Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain
Although bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4) plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the...
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| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2015-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2015/523896 |
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| author | Ruirui Pan Huiting Di Jinming Zhang Zhangxiang Huang Yuming Sun Weifeng Yu Feixiang Wu |
| author_facet | Ruirui Pan Huiting Di Jinming Zhang Zhangxiang Huang Yuming Sun Weifeng Yu Feixiang Wu |
| author_sort | Ruirui Pan |
| collection | DOAJ |
| description | Although bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4) plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the downregulation of TLR4 by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for bone cancer pain, an inducible lentivirus LvOn-siTLR4 (tetracycline inducible lentivirus carrying siRNA targeting TLR4) was prepared and the antinociception effects were observed in bone cancer pain rats induced by Walker 256 cells injection in left leg. Results showed that LvOn-siTLR4 intrathecal injection with doxycycline (Dox) oral administration effectively reduced the nociception induced by Walker 256 cells while inhibiting the mRNA and protein expression of TLR4. Proinflammatory cytokines as TNF-α and IL-1β in spinal cord were also decreased. These findings suggest that TLR4 could be a target for bone cancer pain treatment and tetracycline inducible lentivirus LvOn-siTLR4 represents a new potential option for long-term treatment of bone cancer pain. |
| format | Article |
| id | doaj-art-28de1847c47c444fae32dc865fcb7729 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2015-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-28de1847c47c444fae32dc865fcb77292025-02-03T05:50:46ZengWileyMediators of Inflammation0962-93511466-18612015-01-01201510.1155/2015/523896523896Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer PainRuirui Pan0Huiting Di1Jinming Zhang2Zhangxiang Huang3Yuming Sun4Weifeng Yu5Feixiang Wu6Department of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, ChinaDepartment of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, ChinaDepartment of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, ChinaDepartment of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, ChinaDepartment of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, ChinaDepartment of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, ChinaDepartment of Anesthesiology, Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, ChinaAlthough bone cancer pain is still not fully understood by scientists and clinicians alike, studies suggest that toll like receptor 4 (TLR4) plays an important role in the initiation and/or maintenance of pathological pain state in bone cancer pain. A promising treatment for bone cancer pain is the downregulation of TLR4 by RNA interference; however, naked siRNA (small interference RNA) is not effective in long-term treatments. In order to concoct a viable prolonged treatment for bone cancer pain, an inducible lentivirus LvOn-siTLR4 (tetracycline inducible lentivirus carrying siRNA targeting TLR4) was prepared and the antinociception effects were observed in bone cancer pain rats induced by Walker 256 cells injection in left leg. Results showed that LvOn-siTLR4 intrathecal injection with doxycycline (Dox) oral administration effectively reduced the nociception induced by Walker 256 cells while inhibiting the mRNA and protein expression of TLR4. Proinflammatory cytokines as TNF-α and IL-1β in spinal cord were also decreased. These findings suggest that TLR4 could be a target for bone cancer pain treatment and tetracycline inducible lentivirus LvOn-siTLR4 represents a new potential option for long-term treatment of bone cancer pain.http://dx.doi.org/10.1155/2015/523896 |
| spellingShingle | Ruirui Pan Huiting Di Jinming Zhang Zhangxiang Huang Yuming Sun Weifeng Yu Feixiang Wu Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain Mediators of Inflammation |
| title | Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain |
| title_full | Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain |
| title_fullStr | Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain |
| title_full_unstemmed | Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain |
| title_short | Inducible Lentivirus-Mediated siRNA against TLR4 Reduces Nociception in a Rat Model of Bone Cancer Pain |
| title_sort | inducible lentivirus mediated sirna against tlr4 reduces nociception in a rat model of bone cancer pain |
| url | http://dx.doi.org/10.1155/2015/523896 |
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