Hygge-Blakeman Karin, Brumovsky Pablo, Hao Jing-Xia, Xu Xiao-Jun, Hökfelt Tomas, Crawley Jacqueline N, Wiesenfeld-Hallin Zsuzsanna
Department of Laboratory Medicine, Division of Clinical Neurophysiology, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
Brain Res. 2004 Oct 29;1025(1-2):152-8. doi: 10.1016/j.brainres.2004.07.078.
The neuropeptide galanin may have a role in modulation of nociception, particularly after peripheral nerve injury. Here we assessed the development of neuropathic pain-like behaviors in mice overexpressing galanin under the dopamine beta-hydroxylase promoter. Unoperated galanin over-expressing mice exhibited a moderately reduced sensitivity to noxious heat. Both galanin over-expressing mice and wild-type controls developed mechanical and heat hypersensitivity after photochemically induced partial sciatic nerve ischemic injury. The magnitude and persistence of such pain-like behaviors were significantly less, and recovery was faster in galanin over-expressing mice compared to wild types. However, the recovery from toe-spread deficits did not differ between galanin over-expressing and wild-type mice after a crush injury to the sciatic nerve. Thus, early recovery in pain-like response is unlikely to result from accelerated regeneration in the galanin over-expressing mice. Immunohistochemical analysis showed that galanin is over-expressed both in small and large dorsal root ganglion cells in the transgene mouse, whereas large galanin-positive neurons were never seen in wild-type mice. The present results in general support an inhibitory role of galanin in nociception and indicate that increased availability of galanin in spinal dorsal horn at the time or shortly after nerve injury may reduce the development of pain-like behaviors in mice.
神经肽甘丙肽可能在伤害感受的调节中发挥作用，尤其是在周围神经损伤后。在此，我们评估了在多巴胺β-羟化酶启动子控制下过表达甘丙肽的小鼠中神经性疼痛样行为的发展情况。未手术的甘丙肽过表达小鼠对有害热的敏感性适度降低。在光化学诱导的部分坐骨神经缺血性损伤后，甘丙肽过表达小鼠和野生型对照均出现机械性和热超敏反应。与野生型相比，甘丙肽过表达小鼠此类疼痛样行为的程度和持续时间明显较轻，且恢复更快。然而，在坐骨神经挤压伤后，甘丙肽过表达小鼠和野生型小鼠在趾展缺陷恢复方面并无差异。因此，甘丙肽过表达小鼠疼痛样反应的早期恢复不太可能是由于再生加速所致。免疫组织化学分析表明，在转基因小鼠的小和大背根神经节细胞中甘丙肽均过表达，而在野生型小鼠中从未见过大的甘丙肽阳性神经元。目前的结果总体上支持甘丙肽在伤害感受中的抑制作用，并表明在神经损伤时或损伤后不久脊髓背角中甘丙肽可用性的增加可能会减少小鼠疼痛样行为的发展。
