Delta opioid receptor activation modulates affective pain and modality-specific pain hypersensitivity associated with chronic neuropathic pain.
Delta opioid receptor activation modulates affective pain and modality-specific pain hypersensitivity associated with chronic neuropathic pain.
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三角洲阿片受体激活调节与慢性神经性疼痛相关的情感疼痛和形式特异性疼痛超敏反应。
DOI：
10.1002/jnr.24680
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发表时间：
2022-01
影响因子：
4.2
通讯作者：
Olmstead MC
中科院分区：
文献类型：
--
作者：
Cahill CM;Holdridge SV;Liu SS;Xue L;Magnussen C;Ong E;Grenier P;Sutherland A;Olmstead MC
Delta阿片受体（DOR）激动剂可缓解各种慢性疼痛模型中的伤害性行为，包括神经性疼痛，而在无损伤的情况下对感觉阈值的影响很小。神经损伤诱导DOR功能增强的机制尚不清楚。我们使用神经性疼痛的周围神经损伤（PNI）模型来评估小鼠和大鼠DORs功能和定位的变化。鞘内给予DOR激动剂可逆转机械性异常痛和热痛觉过敏。在PNI大鼠中，DOR激动剂的剂量依赖性热抗感受作用向左偏移。给药DOR激动剂在PNI中产生条件位置偏好，但假手术小鼠没有，而DOR拮抗剂纳曲多在PNI中产生位置厌恶，但假手术小鼠没有，这表明内源性DOR活性参与抑制与损伤相关的疼痛。gtp - γ - s放射自显像显示PNI同侧脊髓背侧DOR功能增加。采用免疫金电镜和体内荧光激动剂测定脊髓背角DORs超微结构定位的变化。在假体中，DORs主要局限于细胞内区室。PNI显著增加了IV-V层树突谱内DORs的细胞表面表达。使用新生儿辣椒素治疗，我们发现DOR激动剂诱导的热抗感觉是通过在初级传入感觉神经元上表达的受体介导的，但不改变机械阈值。这些数据揭示了PNI对DORs的调控，并提示DORs的内源性激活在调节慢性疼痛状态中的重要性。
Delta opioid receptor (DOR) agonists alleviate nociceptive behaviors in various chronic pain models, including neuropathic pain, while having minimal effect on sensory thresholds in the absence of injury. The mechanisms underlying nerve injury-induced enhancement of DOR function are unclear. We used a peripheral nerve injury (PNI) model of neuropathic pain to assess changes in the function and localization of DORs in mice and rats. Intrathecal administration of DOR agonists reversed mechanical allodynia and thermal hyperalgesia. The dose-dependent thermal antinociceptive effects of DOR agonists were shifted to the left in PNI rats. Administration of DOR agonists produced a conditioned place preference in PNI, but not sham animals, whereas the DOR antagonist naltrindole produced a place aversion in PNI, but not sham mice, suggesting the engagement of endogenous DOR activity in suppressing pain associated with the injury. GTPγS autoradiography revealed an increase in DOR function in the dorsal spinal cord, ipsilateral to PNI. Immunogold electron microscopy and in vivo fluorescent agonist assays were used to assess changes in the ultrastructural localization of DORs in the spinal dorsal horn. In shams, DORs were primarily localized within intracellular compartments. PNI significantly increased the cell surface expression of DORs within lamina IV-V dendritic profiles. Using neonatal capsaicin treatment, we identified that DOR agonist-induced thermal antinociception was mediated via receptors expressed on primary afferent sensory neurons but did not alter mechanical thresholds. These data reveal that the regulation of DORs following PNI and suggest the importance of endogenous activation of DORs in regulating chronic pain states.
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影响因子：
10.6
作者：
Chu Sin Chung P;Keyworth HL;Martin-Garcia E;Charbogne P;Darcq E;Bailey A;Filliol D;Matifas A;Scherrer G;Ouagazzal AM;Gaveriaux-Ruff C;Befort K;Maldonado R;Kitchen I;Kieffer BL
通讯作者：
Kieffer BL
影响因子：
3.1
作者：
Henry MS;Gendron L;Tremblay ME;Drolet G
通讯作者：
Drolet G
影响因子：
5
作者：
BALSKUBIK, R;SHIPPENBERG, TS;HERZ, A
通讯作者：
HERZ, A
影响因子：
8.8
作者：
Brackley, Allison Doyle;Gomez, Ruben;Jeske, Nathaniel A.
通讯作者：
Jeske, Nathaniel A.
DOI：
10.1007/164_2017_42
发表时间：
2018-01-01
期刊：
DELTA OPIOID RECEPTOR PHARMACOLOGY AND THERAPEUTIC APPLICATIONS
影响因子：
--
作者：
Dripps, Isaac J.;Jutkiewicz, Emily M.
通讯作者：
Jutkiewicz, Emily M.