PKMζ is essential for spinal plasticity underlying the maintenance of persistent pain.
PKMζ is essential for spinal plasticity underlying the maintenance of persistent pain.
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DOI：
10.1186/1744-8069-7-99
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发表时间：
2011-12-20
期刊：
影响因子：
3.3
通讯作者：
Coderre TJ
中科院分区：
文献类型：
--
作者：
Laferrière A;Pitcher MH;Haldane A;Huang Y;Cornea V;Kumar N;Sacktor TC;Cervero F;Coderre TJ
当正常的保护性急性疼痛变得病理性持续时，就会发生慢性疼痛。我们在这里研究是否蛋白激酶C（PKC），PKM β，在不同的大脑区域的长期记忆存储的基础亚型，也维持脊髓背角（SCDH）介导的持续性疼痛的伤害性可塑性。皮肤损伤或脊髓刺激产生持续增加的PKM β，但不是其他非典型的PKCs在SCDH。抑制脊髓PKM β，但不是全长PKCs，逆转可塑性依赖性持续疼痛反应后爪福尔马林和继发性机械超敏反应和SCDH神经元致敏后爪辣椒素，不影响外周致敏依赖性原发性热过敏后爪辣椒素。抑制脊髓PKM β，但不是全长PKCs，也逆转了脊髓刺激与鞘内二羟苯甘氨酸诱导的大鼠后爪机械超敏反应。脊髓PKM β抑制也减轻了慢性缺血后疼痛（CPIP）大鼠缺血性损伤后3周的异常性疼痛，此时异常性疼痛取决于脊髓变化。相比之下，脊髓PKM β抑制并不影响坐骨神经慢性收缩性损伤（CCI）大鼠或缺血性损伤后早期CPIP大鼠的异常性疼痛，当异常性疼痛取决于持续的外周输入。这些结果表明，脊髓PKM神经元通过维持脊髓伤害性可塑性，对维持持续性疼痛是必不可少的。
Chronic pain occurs when normally protective acute pain becomes pathologically persistent. We examined here whether an isoform of protein kinase C (PKC), PKMζ, that underlies long-term memory storage in various brain regions, also sustains nociceptive plasticity in spinal cord dorsal horn (SCDH) mediating persistent pain. Cutaneous injury or spinal stimulation produced persistent increases of PKMζ, but not other atypical PKCs in SCDH. Inhibiting spinal PKMζ, but not full-length PKCs, reversed plasticity-dependent persistent painful responses to hind paw formalin and secondary mechanical hypersensitivity and SCDH neuron sensitization after hind paw capsaicin, without affecting peripheral sensitization-dependent primary heat hypersensitivity after hind paw capsaicin. Inhibiting spinal PKMζ, but not full-length PKCs, also reversed mechanical hypersensitivity in the rat hind paw induced by spinal stimulation with intrathecal dihydroxyphenylglycine. Spinal PKMζ inhibition also alleviated allodynia 3 weeks after ischemic injury in rats with chronic post-ischemia pain (CPIP), at a point when allodynia depends on spinal changes. In contrast, spinal PKMζ inhibition did not affect allodynia in rats with chronic contriction injury (CCI) of the sciatic nerve, or CPIP rats early after ischemic injury, when allodynia depends on ongoing peripheral inputs. These results suggest spinal PKMζ is essential for the maintenance of persistent pain by sustaining spinal nociceptive plasticity.
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