Resolvin D2 Reduces Chronic Neuropathic Pain and Bone Cancer Pain via Spinal Inhibition of IL-17 Secretion, CXCL1 Release and Astrocyte Activation in Mice
Chronic pain burdens patients and healthcare systems worldwide. Pain control remains urgently required. IL-17 (interleukin-17)-mediated neuroinflammation is of unique importance in spinal nociceptive transduction in pathological pain development. Recently, resolvin D2 (RvD2), as a bioactive, special...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/13/1/152 |
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| author | Jun Pang Pengfei Xin Ying Kong Zhe Wang Xiaopeng Wang |
| author_facet | Jun Pang Pengfei Xin Ying Kong Zhe Wang Xiaopeng Wang |
| author_sort | Jun Pang |
| collection | DOAJ |
| description | Chronic pain burdens patients and healthcare systems worldwide. Pain control remains urgently required. IL-17 (interleukin-17)-mediated neuroinflammation is of unique importance in spinal nociceptive transduction in pathological pain development. Recently, resolvin D2 (RvD2), as a bioactive, specialized pro-resolving mediator derived from docosahexaenoic acid, exhibits potent resolution of inflammation in several neurological disorders. This preclinical study evaluates the therapeutic potential and underlying targets of RvD2 in two mouse models of chronic pain, including sciatic nerve ligation-caused neuropathic pain and sarcoma-caused bone cancer pain. Herein, we report that repetitive injections of RvD2 (intrathecal, 500 ng) reduce the initiation of mechanical allodynia and heat hyperalgesia following sciatic nerve damage and bone cancer. Single exposure to RvD2 (intrathecal, 500 ng) attenuates the established neuropathic pain and bone cancer pain. Furthermore, systemic RvD2 (intravenous, 5 μg) therapy is effective in attenuating chronic pain behaviors. Strikingly, RvD2 treatment suppresses spinal IL-17 overexpression, chemokine CXCL1 release and astrocyte activation in mice undergoing sciatic nerve trauma and bone cancer. Pharmacological neutralization of IL-17 ameliorates chronic neuropathic pain and persistent bone cancer pain, as well as reducing spinal CXCL1 release. Recombinant IL-17-evoked acute pain behaviors and spinal CXCL1 release are mitigated after RvD2 administration. In addition, RvD2 treatment dampens exogenous CXCL1-caused transient pain phenotypes. Overall, these current findings identify that RvD2 therapy is effective against the initiation and persistence of long-lasting neuropathic pain and bone cancer pain, which may be through spinal down-modulation of IL-17 secretion, CXCL1 release and astrocyte activation. |
| first_indexed | 2024-03-09T13:22:31Z |
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| id | doaj.art-8a6731daf9b34492b2cef8ceb5b318a0 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-09T13:22:31Z |
| publishDate | 2023-01-01 |
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| series | Brain Sciences |
| spelling | doaj.art-8a6731daf9b34492b2cef8ceb5b318a02023-11-30T21:28:24ZengMDPI AGBrain Sciences2076-34252023-01-0113115210.3390/brainsci13010152Resolvin D2 Reduces Chronic Neuropathic Pain and Bone Cancer Pain via Spinal Inhibition of IL-17 Secretion, CXCL1 Release and Astrocyte Activation in MiceJun Pang0Pengfei Xin1Ying Kong2Zhe Wang3Xiaopeng Wang4Department of Anesthesiology & Center for Brain Science, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, ChinaTongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, ChinaDepartment of Anesthesiology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, ChinaDepartment of Anesthesiology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, ChinaDepartment of Anesthesiology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan 030032, ChinaChronic pain burdens patients and healthcare systems worldwide. Pain control remains urgently required. IL-17 (interleukin-17)-mediated neuroinflammation is of unique importance in spinal nociceptive transduction in pathological pain development. Recently, resolvin D2 (RvD2), as a bioactive, specialized pro-resolving mediator derived from docosahexaenoic acid, exhibits potent resolution of inflammation in several neurological disorders. This preclinical study evaluates the therapeutic potential and underlying targets of RvD2 in two mouse models of chronic pain, including sciatic nerve ligation-caused neuropathic pain and sarcoma-caused bone cancer pain. Herein, we report that repetitive injections of RvD2 (intrathecal, 500 ng) reduce the initiation of mechanical allodynia and heat hyperalgesia following sciatic nerve damage and bone cancer. Single exposure to RvD2 (intrathecal, 500 ng) attenuates the established neuropathic pain and bone cancer pain. Furthermore, systemic RvD2 (intravenous, 5 μg) therapy is effective in attenuating chronic pain behaviors. Strikingly, RvD2 treatment suppresses spinal IL-17 overexpression, chemokine CXCL1 release and astrocyte activation in mice undergoing sciatic nerve trauma and bone cancer. Pharmacological neutralization of IL-17 ameliorates chronic neuropathic pain and persistent bone cancer pain, as well as reducing spinal CXCL1 release. Recombinant IL-17-evoked acute pain behaviors and spinal CXCL1 release are mitigated after RvD2 administration. In addition, RvD2 treatment dampens exogenous CXCL1-caused transient pain phenotypes. Overall, these current findings identify that RvD2 therapy is effective against the initiation and persistence of long-lasting neuropathic pain and bone cancer pain, which may be through spinal down-modulation of IL-17 secretion, CXCL1 release and astrocyte activation.https://www.mdpi.com/2076-3425/13/1/152RvD2neuropathic painbone cancer painIL-17CXCL1astrocyte activation |
| spellingShingle | Jun Pang Pengfei Xin Ying Kong Zhe Wang Xiaopeng Wang Resolvin D2 Reduces Chronic Neuropathic Pain and Bone Cancer Pain via Spinal Inhibition of IL-17 Secretion, CXCL1 Release and Astrocyte Activation in Mice Brain Sciences RvD2 neuropathic pain bone cancer pain IL-17 CXCL1 astrocyte activation |
| title | Resolvin D2 Reduces Chronic Neuropathic Pain and Bone Cancer Pain via Spinal Inhibition of IL-17 Secretion, CXCL1 Release and Astrocyte Activation in Mice |
| title_full | Resolvin D2 Reduces Chronic Neuropathic Pain and Bone Cancer Pain via Spinal Inhibition of IL-17 Secretion, CXCL1 Release and Astrocyte Activation in Mice |
| title_fullStr | Resolvin D2 Reduces Chronic Neuropathic Pain and Bone Cancer Pain via Spinal Inhibition of IL-17 Secretion, CXCL1 Release and Astrocyte Activation in Mice |
| title_full_unstemmed | Resolvin D2 Reduces Chronic Neuropathic Pain and Bone Cancer Pain via Spinal Inhibition of IL-17 Secretion, CXCL1 Release and Astrocyte Activation in Mice |
| title_short | Resolvin D2 Reduces Chronic Neuropathic Pain and Bone Cancer Pain via Spinal Inhibition of IL-17 Secretion, CXCL1 Release and Astrocyte Activation in Mice |
| title_sort | resolvin d2 reduces chronic neuropathic pain and bone cancer pain via spinal inhibition of il 17 secretion cxcl1 release and astrocyte activation in mice |
| topic | RvD2 neuropathic pain bone cancer pain IL-17 CXCL1 astrocyte activation |
| url | https://www.mdpi.com/2076-3425/13/1/152 |
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