Preemptive Analgesic Effect of Intrathecal Applications of Neuroactive Steroids in a Rodent Model of Post-Surgical Pain: Evidence for the Role of T-Type Calcium Channels.
Preemptive Analgesic Effect of Intrathecal Applications of Neuroactive Steroids in a Rodent Model of Post-Surgical Pain: Evidence for the Role of T-Type Calcium Channels.
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DOI：
10.3390/cells9122674
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发表时间：
2020-12-12
期刊：
影响因子：
6
通讯作者：
Jevtovic-Todorovic V
中科院分区：
文献类型：
--
作者：
Tat QL;Joksimovic SM;Krishnan K;Covey DF;Todorovic SM;Jevtovic-Todorovic V
切开后疼痛的先发制人管理仍然具有挑战性。在这里，我们研究了预先使用对低电压激活的T型钙通道(T通道)和γ-氨基丁酸A(GAAA)受体具有活性的神经活性类固醇在术后疼痛的发生和维持中的作用。我们使用对GABAA受体和/或T通道有不同作用的神经活性类固醇：Alphaxone(GABA能和T通道抑制剂)、ECN(T通道抑制剂)、CDNC24(GABA能药)，并将它们与已有的止痛药吗啡(一种阿片激动剂，对T通道和GABAA受体都没有已知作用)进行比较。成年雌性大鼠右爪足底皮肤和肌肉切开。在出现术后疼痛之前或之后，我们都在鞘内注射了所选择的药物。通过研究机械超敏反应来监测疼痛的发展。Alphaxone和ECN，但不是吗啡，在先发制人给药时，在减轻机械性痛觉过敏方面有效，而吗啡只有在疼痛发生后才能提供剂量依赖的疼痛缓解。另一方面，CDNC24没有提供任何止痛益处。与吗啡不同，抑制T-电流的神经活性类固醇-Alphaxone和ECN-是有效的超前止痛剂，可能为治疗切开后疼痛，特别是机械超敏反应提供一种有前途的治疗方法。
Preemptive management of post-incisional pain remains challenging. Here, we examined the role of preemptive use of neuroactive steroids with activity on low-voltage activated T-type Ca2+ channels (T-channels) and γ-aminobutyric acid A (GABAA) receptors in the development and maintenance of post-incisional pain. We use neuroactive steroids with distinct effects on GABAA receptors and/or T-channels: Alphaxalone (combined GABAergic agent and T-channel inhibitor), ECN (T-channel inhibitor), CDNC24 (GABAergic agent), and compared them with an established analgesic, morphine (an opioid agonist without known effect on either T-channels or GABAA receptors). Adult female rats sustained the skin and muscle incision on the plantar surface of the right paw. We injected the agents of choice intrathecally either before or after the development of post-incisional pain. The pain development was monitored by studying mechanical hypersensitivity. Alphaxalone and ECN, but not morphine, are effective in alleviating mechanical hyperalgesia when administered preemptively whereas morphine provides dose-dependent pain relief only when administered once the pain had developed. CDNC24 on the other hand did not offer any analgesic benefit. Neuroactive steroids that inhibit T-currents—Alphaxalone and ECN—unlike morphine, are effective preemptive analgesics that may offer a promising therapeutic approach to the treatment of post-incisional pain, especially mechanical hypersensitivity.
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影响因子：
5.7
作者：
Chang, Wen-Kuei;Tao, Yuan-Xiang;Chu, Ya-Chun
通讯作者：
Chu, Ya-Chun
DOI：
10.1016/0960-0760(90)90490-c
发表时间：
1990-11-20
影响因子：
4.1
作者：
BAULIEU, EE;ROBEL, P
通讯作者：
ROBEL, P
影响因子：
11.4
作者：
Deval, Emmanuel;Noel, Jacques;Lingueglia, Eric
通讯作者：
Lingueglia, Eric
影响因子：
11.4
作者：
Bourinet, E;Alloui, A;Nargeot, J
通讯作者：
Nargeot, J
影响因子：
9.8
作者：
Atluri, N.;Joksimovic, S. M.;Jevtovic-Todorovic, V.
通讯作者：
Jevtovic-Todorovic, V.