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慢性疼痛与抑郁是长期困扰人类的两大疾病，严重影响着人们的生活质量和身心健康。慢性疼痛与实际或潜在的组织损伤有关，易导致不同程度的焦虑、抑郁等情感障碍。抑郁症是以显著而持久的情感低落、思维迟钝，以及言语动作减少、迟缓为典型症状的疾病，对疼痛的敏感性较高。大量的临床研究发现慢性疼痛和抑郁有极高的共病率，疼痛程度与抑郁的严重强度存在正相关，而抑郁症状可延长疼痛时间、加深疼痛程度，从而形成疼痛和抑郁的恶性循环。这提示慢性疼痛与抑郁之间可能存在共同的发病机制。磷酸二酯酶（phosphodiesterase， PDEs）具有水解细胞内第二信使环磷酸腺苷和环磷酸鸟苷的作用。近几年， PDEs已逐渐成为疼痛及焦虑抑郁的研究热点。因此，本文对慢性疼痛与抑郁之间的关联性及PDEs在二者共病中的可能作用做一简要综述。
","endNoteUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=EndNote&id=465","reference":"| 1 | Huang X， Xiaokaiti Y， Yang J， et al. Inhibition of phosphodiesterase 2 reverses gp91phox oxidase-mediated depression- and anxiety-like behavior［J］. Neuropharmacology， 2018， 143： 176. |
| 2 | Wang H， Zhang FF， Xu Y， et al. The phosphodiesterase-4 inhibitor roflumilast， a potential treatment for the comorbidity of memory loss and depression in alzheimer's disease： a preclinical study in APP/PS1 transgenic mice［J］. Int J Neuropsychopharmacol， 2020， 23（10）： 700. |
| 3 | Kruse LS， Sandholdt NT， Gammeltoft S， et al. Phosphodiesterase 3 and 5 and cyclic nucleotide-gated ion channel expression in rat trigeminovascular system［J］. Neurosci Lett， 2006， 404（1/2）： 202. |
| 4 | Jankowska A， Sata?a G， Ko?aczkowski M， et al. Novel anilide and benzylamide derivatives of arylpiperazinylalkanoic acids as 5-HT1A/5-HT7 receptor antagonists and phosphodiesterase 4/7 inhibitors with procognitive and antidepressant activity［J］. Eur J Med Chem， 2020， 201： 112437. |
| 5 | 宋学军， 樊碧发， 万有， 等. 国际疼痛学会新版疼痛定义修订简析［J］. 中国疼痛医学杂志， 2020， 26（9）： 641. |
| 6 | Ohayon MM， Schatzberg AF. Chronic pain and major depressive disorder in the general population［J］. J Psychiatr Res， 2010， 44（7）： 454. |
| 7 | 徐子尧， 黄亚玲， 朱光强， 等. 中国青少年抑郁症患者非自杀性自伤行为发生率的Meta分析［J］. 四川精神卫生， 2022， 35（4）： 331. |
| 8 | Arango-Dávila CA， Rincón-Hoyos HG. Depressive disorder， anxiety disorder and chronic pain： multiple manifestations of a common clinical and pathophysiological core［J］. Rev Colomb Psiquiatr （Engl Ed）， 2018， 47（1）： 46. |
| 9 | 史妙， 王锦琰， 罗非. 疼痛和抑郁［J］. 中国药物与临床， 2009， 9（9）： 789. |
| 10 | Liu YT， Shao YW， Yen CT， et al. Acid-induced hyperalgesia and anxio-depressive comorbidity in rats［J］. Physiol Behav， 2014， 131： 105. |
| 11 | Boadas-Vaello P， Homs J， Portero-Tresserra M， et al. Graded photochemical spinal cord injury results in chronic hyperalgesia and depression-like behaviour but no anxiety exacerbation in female BALB/c mice［J］. Neurosci Lett， 2018， 664： 98. |
| 12 | Bura AS， Guegan T， Zamanillo D， et al. Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain［J］. Eur J Pain， 2013， 17（6）： 832. |
| 13 | Li J， Li Y， Zhang B， et al. Why depression and pain often coexist and mutually reinforce： role of the lateral habenula［J］. Exp Neurol， 2016， 284（Pt A）： 106. |
| 14 | Burke NN， Finn DP， Roche M. Neuroinflammatory mechanisms linking pain and depression［J］. Mod Trends Pharmacopsychiatry， 2015， 30： 36. |
| 15 | Harth M， Nielson WR. Pain and affective distress in arthritis： relationship to immunity and inflammation［J］. Expert Rev Clin Immunol， 2019， 15（5）： 541. |
| 16 | Aroke EN， Joseph PV， Roy A， et al. Could epigenetics help explain racial disparities in chronic pain？［J］. J Pain Res， 2019， 12： 701. |
| 17 | Matthews SC， Strigo IA， Simmons AN， et al. Decreased functional coupling of the amygdala and supragenual cingulate is related to increased depression in unmedicated individuals with current major depressive disorder［J］. J Affect Disord， 2008， 111（1）： 13. |
| 18 | Delhaye S， Bardoni B. Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders［J］. Mol Psychiatry， 2021， 26（9）： 4570. |
| 19 | 严伟， 陈玲， 王飞， 等. 磷酸二酯酶2对抑郁焦虑及认知障碍等中枢神经疾病的调节作用［J］. 中国临床药理学与治疗学， 2013， 18（12）： 1424. |
| 20 | 徐江平， 汪海涛. 磷酸二酯酶4作为抗抑郁药物作用靶点的研究［J］. 遵义医学院学报， 2014， 37（5）： 449. |
| 21 | Plummer MS， Cornicelli J， Roark H， et al. Discovery of potent， selective， bioavailable phosphodiesterase 2 （PDE2） inhibitors active in an osteoarthritis pain model， part Ⅰ： transformation of selective pyrazolodiazepinone phosphodiesterase 4 （PDE4） inhibitors into selective PDE2 inhibitors［J］. Bioorg Med Chem Lett， 2013， 23（11）： 3438. |
| 22 | Wang JN， Zhao XJ， Liu ZH， et al. Selective phosphodiesterase-2A inhibitor alleviates radicular inflammation and mechanical allodynia in non-compressive lumbar disc herniation rats［J］. Eur Spine J， 2017， 26（7）： 1961. |
| 23 | 文睿婷， 张汉霆， 冯婉玉， 等. 磷酸二酯酶-4的中枢功能研究进展［J］. 中国药理学通报， 2014， 30（4）： 452. |
| 24 | Zhu X， Li W， Li Y， et al. The antidepressant- and anxiolytic-like effects of resveratrol： involvement of phosphodiesterase-4D inhibition［J］. Neuropharmacology， 2019， 153： 20. |
| 25 | 底妍， 和晓韵， 嵇睛， 等. 鞘内注射PDE4B-siRNA对L5脊神经结扎大鼠痛觉高敏的影响［J］. 临床麻醉学杂志， 2013， 29（6）： 604. |
| 26 | Zhang FF， Wang H， Zhou YM， et al. Inhibition of phosphodiesterase-4 in the spinal dorsal horn ameliorates neuropathic pain via cAMP-cytokine-Cx43 signaling in mice［J］. CNS Neurosci Ther， 2022， 28（5）： 749. |
| 27 | Xu F， Lv C， Deng Y， et al. Icariside Ⅱ， a PDE5 inhibitor， suppresses oxygen-glucose deprivation/reperfusion-induced primary hippocampal neuronal death through activating the PKG/CREB/BDNF/TrkB signaling pathway［J］. Front Pharmacol， 2020， 11： 523. |
| 28 | Shim YS， Pae CU， Cho KJ， et al. Effects of daily low-dose treatment with phosphodiesterase type 5 inhibitor on cognition， depression， somatization and erectile function in patients with erectile dysfunction： a double-blind， placebo-controlled study［J］. Int J Impot Res， 2014， 26（2）： 76. |
| 29 | Vieira MC， Monte FBM， Eduardo Dematte B， et al. Antinociceptive effect of lodenafil carbonate in rodent models of inflammatory pain and spinal nerve ligation-induced neuropathic pain［J］. J Pain Res， 2021， 14： 857. |
| 30 | Ch?oń-Rzepa G， ?lusarczyk M， Jankowska A， et al. Novel amide derivatives of 1，3-dimethyl-2，6-dioxopurin-7-yl-alkylcarboxylic acids as multifunctional TRPA1 antagonists and PDE4/7 inhibitors： a new approach for the treatment of pain［J］. Eur J Med Chem， 2018， 158： 517. |
| 31 | Huang XF， Jiang WT， Liu L， et al. A novel PDE9 inhibitor WYQ-C36D ameliorates corticosterone-induced neurotoxicity and depression-like behaviors by cGMP-CREB-related signaling［J］. CNS Neurosci Ther， 2018， 24（10）： 889. |
| 32 | Langen B， Dost R， Egerland U， et al. Effect of PDE10A inhibitors on MK-801-induced immobility in the forced swim test［J］. Psychopharmacology （Berl）， 2012， 221（2）： 249. |
| 33 | Luo HR， Wu GS， Dong C， et al. Association of PDE11A global haplotype with major depression and antidepressant drug response［J］. Neuropsychiatr Dis Treat， 2009， 5： 163. |
), 张婷2, 张汉霆1, 张芳芳1()","risUrl_cn":"//www.pitakata.com/xuebao/CN/article/getTxtFile.do?fileType=Ris&id=465","title_cn":"磷酸二酯酶在慢性疼痛与抑郁共病中的作用","doi":"10.3969/j.issn.2097-0005.2023.04.004","jieShuYe":"263","keywordList_en":["depression","chronic pain","phosphodiesterase"],"endNoteUrl_cn":"//www.pitakata.com/xuebao/CN/article/getTxtFile.do?fileType=EndNote&id=465","zhaiyao_en":"Chronic pain and depression are two major diseases that affect people's quality of life as well as their physical and mental health. Chronic pain is frequently accompanied by anxiety and depression and is associated with actual or potential tissue damage or described in terms of such damage. Depression is a central nervous system disorder characterized by significant and long-lasting depression or mood disorder， slow thinking， and decreased speech and movement and depression patients are more sensitive to pain. According to epidemiological research， the rate of comorbidity of chronic pain and depression is quite high， as is the rate of diagnosis and treatment. Phosphodiesterase （PDEs） is the only hydrolase responsible for the inside-cell degradation of the second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate. According to recent research， PDEs can modulate chronic pain and depression. As a result， in this review， new evidence for the link between chronic pain and depression are presented， and the potential role of PDEs in chronic pain-depression comorbidity were also discussed.
","bibtexUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=BibTeX&id=465","abstractUrl_cn":"http://xuebao.sdfmu.edu.cn/CN/10.3969/j.issn.2097-0005.2023.04.004","zuoZheCn_L":"陈世才, 张婷, 张汉霆, 张芳芳","juanUrl_cn":"http://xuebao.sdfmu.edu.cn/CN/Y2023","lanMu_en":"Pharmacology","qiUrl_en":"//www.pitakata.com/xuebao/EN/Y2023/V44/I4","zuoZhe_EN":"Shicai CHEN1(), Ting ZHANG2, Wenqing ZHENG1, Xiaoqian LIU1()","risUrl_en":"http://xuebao.sdfmu.edu.cn/EN/article/getTxtFile.do?fileType=Ris&id=465","title_en":"The involvement of phosphodiesterase in comorbidity of chronic pain and depression","hasPdf":"true"},"authorNotes_cn":["陈世才，硕士研究生，研究方向：慢性疼痛与抑郁共病的机制，E-mail：1569471045@qq.com。","张芳芳，博士，讲师，硕士研究生导师，研究方向：神经精神药理学，E-mail：15650512848@163.com。
The involvement of phosphodiesterase in comorbidity of chronic pain and depression
Shicai CHEN, Ting ZHANG, Wenqing ZHENG, Xiaoqian LIU
Journal of ShanDong First Medical University&ShanDong Academy of Medical Sciences››2023, Vol. 44››Issue (4): 260-263.
PDF(428 KB)
PDF(428 KB)
The involvement of phosphodiesterase in comorbidity of chronic pain and depression
Chronic pain and depression are two major diseases that affect people's quality of life as well as their physical and mental health. Chronic pain is frequently accompanied by anxiety and depression and is associated with actual or potential tissue damage or described in terms of such damage. Depression is a central nervous system disorder characterized by significant and long-lasting depression or mood disorder， slow thinking， and decreased speech and movement and depression patients are more sensitive to pain. According to epidemiological research， the rate of comorbidity of chronic pain and depression is quite high， as is the rate of diagnosis and treatment. Phosphodiesterase （PDEs） is the only hydrolase responsible for the inside-cell degradation of the second messengers cyclic adenosine monophosphate and cyclic guanosine monophosphate. According to recent research， PDEs can modulate chronic pain and depression. As a result， in this review， new evidence for the link between chronic pain and depression are presented， and the potential role of PDEs in chronic pain-depression comorbidity were also discussed.
| 1 | Huang X， Xiaokaiti Y， Yang J， et al. Inhibition of phosphodiesterase 2 reverses gp91phox oxidase-mediated depression- and anxiety-like behavior［J］. Neuropharmacology， 2018， 143： 176. |
| 2 | Wang H， Zhang FF， Xu Y， et al. The phosphodiesterase-4 inhibitor roflumilast， a potential treatment for the comorbidity of memory loss and depression in alzheimer's disease： a preclinical study in APP/PS1 transgenic mice［J］. Int J Neuropsychopharmacol， 2020， 23（10）： 700. |
| 3 | Kruse LS， Sandholdt NT， Gammeltoft S， et al. Phosphodiesterase 3 and 5 and cyclic nucleotide-gated ion channel expression in rat trigeminovascular system［J］. Neurosci Lett， 2006， 404（1/2）： 202. |
| 4 | Jankowska A， Sata?a G， Ko?aczkowski M， et al. Novel anilide and benzylamide derivatives of arylpiperazinylalkanoic acids as 5-HT1A/5-HT7 receptor antagonists and phosphodiesterase 4/7 inhibitors with procognitive and antidepressant activity［J］. Eur J Med Chem， 2020， 201： 112437. |
| 5 | 宋学军， 樊碧发， 万有， 等. 国际疼痛学会新版疼痛定义修订简析［J］. 中国疼痛医学杂志， 2020， 26（9）： 641. |
| 6 | Ohayon MM， Schatzberg AF. Chronic pain and major depressive disorder in the general population［J］. J Psychiatr Res， 2010， 44（7）： 454. |
| 7 | 徐子尧， 黄亚玲， 朱光强， 等. 中国青少年抑郁症患者非自杀性自伤行为发生率的Meta分析［J］. 四川精神卫生， 2022， 35（4）： 331. |
| 8 | Arango-Dávila CA， Rincón-Hoyos HG. Depressive disorder， anxiety disorder and chronic pain： multiple manifestations of a common clinical and pathophysiological core［J］. Rev Colomb Psiquiatr （Engl Ed）， 2018， 47（1）： 46. |
| 9 | 史妙， 王锦琰， 罗非. 疼痛和抑郁［J］. 中国药物与临床， 2009， 9（9）： 789. |
| 10 | Liu YT， Shao YW， Yen CT， et al. Acid-induced hyperalgesia and anxio-depressive comorbidity in rats［J］. Physiol Behav， 2014， 131： 105. |
| 11 | Boadas-Vaello P， Homs J， Portero-Tresserra M， et al. Graded photochemical spinal cord injury results in chronic hyperalgesia and depression-like behaviour but no anxiety exacerbation in female BALB/c mice［J］. Neurosci Lett， 2018， 664： 98. |
| 12 | Bura AS， Guegan T， Zamanillo D， et al. Operant self-administration of a sigma ligand improves nociceptive and emotional manifestations of neuropathic pain［J］. Eur J Pain， 2013， 17（6）： 832. |
| 13 | Li J， Li Y， Zhang B， et al. Why depression and pain often coexist and mutually reinforce： role of the lateral habenula［J］. Exp Neurol， 2016， 284（Pt A）： 106. |
| 14 | Burke NN， Finn DP， Roche M. Neuroinflammatory mechanisms linking pain and depression［J］. Mod Trends Pharmacopsychiatry， 2015， 30： 36. |
| 15 | Harth M， Nielson WR. Pain and affective distress in arthritis： relationship to immunity and inflammation［J］. Expert Rev Clin Immunol， 2019， 15（5）： 541. |
| 16 | Aroke EN， Joseph PV， Roy A， et al. Could epigenetics help explain racial disparities in chronic pain？［J］. J Pain Res， 2019， 12： 701. |
| 17 | Matthews SC， Strigo IA， Simmons AN， et al. Decreased functional coupling of the amygdala and supragenual cingulate is related to increased depression in unmedicated individuals with current major depressive disorder［J］. J Affect Disord， 2008， 111（1）： 13. |
| 18 | Delhaye S， Bardoni B. Role of phosphodiesterases in the pathophysiology of neurodevelopmental disorders［J］. Mol Psychiatry， 2021， 26（9）： 4570. |
| 19 | 严伟， 陈玲， 王飞， 等. 磷酸二酯酶2对抑郁焦虑及认知障碍等中枢神经疾病的调节作用［J］. 中国临床药理学与治疗学， 2013， 18（12）： 1424. |
| 20 | 徐江平， 汪海涛. 磷酸二酯酶4作为抗抑郁药物作用靶点的研究［J］. 遵义医学院学报， 2014， 37（5）： 449. |
| 21 | Plummer MS， Cornicelli J， Roark H， et al. Discovery of potent， selective， bioavailable phosphodiesterase 2 （PDE2） inhibitors active in an osteoarthritis pain model， part Ⅰ： transformation of selective pyrazolodiazepinone phosphodiesterase 4 （PDE4） inhibitors into selective PDE2 inhibitors［J］. Bioorg Med Chem Lett， 2013， 23（11）： 3438. |
| 22 | Wang JN， Zhao XJ， Liu ZH， et al. Selective phosphodiesterase-2A inhibitor alleviates radicular inflammation and mechanical allodynia in non-compressive lumbar disc herniation rats［J］. Eur Spine J， 2017， 26（7）： 1961. |
| 23 | 文睿婷， 张汉霆， 冯婉玉， 等. 磷酸二酯酶-4的中枢功能研究进展［J］. 中国药理学通报， 2014， 30（4）： 452. |
| 24 | Zhu X， Li W， Li Y， et al. The antidepressant- and anxiolytic-like effects of resveratrol： involvement of phosphodiesterase-4D inhibition［J］. Neuropharmacology， 2019， 153： 20. |
| 25 | 底妍， 和晓韵， 嵇睛， 等. 鞘内注射PDE4B-siRNA对L5脊神经结扎大鼠痛觉高敏的影响［J］. 临床麻醉学杂志， 2013， 29（6）： 604. |
| 26 | Zhang FF， Wang H， Zhou YM， et al. Inhibition of phosphodiesterase-4 in the spinal dorsal horn ameliorates neuropathic pain via cAMP-cytokine-Cx43 signaling in mice［J］. CNS Neurosci Ther， 2022， 28（5）： 749. |
| 27 | Xu F， Lv C， Deng Y， et al. Icariside Ⅱ， a PDE5 inhibitor， suppresses oxygen-glucose deprivation/reperfusion-induced primary hippocampal neuronal death through activating the PKG/CREB/BDNF/TrkB signaling pathway［J］. Front Pharmacol， 2020， 11： 523. |
| 28 | Shim YS， Pae CU， Cho KJ， et al. Effects of daily low-dose treatment with phosphodiesterase type 5 inhibitor on cognition， depression， somatization and erectile function in patients with erectile dysfunction： a double-blind， placebo-controlled study［J］. Int J Impot Res， 2014， 26（2）： 76. |
| 29 | Vieira MC， Monte FBM， Eduardo Dematte B， et al. Antinociceptive effect of lodenafil carbonate in rodent models of inflammatory pain and spinal nerve ligation-induced neuropathic pain［J］. J Pain Res， 2021， 14： 857. |
| 30 | Ch?oń-Rzepa G， ?lusarczyk M， Jankowska A， et al. Novel amide derivatives of 1，3-dimethyl-2，6-dioxopurin-7-yl-alkylcarboxylic acids as multifunctional TRPA1 antagonists and PDE4/7 inhibitors： a new approach for the treatment of pain［J］. Eur J Med Chem， 2018， 158： 517. |
| 31 | Huang XF， Jiang WT， Liu L， et al. A novel PDE9 inhibitor WYQ-C36D ameliorates corticosterone-induced neurotoxicity and depression-like behaviors by cGMP-CREB-related signaling［J］. CNS Neurosci Ther， 2018， 24（10）： 889. |
| 32 | Langen B， Dost R， Egerland U， et al. Effect of PDE10A inhibitors on MK-801-induced immobility in the forced swim test［J］. Psychopharmacology （Berl）， 2012， 221（2）： 249. |
| 33 | Luo HR， Wu GS， Dong C， et al. Association of PDE11A global haplotype with major depression and antidepressant drug response［J］. Neuropsychiatr Dis Treat， 2009， 5： 163. |
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