Analgesic Activity of Cinnabarinic Acid in Models of Inflammatory and Neuropathic Pain
Cinnabarinic acid (CA) is a trace kynurenine metabolite, which activates both type-4 metabotropic glutamate (mGlu4) and arylic hydrocarbon (Ah) receptors. We examined the action of CA in models of inflammatory and neuropathic pain moving from the evidence that mGlu4 receptors are involved in the reg...
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| Format: | Article |
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnmol.2022.892870/full |
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| author | Serena Notartomaso Serena Boccella N. Antenucci Flavia Ricciardi Francesco Fazio F. Liberatore P. Scarselli M. Scioli Giada Mascio V. Bruno V. Bruno Giuseppe Battaglia Giuseppe Battaglia Ferdinando Nicoletti Ferdinando Nicoletti Sabatino Maione Sabatino Maione Livio Luongo Livio Luongo |
| author_facet | Serena Notartomaso Serena Boccella N. Antenucci Flavia Ricciardi Francesco Fazio F. Liberatore P. Scarselli M. Scioli Giada Mascio V. Bruno V. Bruno Giuseppe Battaglia Giuseppe Battaglia Ferdinando Nicoletti Ferdinando Nicoletti Sabatino Maione Sabatino Maione Livio Luongo Livio Luongo |
| author_sort | Serena Notartomaso |
| collection | DOAJ |
| description | Cinnabarinic acid (CA) is a trace kynurenine metabolite, which activates both type-4 metabotropic glutamate (mGlu4) and arylic hydrocarbon (Ah) receptors. We examined the action of CA in models of inflammatory and neuropathic pain moving from the evidence that mGlu4 receptors are involved in the regulation of pain thresholds. Systemic administration of low doses of CA (0.125 and 0.25 mg/kg, i.p.) reduced nocifensive behaviour in the second phase of the formalin test. CA-induced analgesia was abrogated in mGlu4 receptor knockout mice, but was unaffected by treatment with the Ah receptor antagonist, CH223191 (1 mg/Kg, s.c.). Acute injection of low doses of CA (0.25 mg/kg, i.p.) also caused analgesia in mice subjected to Chronic Constriction Injury (CCI) of the sciatic nerve. Electrophysiological recording showed no effect of CA on spinal cord nociceptive neurons and a trend to a lowering effect on the frequency and duration of excitation of the rostral ventromedial medulla (RVM) ON cells in CCI mice. However, local application of CH223191 or the group-III mGlu receptor antagonist, MSOP disclosed a substantial lowering and enhancing effect of CA on both populations of neurons, respectively. When repeatedly administered to CCI mice, CA retained the analgesic activity only when combined with CH223191. Repeated administration of CA plus CH223191 restrained the activity of both spinal nociceptive neurons and RVM ON cells, in full agreement with the analgesic activity. These findings suggest that CA is involved in the regulation of pain transmission, and its overall effect depends on the recruitment of mGlu4 and Ah receptors. |
| first_indexed | 2024-12-11T18:00:38Z |
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| id | doaj.art-d2a42c5aabdb496ca06d4339c75ed2a4 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-11T18:00:38Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-d2a42c5aabdb496ca06d4339c75ed2a42022-12-22T00:55:53ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992022-06-011510.3389/fnmol.2022.892870892870Analgesic Activity of Cinnabarinic Acid in Models of Inflammatory and Neuropathic PainSerena Notartomaso0Serena Boccella1N. Antenucci2Flavia Ricciardi3Francesco Fazio4F. Liberatore5P. Scarselli6M. Scioli7Giada Mascio8V. Bruno9V. Bruno10Giuseppe Battaglia11Giuseppe Battaglia12Ferdinando Nicoletti13Ferdinando Nicoletti14Sabatino Maione15Sabatino Maione16Livio Luongo17Livio Luongo18Department of Molecular Pathology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, ItalyDepartment of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, Rome, ItalyDepartment of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, ItalyDepartment of Psychiatry and Health Science, University of California, San Diego, La Jolla, CA, United StatesDepartment of Molecular Pathology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, ItalyDepartment of Molecular Pathology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, ItalyDepartment of Molecular Pathology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, ItalyDepartment of Molecular Pathology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, ItalyDepartment of Molecular Pathology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Pathology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, Rome, ItalyDepartment of Molecular Pathology, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, ItalyDepartment of Physiology and Pharmacology, Sapienza University of Rome, Rome, ItalyDepartment of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, ItalyIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, ItalyDepartment of Experimental Medicine, University of Campania Luigi Vanvitelli, Naples, ItalyIstituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Neuromed, Pozzilli, ItalyCinnabarinic acid (CA) is a trace kynurenine metabolite, which activates both type-4 metabotropic glutamate (mGlu4) and arylic hydrocarbon (Ah) receptors. We examined the action of CA in models of inflammatory and neuropathic pain moving from the evidence that mGlu4 receptors are involved in the regulation of pain thresholds. Systemic administration of low doses of CA (0.125 and 0.25 mg/kg, i.p.) reduced nocifensive behaviour in the second phase of the formalin test. CA-induced analgesia was abrogated in mGlu4 receptor knockout mice, but was unaffected by treatment with the Ah receptor antagonist, CH223191 (1 mg/Kg, s.c.). Acute injection of low doses of CA (0.25 mg/kg, i.p.) also caused analgesia in mice subjected to Chronic Constriction Injury (CCI) of the sciatic nerve. Electrophysiological recording showed no effect of CA on spinal cord nociceptive neurons and a trend to a lowering effect on the frequency and duration of excitation of the rostral ventromedial medulla (RVM) ON cells in CCI mice. However, local application of CH223191 or the group-III mGlu receptor antagonist, MSOP disclosed a substantial lowering and enhancing effect of CA on both populations of neurons, respectively. When repeatedly administered to CCI mice, CA retained the analgesic activity only when combined with CH223191. Repeated administration of CA plus CH223191 restrained the activity of both spinal nociceptive neurons and RVM ON cells, in full agreement with the analgesic activity. These findings suggest that CA is involved in the regulation of pain transmission, and its overall effect depends on the recruitment of mGlu4 and Ah receptors.https://www.frontiersin.org/articles/10.3389/fnmol.2022.892870/fullanalgesianeuropathic paincinnabarinic acidmetabotropic glutamate receptor 4inflammatory pain |
| spellingShingle | Serena Notartomaso Serena Boccella N. Antenucci Flavia Ricciardi Francesco Fazio F. Liberatore P. Scarselli M. Scioli Giada Mascio V. Bruno V. Bruno Giuseppe Battaglia Giuseppe Battaglia Ferdinando Nicoletti Ferdinando Nicoletti Sabatino Maione Sabatino Maione Livio Luongo Livio Luongo Analgesic Activity of Cinnabarinic Acid in Models of Inflammatory and Neuropathic Pain Frontiers in Molecular Neuroscience analgesia neuropathic pain cinnabarinic acid metabotropic glutamate receptor 4 inflammatory pain |
| title | Analgesic Activity of Cinnabarinic Acid in Models of Inflammatory and Neuropathic Pain |
| title_full | Analgesic Activity of Cinnabarinic Acid in Models of Inflammatory and Neuropathic Pain |
| title_fullStr | Analgesic Activity of Cinnabarinic Acid in Models of Inflammatory and Neuropathic Pain |
| title_full_unstemmed | Analgesic Activity of Cinnabarinic Acid in Models of Inflammatory and Neuropathic Pain |
| title_short | Analgesic Activity of Cinnabarinic Acid in Models of Inflammatory and Neuropathic Pain |
| title_sort | analgesic activity of cinnabarinic acid in models of inflammatory and neuropathic pain |
| topic | analgesia neuropathic pain cinnabarinic acid metabotropic glutamate receptor 4 inflammatory pain |
| url | https://www.frontiersin.org/articles/10.3389/fnmol.2022.892870/full |
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