NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats
Pannexin 1 (Panx1) is involved in the spinal central sensitization process in rats with neuropathic pain, but its interaction with well-known, pain-related, ligand-dependent receptors, such as NMDA receptors (NMDAR) and P2X7 purinoceptors (P2X7R), remains largely unexplored. Here, we studied whether...
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MDPI AG
2022-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/12/6705 |
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| author | David Bravo Katherine Zepeda-Morales Carola J. Maturana Jeffri S. Retamal Alejandro Hernández Teresa Pelissier Rafael Barra Patricio Sáez-Briones Héctor Burgos Luis Constandil |
| author_facet | David Bravo Katherine Zepeda-Morales Carola J. Maturana Jeffri S. Retamal Alejandro Hernández Teresa Pelissier Rafael Barra Patricio Sáez-Briones Héctor Burgos Luis Constandil |
| author_sort | David Bravo |
| collection | DOAJ |
| description | Pannexin 1 (Panx1) is involved in the spinal central sensitization process in rats with neuropathic pain, but its interaction with well-known, pain-related, ligand-dependent receptors, such as NMDA receptors (NMDAR) and P2X7 purinoceptors (P2X7R), remains largely unexplored. Here, we studied whether NMDAR- and P2X7R-dependent nociceptive signaling in neuropathic rats require the activation of Panx1 channels to generate spinal central sensitization, as assessed by behavioral (mechanical hyperalgesia) and electrophysiological (C-reflex wind-up potentiation) indexes. Administration of either a selective NMDAR agonist i.t. (NMDA, 2 mM) or a P2X7R agonist (BzATP, 150 μM) significantly increased both the mechanical hyperalgesia and the C-reflex wind-up potentiation, effects that were rapidly reversed (minutes) by i.t. administration of a selective pannexin 1 antagonist (10panx peptide, 300 μM), with the scores even reaching values of rats without neuropathy. Accordingly, 300 μM 10panx completely prevented the effects of NMDA and BzATP administered 1 h later, on mechanical hyperalgesia and C-reflex wind-up potentiation. Confocal immunofluorescence imaging revealed coexpression of Panx1 with NeuN protein in intrinsic dorsal horn neurons of neuropathic rats. The results indicate that both NMDAR- and P2X7R-mediated increases in mechanical hyperalgesia and C-reflex wind-up potentiation require neuronal Panx1 channel activation to initiate and maintain nociceptive signaling in neuropathic rats. |
| first_indexed | 2024-03-09T23:33:28Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:33:28Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-bbb8be88c0b74bb1b3018f325931cf792023-11-23T17:05:25ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012312670510.3390/ijms23126705NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic RatsDavid Bravo0Katherine Zepeda-Morales1Carola J. Maturana2Jeffri S. Retamal3Alejandro Hernández4Teresa Pelissier5Rafael Barra6Patricio Sáez-Briones7Héctor Burgos8Luis Constandil9Laboratorio de Neurobiología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, ChileLaboratorio de Neurobiología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, ChilePrinceton Neuroscience Institute, Princeton University, Princeton, NJ 08544, USALaboratorio de Neurobiología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, ChileLaboratorio de Neurobiología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, ChileLaboratorio de Neurobiología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, ChileCentro de Investigación Biomédica y Aplicada (CIBAP), Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Santiago 9170022, ChileLaboratorio de Neurofarmacología y Comportamiento, Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Santiago 9170022, ChileEscuela de Psicología, Facultad de Medicina y Ciencias de la Salud, Universidad Mayor, Santiago 7570008, ChileLaboratorio de Neurobiología, Facultad de Química y Biología, Universidad de Santiago de Chile, Santiago 9170022, ChilePannexin 1 (Panx1) is involved in the spinal central sensitization process in rats with neuropathic pain, but its interaction with well-known, pain-related, ligand-dependent receptors, such as NMDA receptors (NMDAR) and P2X7 purinoceptors (P2X7R), remains largely unexplored. Here, we studied whether NMDAR- and P2X7R-dependent nociceptive signaling in neuropathic rats require the activation of Panx1 channels to generate spinal central sensitization, as assessed by behavioral (mechanical hyperalgesia) and electrophysiological (C-reflex wind-up potentiation) indexes. Administration of either a selective NMDAR agonist i.t. (NMDA, 2 mM) or a P2X7R agonist (BzATP, 150 μM) significantly increased both the mechanical hyperalgesia and the C-reflex wind-up potentiation, effects that were rapidly reversed (minutes) by i.t. administration of a selective pannexin 1 antagonist (10panx peptide, 300 μM), with the scores even reaching values of rats without neuropathy. Accordingly, 300 μM 10panx completely prevented the effects of NMDA and BzATP administered 1 h later, on mechanical hyperalgesia and C-reflex wind-up potentiation. Confocal immunofluorescence imaging revealed coexpression of Panx1 with NeuN protein in intrinsic dorsal horn neurons of neuropathic rats. The results indicate that both NMDAR- and P2X7R-mediated increases in mechanical hyperalgesia and C-reflex wind-up potentiation require neuronal Panx1 channel activation to initiate and maintain nociceptive signaling in neuropathic rats.https://www.mdpi.com/1422-0067/23/12/6705pannexin 1NMDA receptorP2X7 receptorneuropathic painwind-up |
| spellingShingle | David Bravo Katherine Zepeda-Morales Carola J. Maturana Jeffri S. Retamal Alejandro Hernández Teresa Pelissier Rafael Barra Patricio Sáez-Briones Héctor Burgos Luis Constandil NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats International Journal of Molecular Sciences pannexin 1 NMDA receptor P2X7 receptor neuropathic pain wind-up |
| title | NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats |
| title_full | NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats |
| title_fullStr | NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats |
| title_full_unstemmed | NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats |
| title_short | NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats |
| title_sort | nmda and p2x7 receptors require pannexin 1 activation to initiate and maintain nociceptive signaling in the spinal cord of neuropathic rats |
| topic | pannexin 1 NMDA receptor P2X7 receptor neuropathic pain wind-up |
| url | https://www.mdpi.com/1422-0067/23/12/6705 |
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