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. 2023 Oct 18;13:17805. doi: 10.1038/s41598-023-44857-2

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Repeated administration of morphine induces neuronal hyperexcitability and is attenuated by NaBut. (a–c) Representative neuronal action potential traces from isolated DRG neurons from Saline, morphine, and morphine + NaBut treated animals. The left panel shows the actional potential trace taken at 3× rheobase stimulation in a 500 ms pulse protocol, the right panel shows the associated phase plane analysis which is derived from the 1st derivative of the trace on the left, plotted against membrane potential. Repeated administration of morphine increased regenerative action potentials in the 500 ms pulse relative to saline indicating an enhanced neuronal excitability phenotype. This enhanced excitability is attenuated in the NaBut treatment group. Phase plane analysis of the action potential traces reveal a significant loss in maximum rate of membrane potential change during the rising phase of the action potential in the morphine group relative to saline controls, this change in maximum dV/dT is attenuated in the repeated dose morphine + NaBut group implicating voltage gated sodium channels in the potentiation of regenerative action potentials. Floating numbers (1, 2) indicate which action potential corresponds to which portion of the phase plane plots (which overlay one another), it should be noted that maximum rate of change (max dV/dT) occurs during the rising phase of the AP, and before the AP peak.