Loss of endogenous analgesia leads to delayed recovery from incisional pain in a rat model of chronic neuropathic pain
Loss of endogenous analgesia leads to delayed recovery from incisional pain in a rat model of chronic neuropathic pain
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慢性神经病理性疼痛大鼠模型中内源性镇痛的丧失导致切口痛恢复延迟
DOI：
10.1016/j.brainres.2019.146568
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发表时间：
2020
期刊：
影响因子：
2.9
通讯作者：
Saito
中科院分区：
文献类型：
--
作者：
Ohta J;Suto T;Kato D;Hiroki T;Obata H;Saito
背景术前疼痛和内源性镇痛功能受损是术后慢性持续性疼痛的危险因素。由脊神经结扎（SNL 6 W）诱导的慢性神经性疼痛模型显示内源性镇痛受损和切口疼痛恢复延迟。重复阿米替林治疗可以恢复内源性镇痛，但其延迟recovery的影响尚不清楚。MethodsA足底切口对侧的神经结扎在SNL 6 W大鼠。术后28 d采用von Frey细丝测试法测定大鼠的缩足阈值。阿米替林（10 mg·kg-1·d-1）或溶剂在围手术期给药13 d。要检查去甲肾上腺素能和胆碱能信号在脊髓背角，药理学拮抗作用的作用，每个神经递质浓度的测量，和免疫组织化学进行了covered.ResultsSNL6W动物的退缩阈值恢复到切口前的值需要28天手术后，而天真的动物在14天内恢复。鞘内注射α_2肾上腺素能受体拮抗剂（咪唑克生）或毒蕈碱胆碱能受体拮抗剂（阿托品）可降低未处理动物在POD 14和21的缩足阈，但对SNL 6 W大鼠无影响。反复阿米替林治疗可减轻SNL 6 W大鼠的延迟恢复，这种作用可被M胆碱能受体拮抗剂拮抗。此外，乙酰胆碱及其合成酶的浓度没有改变的treatment.ConclusionsNoradrenergic和胆碱能镇痛，这是必要的正常恢复，在SNL 6 W大鼠丢失。使用抗抑郁药增强内源性镇痛的策略，而不是简单的镇痛，可能有助于预防慢性疼痛患者的CPSP。
BackgroundPreoperative pain and impaired endogenous analgesia are risk factors of chronic postsurgical persistent pain (CPSP). A Chronic neuropathic pain model induced by spinal nerve ligation (SNL6W) shows impaired endogenous analgesia and delayed recovery from incisional pain. Repeated amitriptyline treatment can restore the endogenous analgesia, but its effects on delayed recovery are not clear.MethodsA plantar incision was made on the side contralateral to the nerve ligation in SNL6W rats. Withdrawal thresholds were measured by von Frey filament test until 28 d after surgery. Amitriptyline (10 mg·kg−1·d−1) or vehicle was administered for 13 d perioperatively. To examine the roles of noradrenergic and cholinergic signals in the spinal dorsal horn, pharmacological antagonism, measurement of each neurotransmitter concentration, and immunohistochemistry were conducted.ResultsRecovery of the withdrawal threshold of SNL6W animals to pre-incision values required 28 d after surgery, while naive animals recovered within 14 d. Intrathecal injection of alpha2 adrenoceptor antagonist (idazoxan) or muscarinic cholinergic receptor antagonist (atropine) decreased the withdrawal threshold on POD14 and 21 in naive animals, but not in SNL6W rats. Repeated amitriptyline treatment attenuated the delayed recovery in SNL6W rats, and the effect was antagonized by muscarinic cholinergic receptor antagonist. Beside the concentration of acetylcholine and its synthetic enzyme were not altered by the treatment.ConclusionsNoradrenergic and cholinergic analgesia, which is necessary for normal recovery, is lost in the SNL6W rats. A strategy to enhance endogenous analgesia using antidepressants, rather than simple analgesia, may help to prevent CPSP in chronic pain patients.
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影响因子：
2.5
作者：
EM Pogatzki;GF Gebhart;Tj. Brennan
通讯作者：
EM Pogatzki;GF Gebhart;Tj. Brennan
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影响因子：
2.9
作者：
W. A. Prado;Daniel K. Segalla
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影响因子：
7.4
作者：
Yarnitsky, David;Crispel, Yonathan;Granot, Michal
通讯作者：
Granot, Michal
影响因子：
7.4
作者：
Brennan TJ
通讯作者：
Brennan TJ
影响因子：
5.3
作者：
Koh, In Jun;Kim, Man Soo;In, Yong
通讯作者：
In, Yong