的敏感性以及疼痛维持时间。利用免疫荧光技术分别检测3月龄和14月龄小鼠正常状态或胫骨骨折术后28 d脊髓背角中GFAP、Iba-1和IL-1β的表达情况。结果正常生理条件下,14月龄老年小鼠的基础机械缩足频率低于3月龄的青年小鼠的基础机械缩足频率,痛觉不敏感。在切口痛模型中,相较于青年小鼠,14月龄老年小鼠的切口痛机械缩足频率在术后7 d高于青年组(P<0.05),未恢复至正常值;在炎性痛模型中,相较于青年小鼠,14月龄老年小鼠的缩足频率在造模后14 d高于青年组(P<0.05),不能恢复;在胫骨骨折术模型,相较于青年小鼠,14月龄老年小鼠的机械缩足阈值在术后28 d显著低于老年小鼠正常值或青年模型小鼠(P<0.05)。免疫荧光染色结果显示,在小鼠在骨折术后的第28 d,14月龄小鼠脊髓背角中的Iba-1、GFAP和IL-1β持续高表达并显著高于青年组(P<0.05)。结论衰老可能提高了小鼠的基础痛觉阈值,但却延长了病理性疼痛持续的时程,更易发展为创伤后慢性痛。这一现象的发生可能与老年小鼠脊髓背角中胶质细胞的持续活化有关。

Objective To detect the effects of aging on pain-related behavior and activation of glial cells in spinaldorsal horn in mice.Methods von Frey tests was used to assess mechanical sensitivity in mice.3-month-old and 14-month-old mice were employed to establish plantar incisional pain,inflammatory pain,and unilateral tibial fracture pain models.Immunofluorescence staining was used to detect the expression of GFAP,Iba-1 and IL-1βin spinal dorsal horn of mice be-fore or at 28;day after tibial fracture surgery.Results Under normal physiological conditions,the paw withdrawal frequen-cy in 14-month-old mice was lower than that in 3-month-old mice(P<0.05).Mechanical hyperalgesia induced by incis-ion surgery,CFA injection or tibial fracture surgery was significantly prolonged in 14-month-old mice as compared to 3-month-old mice(P<0.05).Immunostaining showed that the expression of GFAP,Iba-1 and IL-1βin spinal dorsal horn of 14-month-old mice was significantly higher than that of the old-na?ve or young-tibial fracture group on the 28th day after tibialfracture surgery(P<0.05).Conclusion Aging induced increased basal threshold of pain sensing as well as increased chronic pain sensitivity.The long-term a ctivation of glial cells and chronic inflammatory condition in spinal dorsal horn may par-ticipate in the prolonged tibial fracture-induced pain in the aged mice.