The Microglial Activation Inhibitor Minocycline, Used Alone and in Combination with Duloxetine, Attenuates Pain Caused by Oxaliplatin in Mice
The antitumor drug, oxaliplatin, induces neuropathic pain, which is resistant to available analgesics, and novel mechanism-based therapies are being evaluated for this debilitating condition. Since activated microglia, impaired serotonergic and noradrenergic neurotransmission and overexpressed sodiu...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-06-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/26/12/3577 |
| _version_ | 1797530495492292608 |
|---|---|
| author | Kinga Sałat Anna Furgała-Wojas Robert Sałat |
| author_facet | Kinga Sałat Anna Furgała-Wojas Robert Sałat |
| author_sort | Kinga Sałat |
| collection | DOAJ |
| description | The antitumor drug, oxaliplatin, induces neuropathic pain, which is resistant to available analgesics, and novel mechanism-based therapies are being evaluated for this debilitating condition. Since activated microglia, impaired serotonergic and noradrenergic neurotransmission and overexpressed sodium channels are implicated in oxaliplatin-induced pain, this in vivo study assessed the effect of minocycline, a microglial activation inhibitor used alone or in combination with ambroxol, a sodium channel blocker, or duloxetine, a serotonin and noradrenaline reuptake inhibitor, on oxaliplatin-induced tactile allodynia and cold hyperalgesia. To induce neuropathic pain, a single dose (10 mg/kg) of intraperitoneal oxaliplatin was used. The mechanical and cold pain thresholds were assessed using mouse von Frey and cold plate tests, respectively. On the day of oxaliplatin administration, only duloxetine (30 mg/kg) and minocycline (100 mg/kg) used alone attenuated both tactile allodynia and cold hyperalgesia 1 h and 6 h after administration. Minocycline (50 mg/kg), duloxetine (10 mg/kg) and combined minocycline + duloxetine influenced only tactile allodynia. Seven days after oxaliplatin, tactile allodynia (but not cold hyperalgesia) was attenuated by minocycline (100 mg/kg), duloxetine (30 mg/kg) and combined minocycline and duloxetine. These results indicate a potential usefulness of minocycline used alone or combination with duloxetine in the treatment of oxaliplatin-induced pain. |
| first_indexed | 2024-03-10T10:29:48Z |
| format | Article |
| id | doaj.art-ef96d6b8b5c84eb7aefcf68abaced5d2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:29:48Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-ef96d6b8b5c84eb7aefcf68abaced5d22023-11-21T23:45:19ZengMDPI AGMolecules1420-30492021-06-012612357710.3390/molecules26123577The Microglial Activation Inhibitor Minocycline, Used Alone and in Combination with Duloxetine, Attenuates Pain Caused by Oxaliplatin in MiceKinga Sałat0Anna Furgała-Wojas1Robert Sałat2Department of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, PolandDepartment of Pharmacodynamics, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna St., 30-688 Krakow, PolandFaculty of Electrical and Computer Engineering, Cracow University of Technology, 24 Warszawska St., 31-155 Krakow, PolandThe antitumor drug, oxaliplatin, induces neuropathic pain, which is resistant to available analgesics, and novel mechanism-based therapies are being evaluated for this debilitating condition. Since activated microglia, impaired serotonergic and noradrenergic neurotransmission and overexpressed sodium channels are implicated in oxaliplatin-induced pain, this in vivo study assessed the effect of minocycline, a microglial activation inhibitor used alone or in combination with ambroxol, a sodium channel blocker, or duloxetine, a serotonin and noradrenaline reuptake inhibitor, on oxaliplatin-induced tactile allodynia and cold hyperalgesia. To induce neuropathic pain, a single dose (10 mg/kg) of intraperitoneal oxaliplatin was used. The mechanical and cold pain thresholds were assessed using mouse von Frey and cold plate tests, respectively. On the day of oxaliplatin administration, only duloxetine (30 mg/kg) and minocycline (100 mg/kg) used alone attenuated both tactile allodynia and cold hyperalgesia 1 h and 6 h after administration. Minocycline (50 mg/kg), duloxetine (10 mg/kg) and combined minocycline + duloxetine influenced only tactile allodynia. Seven days after oxaliplatin, tactile allodynia (but not cold hyperalgesia) was attenuated by minocycline (100 mg/kg), duloxetine (30 mg/kg) and combined minocycline and duloxetine. These results indicate a potential usefulness of minocycline used alone or combination with duloxetine in the treatment of oxaliplatin-induced pain.https://www.mdpi.com/1420-3049/26/12/3577oxaliplatin-induced neuropathic painminocyclinemicroglial inhibitionduloxetinecombination drug therapy |
| spellingShingle | Kinga Sałat Anna Furgała-Wojas Robert Sałat The Microglial Activation Inhibitor Minocycline, Used Alone and in Combination with Duloxetine, Attenuates Pain Caused by Oxaliplatin in Mice Molecules oxaliplatin-induced neuropathic pain minocycline microglial inhibition duloxetine combination drug therapy |
| title | The Microglial Activation Inhibitor Minocycline, Used Alone and in Combination with Duloxetine, Attenuates Pain Caused by Oxaliplatin in Mice |
| title_full | The Microglial Activation Inhibitor Minocycline, Used Alone and in Combination with Duloxetine, Attenuates Pain Caused by Oxaliplatin in Mice |
| title_fullStr | The Microglial Activation Inhibitor Minocycline, Used Alone and in Combination with Duloxetine, Attenuates Pain Caused by Oxaliplatin in Mice |
| title_full_unstemmed | The Microglial Activation Inhibitor Minocycline, Used Alone and in Combination with Duloxetine, Attenuates Pain Caused by Oxaliplatin in Mice |
| title_short | The Microglial Activation Inhibitor Minocycline, Used Alone and in Combination with Duloxetine, Attenuates Pain Caused by Oxaliplatin in Mice |
| title_sort | microglial activation inhibitor minocycline used alone and in combination with duloxetine attenuates pain caused by oxaliplatin in mice |
| topic | oxaliplatin-induced neuropathic pain minocycline microglial inhibition duloxetine combination drug therapy |
| url | https://www.mdpi.com/1420-3049/26/12/3577 |
| work_keys_str_mv | AT kingasałat themicroglialactivationinhibitorminocyclineusedaloneandincombinationwithduloxetineattenuatespaincausedbyoxaliplatininmice AT annafurgaławojas themicroglialactivationinhibitorminocyclineusedaloneandincombinationwithduloxetineattenuatespaincausedbyoxaliplatininmice AT robertsałat themicroglialactivationinhibitorminocyclineusedaloneandincombinationwithduloxetineattenuatespaincausedbyoxaliplatininmice AT kingasałat microglialactivationinhibitorminocyclineusedaloneandincombinationwithduloxetineattenuatespaincausedbyoxaliplatininmice AT annafurgaławojas microglialactivationinhibitorminocyclineusedaloneandincombinationwithduloxetineattenuatespaincausedbyoxaliplatininmice AT robertsałat microglialactivationinhibitorminocyclineusedaloneandincombinationwithduloxetineattenuatespaincausedbyoxaliplatininmice |