Overexpression of GDNF in Spinal Cord Attenuates Morphine Analgesic Tolerance in Rats with Bone Cancer Pain
Bone cancer pain (BCP) is one of the typical and distressing symptoms in cancer patients. Morphine is a widely used analgesic drug for BCP; however, long-term morphine administration will lead to analgesic tolerance. Our previous study indicated that spinal glial cell line-derived neurotrophic facto...
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MDPI AG
2022-09-01
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| Series: | Brain Sciences |
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| Online Access: | https://www.mdpi.com/2076-3425/12/9/1188 |
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| author | Wei Xu Zhuofeng Ding Zongbin Song Jian Wang Jie Zhang Wangyuan Zou |
| author_facet | Wei Xu Zhuofeng Ding Zongbin Song Jian Wang Jie Zhang Wangyuan Zou |
| author_sort | Wei Xu |
| collection | DOAJ |
| description | Bone cancer pain (BCP) is one of the typical and distressing symptoms in cancer patients. Morphine is a widely used analgesic drug for BCP; however, long-term morphine administration will lead to analgesic tolerance. Our previous study indicated that spinal glial cell line-derived neurotrophic factor (GDNF) exerts analgesic effects in rats with BCP. In this study, BCP was established by inoculated Walker 256 carcinoma cells into rat tibias, while morphine tolerance (MT) was induced by intrathecally injecting morphine twice daily from the 9th to 15th postoperative day (POD) in BCP rats. The BCP rats developed mechanical and thermal hyperalgesia on POD 5 and it lasted to POD 15. The analgesic effect of morphine was decreased after repeat administration. Western blots and immunochemistry tests showed that GDNF was gradually decreased in the spinal cord after the development of MT in rats with BCP, and GDNF was colocalized with the μ opioid receptor (MOR) in the superficial laminate of the spinal cords. The overexpression of GDNF by lentivirus significantly attenuated MT, and restored the expression of MOR in the spinal cord. In summary, our results suggest that the reduction of GDNF expression participated in the development of MT in rats with BCP and could be a promising therapeutic option for BCP. |
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| language | English |
| last_indexed | 2024-03-10T00:33:56Z |
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| spelling | doaj.art-ec29298dcf24478eb9ceb300103cfc992023-11-23T15:20:43ZengMDPI AGBrain Sciences2076-34252022-09-01129118810.3390/brainsci12091188Overexpression of GDNF in Spinal Cord Attenuates Morphine Analgesic Tolerance in Rats with Bone Cancer PainWei Xu0Zhuofeng Ding1Zongbin Song2Jian Wang3Jie Zhang4Wangyuan Zou5Department of Anesthesiology, The Maternal and Child Health Hospital of Hunan Province, Changsha 410010, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of Anesthesiology, The Maternal and Child Health Hospital of Hunan Province, Changsha 410010, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha 410008, ChinaBone cancer pain (BCP) is one of the typical and distressing symptoms in cancer patients. Morphine is a widely used analgesic drug for BCP; however, long-term morphine administration will lead to analgesic tolerance. Our previous study indicated that spinal glial cell line-derived neurotrophic factor (GDNF) exerts analgesic effects in rats with BCP. In this study, BCP was established by inoculated Walker 256 carcinoma cells into rat tibias, while morphine tolerance (MT) was induced by intrathecally injecting morphine twice daily from the 9th to 15th postoperative day (POD) in BCP rats. The BCP rats developed mechanical and thermal hyperalgesia on POD 5 and it lasted to POD 15. The analgesic effect of morphine was decreased after repeat administration. Western blots and immunochemistry tests showed that GDNF was gradually decreased in the spinal cord after the development of MT in rats with BCP, and GDNF was colocalized with the μ opioid receptor (MOR) in the superficial laminate of the spinal cords. The overexpression of GDNF by lentivirus significantly attenuated MT, and restored the expression of MOR in the spinal cord. In summary, our results suggest that the reduction of GDNF expression participated in the development of MT in rats with BCP and could be a promising therapeutic option for BCP.https://www.mdpi.com/2076-3425/12/9/1188bone cancer painmorphine toleranceglial cell line-derived neurotrophic factorMORspinal |
| spellingShingle | Wei Xu Zhuofeng Ding Zongbin Song Jian Wang Jie Zhang Wangyuan Zou Overexpression of GDNF in Spinal Cord Attenuates Morphine Analgesic Tolerance in Rats with Bone Cancer Pain Brain Sciences bone cancer pain morphine tolerance glial cell line-derived neurotrophic factor MOR spinal |
| title | Overexpression of GDNF in Spinal Cord Attenuates Morphine Analgesic Tolerance in Rats with Bone Cancer Pain |
| title_full | Overexpression of GDNF in Spinal Cord Attenuates Morphine Analgesic Tolerance in Rats with Bone Cancer Pain |
| title_fullStr | Overexpression of GDNF in Spinal Cord Attenuates Morphine Analgesic Tolerance in Rats with Bone Cancer Pain |
| title_full_unstemmed | Overexpression of GDNF in Spinal Cord Attenuates Morphine Analgesic Tolerance in Rats with Bone Cancer Pain |
| title_short | Overexpression of GDNF in Spinal Cord Attenuates Morphine Analgesic Tolerance in Rats with Bone Cancer Pain |
| title_sort | overexpression of gdnf in spinal cord attenuates morphine analgesic tolerance in rats with bone cancer pain |
| topic | bone cancer pain morphine tolerance glial cell line-derived neurotrophic factor MOR spinal |
| url | https://www.mdpi.com/2076-3425/12/9/1188 |
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