Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesia
Migraine is one of the most common pain disorders and causes disability in millions of people every year. Delta opioid receptors (DOR) have been identified as a novel therapeutic target for migraine and other headache disorders. DORs are present in both peripheral and central regions and it is uncle...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Neurobiology of Pain |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2452073X22000162 |
| _version_ | 1811187919779528704 |
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| author | Zachariah Bertels Isaac J. Dripps Pal Shah Laura S. Moye Alycia F. Tipton Kendra Siegersma Amynah A. Pradhan |
| author_facet | Zachariah Bertels Isaac J. Dripps Pal Shah Laura S. Moye Alycia F. Tipton Kendra Siegersma Amynah A. Pradhan |
| author_sort | Zachariah Bertels |
| collection | DOAJ |
| description | Migraine is one of the most common pain disorders and causes disability in millions of people every year. Delta opioid receptors (DOR) have been identified as a novel therapeutic target for migraine and other headache disorders. DORs are present in both peripheral and central regions and it is unclear which receptor populations regulate migraine-associated effects. The aim of this study was to determine if DOR expressed in peripheral nociceptors regulates headache associated endpoints and the effect of delta agonists within these mouse models. We used a conditional knockout, in which DOR was selectively deleted from Nav1.8 expressing cells. Nav1.8-DOR mice and loxP control littermates were tested in models of chronic migraine-associated allodynia, opioid-induced hyperalgesia, migraine-associated negative affect, and aura. Nav1.8-DOR and loxP mice had comparable effect sizes in all of these models. The anti-allodynic effect of the DOR agonist, SNC80, was slightly diminished in the nitroglycerin model of migraine. Intriguingly, in the OIH model the peripheral effects of SNC80 were completely lost in Nav1.8-DOR mice while the cephalic effects remained intact. Regardless of genotype, SNC80 continued to inhibit conditioned place aversion associated with nitroglycerin and decreased cortical spreading depression events associated with migraine aura. These results suggest that DOR in Nav1.8-expressing nociceptors do not critically regulate the anti-migraine effects of delta agonist; and that brain-penetrant delta agonists would be a more effective drug development strategy. |
| first_indexed | 2024-04-11T14:11:39Z |
| format | Article |
| id | doaj.art-b44729b7206341089a0216b39e2458d8 |
| institution | Directory Open Access Journal |
| issn | 2452-073X |
| language | English |
| last_indexed | 2024-04-11T14:11:39Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Pain |
| spelling | doaj.art-b44729b7206341089a0216b39e2458d82022-12-22T04:19:42ZengElsevierNeurobiology of Pain2452-073X2022-08-0112100099Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesiaZachariah Bertels0Isaac J. Dripps1Pal Shah2Laura S. Moye3Alycia F. Tipton4Kendra Siegersma5Amynah A. Pradhan6Department of Psychiatry, University of Illinois at Chicago, United StatesDepartment of Psychiatry, University of Illinois at Chicago, United StatesDepartment of Psychiatry, University of Illinois at Chicago, United StatesDepartment of Psychiatry, University of Illinois at Chicago, United StatesDepartment of Psychiatry, University of Illinois at Chicago, United StatesDepartment of Psychiatry, University of Illinois at Chicago, United StatesCorresponding author at: 1601 W. Taylor Street (MC 912), Chicago, IL 60612, United States.; Department of Psychiatry, University of Illinois at Chicago, United StatesMigraine is one of the most common pain disorders and causes disability in millions of people every year. Delta opioid receptors (DOR) have been identified as a novel therapeutic target for migraine and other headache disorders. DORs are present in both peripheral and central regions and it is unclear which receptor populations regulate migraine-associated effects. The aim of this study was to determine if DOR expressed in peripheral nociceptors regulates headache associated endpoints and the effect of delta agonists within these mouse models. We used a conditional knockout, in which DOR was selectively deleted from Nav1.8 expressing cells. Nav1.8-DOR mice and loxP control littermates were tested in models of chronic migraine-associated allodynia, opioid-induced hyperalgesia, migraine-associated negative affect, and aura. Nav1.8-DOR and loxP mice had comparable effect sizes in all of these models. The anti-allodynic effect of the DOR agonist, SNC80, was slightly diminished in the nitroglycerin model of migraine. Intriguingly, in the OIH model the peripheral effects of SNC80 were completely lost in Nav1.8-DOR mice while the cephalic effects remained intact. Regardless of genotype, SNC80 continued to inhibit conditioned place aversion associated with nitroglycerin and decreased cortical spreading depression events associated with migraine aura. These results suggest that DOR in Nav1.8-expressing nociceptors do not critically regulate the anti-migraine effects of delta agonist; and that brain-penetrant delta agonists would be a more effective drug development strategy.http://www.sciencedirect.com/science/article/pii/S2452073X22000162AllodyniaHeadache disordersMouseCortical spreading depression |
| spellingShingle | Zachariah Bertels Isaac J. Dripps Pal Shah Laura S. Moye Alycia F. Tipton Kendra Siegersma Amynah A. Pradhan Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesia Neurobiology of Pain Allodynia Headache disorders Mouse Cortical spreading depression |
| title | Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesia |
| title_full | Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesia |
| title_fullStr | Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesia |
| title_full_unstemmed | Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesia |
| title_short | Delta opioid receptors in Nav1.8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid-induced hyperalgesia |
| title_sort | delta opioid receptors in nav1 8 expressing peripheral neurons partially regulate the effect of delta agonist in models of migraine and opioid induced hyperalgesia |
| topic | Allodynia Headache disorders Mouse Cortical spreading depression |
| url | http://www.sciencedirect.com/science/article/pii/S2452073X22000162 |
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