Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model.
Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model.
复制标题
DOI：
10.3389/fnsyn.2021.748929
复制
发表时间：
2021
影响因子：
3.7
通讯作者：
Bae C
中科院分区：
文献类型：
--
作者：
Kearns A;Jayasi J;Liu X;Wang J;Shi Y;Chung JM;La JH;Tang SJ;Bae C
阿片类药物广泛用于缓解疼痛;然而，长期使用阿片类药物会导致疼痛敏感性增强的矛盾状态，称为“阿片类药物诱导的痛觉过敏（OIH）”。尽管OIH的临床重要性，其增强疼痛敏感性的详细机制仍不清楚。在这项研究中，我们测试是否重复吗啡诱导小鼠脊髓背角（SDH）的神经元回路极化。将GFP表达至神经激肽1受体表达神经元（sNK 1 Rn）和GABA能中间神经元（sGABAn）的转基因小鼠接受吗啡[20 mg/kg，每天一次，连续4天（i. p.）]出现了机械性过敏重复吗啡改变突触强度的SDH作为一个特定的细胞类型，但不是在性别依赖性的方式。在sNK 1 Rn和非紧张性放电神经元中，重复吗啡处理显著增加自发兴奋性突触后电流（sEPSC）和诱发EPSC（eEPSC）的频率。此外，重复吗啡治疗显着降低诱发抑制性突触后电流（eIPSC）在sNK 1 Rn。在sGABAn和紧张性放电神经元中，重复吗啡处理显著降低sEPSC频率和eEPSC，但sGABAn的eIPSC无变化。有趣的是，重复吗啡治疗显著降低sNK 1 Rn的神经元基强度，但对sGABAn没有影响。这些结果表明脊髓神经元回路极化可能是OIH的机制，并确定了一个潜在的治疗机制，以预防或治疗阿片类药物引起的疼痛。
Opioids are widely used for pain relief; however, chronic opioid use causes a paradoxical state of enhanced pain sensitivity, termed “Opioid-induced hyperalgesia (OIH).” Despite the clinical importance of OIH, the detailed mechanism by which it enhances pain sensitivity remains unclear. In this study, we tested whether repeated morphine induces a neuronal circuit polarization in the mouse spinal dorsal horn (SDH). Transgenic mice expressing GFP to neurokinin 1 receptor-expressing neurons (sNK1Rn) and GABAergic interneurons (sGABAn) that received morphine [20 mg/kg, once daily for four consecutive days (i.p.)] developed mechanical hypersensitivity. Repeated morphine altered synaptic strengths in the SDH as a specific cell-type but not in a gender-dependent manner. In sNK1Rn and non-tonic firing neurons, repeated morphine treatment significantly increased frequency of spontaneous excitatory postsynaptic current (sEPSC) and evoked EPSC (eEPSC). In addition, repeated morphine treatment significantly decreased evoked inhibitory postsynaptic current (eIPSC) in sNK1Rn. Conversely, in sGABAn and tonic firing neurons, repeated morphine treatment significantly decreased sEPSC frequency and eEPSC, but had no change of eIPSC in sGABAn. Interestingly, repeated morphine treatment significantly decreased neuronal rheobase of sNK1Rn but had no effect on sGABAn. These findings suggest that spinal neuronal circuit polarization maybe the mechanism of OIH and identify a potential therapeutic mechanism to prevent or treat opioid-induced pain.
登录
查看更多内容
影响因子：
7.4
作者：
Chen L;Malarick C;Seefeld L;Wang S;Houghton M;Mao J
通讯作者：
Mao J
影响因子：
7.4
作者：
Bittar A;Jun J;La JH;Wang J;Leem JW;Chung JM
通讯作者：
Chung JM
影响因子：
5.5
作者：
Grudt, TJ;Perl, ER
通讯作者：
Perl, ER
影响因子：
2.7
作者：
ESPEJO, EF;MIR, D
通讯作者：
MIR, D
影响因子：
7.6
作者：
Cabanero, David;Baker, Alyssa;Moron, Jose A.
通讯作者：
Moron, Jose A.