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Volume 13
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10.3390/brainsci13060858
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Article

Phenytoin Decreases Pain-like Behaviors and Improves Opioid Analgesia in a Rat Model of Neuropathic Pain

by
Magdalena Kocot-Kępska
1,*,
Katarzyna Pawlik
2,
Katarzyna Ciapała
2,
Wioletta Makuch
2,
Renata Zajączkowska
3,
Jan Dobrogowski
1,
Anna Przeklasa-Muszyńska
1 and
Joanna Mika
2,*
1
Department of Pain Research and Treatment, Jagiellonian University Medical College, 31-501 Krakow, Poland
2
Department of Pain Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, 31-343 Krakow, Poland
3
Department of Interdisciplinary Intensive Care, Jagiellonian University Medical College, 30-688 Krakow, Poland
*
Authors to whom correspondence should be addressed.
Brain Sci. 2023, 13(6), 858; https://doi.org/10.3390/brainsci13060858
Submission received: 18 April 2023 / Revised: 18 May 2023 / Accepted: 24 May 2023 / Published: 25 May 2023
(This article belongs to the Special Issue Recent Advances in Pain Research)
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Abstract

Neuropathic pain remains a clinical challenge due to its complex and not yet fully understood pathomechanism, which result in limited analgesic effectiveness of the management offered, particularly for patients with acute, refractory neuropathic pain states. In addition to the introduction of several modern therapeutic approaches, such as neuromodulation or novel anti-neuropathic drugs, significant efforts have been made in the repurposing of well-known substances such as phenytoin. Although its main mechanism of action occurs at sodium channels in excitable and non-excitable cells and is well documented, how the drug affects the disturbed neuropathic interactions at the spinal cord level and how it influences morphine-induced analgesia have not been clarified, both being crucial from a clinical perspective. We demonstrated that single and repeated systemic administrations of phenytoin decreased tactile and thermal hypersensitivity in an animal model of neuropathic pain. Importantly, we observed an increase in the antinociceptive effect on thermal stimuli with repeated administrations of phenytoin. This is the first study to report that phenytoin improves morphine-induced antinociceptive effects and influences microglia/macrophage activity at the spinal cord and dorsal root ganglion levels in a neuropathic pain model. Our findings support the hypothesis that phenytoin may represent an effective strategy for neuropathic pain management in clinical practice, particularly when combination with opioids is needed.
Keywords: phenytoin; neuropathic pain; morphine; glia; neuroinflammation phenytoin; neuropathic pain; morphine; glia; neuroinflammation

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MDPI and ACS Style

Kocot-Kępska, M.; Pawlik, K.; Ciapała, K.; Makuch, W.; Zajączkowska, R.; Dobrogowski, J.; Przeklasa-Muszyńska, A.; Mika, J. Phenytoin Decreases Pain-like Behaviors and Improves Opioid Analgesia in a Rat Model of Neuropathic Pain. Brain Sci. 2023, 13, 858. https://doi.org/10.3390/brainsci13060858

AMA Style

Kocot-Kępska M, Pawlik K, Ciapała K, Makuch W, Zajączkowska R, Dobrogowski J, Przeklasa-Muszyńska A, Mika J. Phenytoin Decreases Pain-like Behaviors and Improves Opioid Analgesia in a Rat Model of Neuropathic Pain. Brain Sciences. 2023; 13(6):858. https://doi.org/10.3390/brainsci13060858

Chicago/Turabian Style

Kocot-Kępska, Magdalena, Katarzyna Pawlik, Katarzyna Ciapała, Wioletta Makuch, Renata Zajączkowska, Jan Dobrogowski, Anna Przeklasa-Muszyńska, and Joanna Mika. 2023. "Phenytoin Decreases Pain-like Behaviors and Improves Opioid Analgesia in a Rat Model of Neuropathic Pain" Brain Sciences 13, no. 6: 858. https://doi.org/10.3390/brainsci13060858

APA Style

Kocot-Kępska, M., Pawlik, K., Ciapała, K., Makuch, W., Zajączkowska, R., Dobrogowski, J., Przeklasa-Muszyńska, A., & Mika, J. (2023). Phenytoin Decreases Pain-like Behaviors and Improves Opioid Analgesia in a Rat Model of Neuropathic Pain. Brain Sciences, 13(6), 858. https://doi.org/10.3390/brainsci13060858

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