Probucol is anti-hyperalgesic in a mouse peripheral nerve injury model of neuropathic pain
2,6-di-tert-butylphenol (2,6-DTBP) ameliorates mechanical allodynia and thermal hyperalgesia produced by partial sciatic nerve ligation in mice, and selectively inhibits HCN1 channel gating. We hypothesized that the clinically utilized non-anesthetic dimerized congener of 2,6-DTBP, probucol (2,6-di-...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-08-01
|
| Series: | Neurobiology of Pain |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452073X23000284 |
| _version_ | 1797405358247903232 |
|---|---|
| author | Rebecca L. Joyce Gareth R. Tibbs J. David Warren Christopher J. Costa Kelly Aromolaran R. Lea Sanford Olaf S. Andersen Zhucui Li Guoan Zhang Dianna E. Willis Peter A. Goldstein |
| author_facet | Rebecca L. Joyce Gareth R. Tibbs J. David Warren Christopher J. Costa Kelly Aromolaran R. Lea Sanford Olaf S. Andersen Zhucui Li Guoan Zhang Dianna E. Willis Peter A. Goldstein |
| author_sort | Rebecca L. Joyce |
| collection | DOAJ |
| description | 2,6-di-tert-butylphenol (2,6-DTBP) ameliorates mechanical allodynia and thermal hyperalgesia produced by partial sciatic nerve ligation in mice, and selectively inhibits HCN1 channel gating. We hypothesized that the clinically utilized non-anesthetic dimerized congener of 2,6-DTBP, probucol (2,6-di-tert-butyl-4-[2-(3,5-di-tert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenol), would relieve the neuropathic phenotype that results from peripheral nerve damage, and that the anti-hyperalgesic efficacy in vivo would correlate with HCN1 channel inhibition in vitro. A single oral dose of probucol (800 mg/kg) relieved mechanical allodynia and thermal hyperalgesia in a mouse spared-nerve injury neuropathic pain model. While the low aqueous solubility of probucol precluded assessment of its possible interaction with HCN1 channels, our results, in conjunction with recent data demonstrating that probucol reduces lipopolysaccharide-induced mechanical allodynia and thermal hyperalgesia, support the testing/development of probucol as a non-opioid, oral antihyperalgesic albeit one of unknown mechanistic action. |
| first_indexed | 2024-03-09T03:08:49Z |
| format | Article |
| id | doaj.art-32cd11e9aa564ac7b45c089bb33d5df1 |
| institution | Directory Open Access Journal |
| issn | 2452-073X |
| language | English |
| last_indexed | 2024-03-09T03:08:49Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Pain |
| spelling | doaj.art-32cd11e9aa564ac7b45c089bb33d5df12023-12-04T05:23:44ZengElsevierNeurobiology of Pain2452-073X2023-08-0114100141Probucol is anti-hyperalgesic in a mouse peripheral nerve injury model of neuropathic painRebecca L. Joyce0Gareth R. Tibbs1J. David Warren2Christopher J. Costa3Kelly Aromolaran4R. Lea Sanford5Olaf S. Andersen6Zhucui Li7Guoan Zhang8Dianna E. Willis9Peter A. Goldstein10Dept. of Anesthesiology, 1300 York Ave., Weill Cornell Medicine, New York, NY, USADept. of Anesthesiology, 1300 York Ave., Weill Cornell Medicine, New York, NY, USADept. of Biochemistry, 413 E. 69th Street, Weill Cornell Medicine, New York, NY, USABurke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY, USADept. of Anesthesiology, 1300 York Ave., Weill Cornell Medicine, New York, NY, USADept. of Physiology & Biophysics, 1300 York Ave., Weill Cornell Medicine, New York, NY, USADept. of Physiology & Biophysics, 1300 York Ave., Weill Cornell Medicine, New York, NY, USADept. of Biochemistry, 413 E. 69th Street, Weill Cornell Medicine, New York, NY, USADept. of Biochemistry, 413 E. 69th Street, Weill Cornell Medicine, New York, NY, USABurke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, NY, USA; Corresponding authors at: Dept. of Anesthesiology, Weill Cornell Medicine, 1300 York Avenue, Room A-1050, New York, NY 10065, USA (P.A. Goldstein). Burke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA (D.E. Willis).Dept. of Anesthesiology, 1300 York Ave., Weill Cornell Medicine, New York, NY, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, NY, USA; Dept. of Medicine, Weill Cornell Medicine, New York, NY, USA; Corresponding authors at: Dept. of Anesthesiology, Weill Cornell Medicine, 1300 York Avenue, Room A-1050, New York, NY 10065, USA (P.A. Goldstein). Burke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA (D.E. Willis).2,6-di-tert-butylphenol (2,6-DTBP) ameliorates mechanical allodynia and thermal hyperalgesia produced by partial sciatic nerve ligation in mice, and selectively inhibits HCN1 channel gating. We hypothesized that the clinically utilized non-anesthetic dimerized congener of 2,6-DTBP, probucol (2,6-di-tert-butyl-4-[2-(3,5-di-tert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenol), would relieve the neuropathic phenotype that results from peripheral nerve damage, and that the anti-hyperalgesic efficacy in vivo would correlate with HCN1 channel inhibition in vitro. A single oral dose of probucol (800 mg/kg) relieved mechanical allodynia and thermal hyperalgesia in a mouse spared-nerve injury neuropathic pain model. While the low aqueous solubility of probucol precluded assessment of its possible interaction with HCN1 channels, our results, in conjunction with recent data demonstrating that probucol reduces lipopolysaccharide-induced mechanical allodynia and thermal hyperalgesia, support the testing/development of probucol as a non-opioid, oral antihyperalgesic albeit one of unknown mechanistic action.http://www.sciencedirect.com/science/article/pii/S2452073X23000284Anti-hyperalgesiaAlkylphenolHCN1Ion channelSpared nerve injury |
| spellingShingle | Rebecca L. Joyce Gareth R. Tibbs J. David Warren Christopher J. Costa Kelly Aromolaran R. Lea Sanford Olaf S. Andersen Zhucui Li Guoan Zhang Dianna E. Willis Peter A. Goldstein Probucol is anti-hyperalgesic in a mouse peripheral nerve injury model of neuropathic pain Neurobiology of Pain Anti-hyperalgesia Alkylphenol HCN1 Ion channel Spared nerve injury |
| title | Probucol is anti-hyperalgesic in a mouse peripheral nerve injury model of neuropathic pain |
| title_full | Probucol is anti-hyperalgesic in a mouse peripheral nerve injury model of neuropathic pain |
| title_fullStr | Probucol is anti-hyperalgesic in a mouse peripheral nerve injury model of neuropathic pain |
| title_full_unstemmed | Probucol is anti-hyperalgesic in a mouse peripheral nerve injury model of neuropathic pain |
| title_short | Probucol is anti-hyperalgesic in a mouse peripheral nerve injury model of neuropathic pain |
| title_sort | probucol is anti hyperalgesic in a mouse peripheral nerve injury model of neuropathic pain |
| topic | Anti-hyperalgesia Alkylphenol HCN1 Ion channel Spared nerve injury |
| url | http://www.sciencedirect.com/science/article/pii/S2452073X23000284 |
| work_keys_str_mv | AT rebeccaljoyce probucolisantihyperalgesicinamouseperipheralnerveinjurymodelofneuropathicpain AT garethrtibbs probucolisantihyperalgesicinamouseperipheralnerveinjurymodelofneuropathicpain AT jdavidwarren probucolisantihyperalgesicinamouseperipheralnerveinjurymodelofneuropathicpain AT christopherjcosta probucolisantihyperalgesicinamouseperipheralnerveinjurymodelofneuropathicpain AT kellyaromolaran probucolisantihyperalgesicinamouseperipheralnerveinjurymodelofneuropathicpain AT rleasanford probucolisantihyperalgesicinamouseperipheralnerveinjurymodelofneuropathicpain AT olafsandersen probucolisantihyperalgesicinamouseperipheralnerveinjurymodelofneuropathicpain AT zhucuili probucolisantihyperalgesicinamouseperipheralnerveinjurymodelofneuropathicpain AT guoanzhang probucolisantihyperalgesicinamouseperipheralnerveinjurymodelofneuropathicpain AT diannaewillis probucolisantihyperalgesicinamouseperipheralnerveinjurymodelofneuropathicpain AT peteragoldstein probucolisantihyperalgesicinamouseperipheralnerveinjurymodelofneuropathicpain |