Svensson Camilla I, Schäfers Maria, Jones Toni L, Yaksh Tony L, Sorkin Linda S
Anesthesiology Research Labs, University of California San Diego, La Jolla, California 92093, USA.
J Pain. 2006 May;7(5):337-45. doi: 10.1016/j.jpain.2005.12.007.
This study examined effects of age (young rats, approximately 35 days, vs mature rats, approximately 75-110 days) on spinal nerve ligation (SNL)-induced tactile allodynia and phosphorylation of p38 (as measured by phospho-p38 MAP kinase [P-p38]) in dorsal root ganglia and spinal cord. Effects of SNL combined with spinal nerve transection also were assessed. Mature rats displayed milder SNL-induced allodynia than young rats. Addition of spinal nerve transection distal to the ligation in older animals resulted in an allodynia comparable to that seen in young animals. In DRG, both groups displayed early (5 h) and late (10 days) peaks in P-p38 following surgery as compared to naïve rats. Tight nerve ligation plus transection had no additional effect on P-p38 levels in DRG. In spinal cord, young rats had increased levels of P-p38 from 5 h to 3 days after SNL. Phosphorylated p38 levels then decreased, with a second peak at 10 days. In contrast, spinal cord from mature rats showed less early p38 phosphorylation, although they also displayed a late 10-day peak. Addition of a transection to the ligation produced restoration of the early peak along with intensification of allodynia. Alterations of spinal P-p38 at early time points thus seem to covary with intensity of tactile allodynia.
Age and modifications to spinal nerve ligation, a common model of neuropathic pain, influence spinal p38 phosphorylation and allodynia. Early levels of spinal P-p38 seem to covary with allodynia intensity. This may mean that small variations of an injury could affect the therapeutic window of a p38 antagonist.
本研究考察了年龄（幼鼠，约35天，与成年鼠，约75 - 110天）对脊髓神经结扎（SNL）诱导的触觉异常性疼痛以及背根神经节和脊髓中p38磷酸化（通过磷酸化p38丝裂原活化蛋白激酶[P-p38]测量）的影响。还评估了SNL联合脊髓神经横断的效果。成年鼠表现出比幼鼠更轻的SNL诱导的异常性疼痛。在老年动物中，在结扎远端添加脊髓神经横断导致异常性疼痛与幼龄动物中所见相当。在背根神经节中，与未处理的大鼠相比，两组在手术后均显示出P-p38的早期（5小时）和晚期（10天）峰值。紧密的神经结扎加横断对背根神经节中P-p38水平没有额外影响。在脊髓中，幼鼠在SNL后5小时至3天P-p38水平升高。然后磷酸化p38水平下降，在10天出现第二个峰值。相比之下，成年大鼠的脊髓早期p38磷酸化较少，尽管它们在10天也显示出晚期峰值。在结扎处添加横断导致早期峰值恢复以及异常性疼痛加剧。因此，早期时间点脊髓P-p38的改变似乎与触觉异常性疼痛的强度相关。
年龄以及对脊髓神经结扎（一种常见的神经性疼痛模型）的改变会影响脊髓p38磷酸化和异常性疼痛。脊髓P-p38的早期水平似乎与异常性疼痛强度相关。这可能意味着损伤的微小变化可能会影响p38拮抗剂的治疗窗口。
