Distinct neurochemical features of acute and persistent pain
Distinct neurochemical features of acute and persistent pain
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DOI：
10.1073/pnas.96.14.7739
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发表时间：
1999-07-06
影响因子：
11.1
通讯作者：
Basbaum, AI
中科院分区：
文献类型：
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作者：
Basbaum, AI
为了解决急性和持续性疼痛的发展机制的神经化学，我们的实验室一直在研究与伤害性处理有关的基因产物缺失的小鼠。我们最近提出的小鼠与前速激肽原-A基因，编码肽物质P（SP）和神经激肽A（NKA）的缺失。这些研究已经确定了一种特定的行为表型，其中动物没有检测到“疼痛”强度的窗口;该窗口跨越热，机械和化学形式。然而，由组织或神经损伤产生的降低的热和机械退缩阈值仍然存在于突变小鼠中，因此，在损伤设置中伤害性处理中的阈值变化的行为表现似乎不需要SP或NKA。为了确定初级传入下游的相关神经化学因子，我们还研究了背角第二信使系统，该系统是组织和神经损伤诱导的持续性疼痛状态发展的基础。我们最近牵连的γ亚型蛋白激酶C（PKC γ）在神经损伤引起的神经病理性疼痛的发展。相比之下，PKC γ基因缺失小鼠的急性疼痛处理是完整的。总之，这些研究强调，急性和持续性疼痛有一个不同的神经化学。持续性疼痛应该被认为是神经系统的一种疾病状态，而不仅仅是一些其他疾病的长期急性疼痛症状。
To address the neurochemistry of the mechanisms that underlie the development of acute and persistent pain, our laboratory has been studying mice with deletions of gene products that have been implicated in nociceptive processing. We have recently raised mice with a deletion of the preprotachykinin-A gene, which encodes the peptides substance P (SP) and neurokinin A (NKA). These studies have identified a specific behavioral phenotype in which the animals do not detect a window of "pain" intensities; this window cuts across thermal, mechanical, and chemical modalities. The lowered thermal and mechanical withdrawal thresholds that are produced by tissue or nerve injury, however, were still present in the mutant mice, Thus, the behavioral manifestations of threshold changes in nociceptive processing in the setting of injury do not appear to require SP or NKA. To identify relevant neurochemical factors downstream of the primary afferent, we are also studying the dorsal horn second messenger systems that underlie the development of tissue and nerve injury-induced persistent pain states. We have recently implicated the gamma isoform of protein kinase C (PKC gamma) in the development of nerve injury-induced neuropathic pain. Acute pain processing, by contrast, is intact in the PKC gamma-null mice. Taken together, these studies emphasize that there is a distinct neurochemistry of acute and persistent pain. Persistent pain should be considered a disease state of the nervous system, not merely a prolonged acute pain symptom of some other disease conditions.