Effects of dextromethorphan and oxycodone on treatment of neuropathic pain in mice

Pao Pao Yang, Geng Chang Yeh, Eagle Yi Kung Huang, Ping Yee Law, Horace H. Loh, Pao Luh Tao

研究成果: 雜誌貢獻文章

10 引文 (Scopus)

摘要

Background: Neuropathic pain is a very troublesome and difficult pain to treat. Although opioids are the best analgesics for cancer and surgical pain in clinic, only oxycodone among opioids shows better efficacy to alleviate neuropathic pain. However, many side effects associated with the use of oxycodone render the continued use of it in neuropathic pain treatment undesirable. Hence, we explored whether dextromethorphan (DM, a known N-methyl-D-aspartate receptor antagonist with neuroprotective properties) could potentiate the anti-allodynic effect of oxycodone and underlying mechanisms regarding to glial cells (astrocytes and microglia) activation and proinflammatory cytokines release in a spinal nerve injury (SNL) mice model. Results: Oxycodone produced a dose-dependent anti-allodynic effect. Co-administration of DM at a dose of 10 mg/kg (i.p.) (DM10) which had no anti-allodynic effect by itself enhanced the acute oxycodone (1 mg/kg, s.c.) effect. When the chronic anti-allodynic effects were examined, co-administration of DM10 also significantly enhanced the oxycodone effect at 3 mg/kg. Furthermore, oxycodone decreased SNL-induced activation of glial cells (astrocytes and microglia) and plasma levels of proinflammatory cytokines (IL-6, IL-1β and TNF-aα). Co-administration of DM10 potentiated these effects of oxycodone. Conclusion: The combined use of DM with oxycodone may have therapeutic potential for decreasing the effective dose of oxycodone on the treatment of neuropathic pain. Attenuation of the glial activation and proinflammatory cytokines in the spinal cord may be important mechanisms for these effects of DM.

原文英語
期刊Journal of Biomedical Science
DOIs
出版狀態接受/付印 - 九月 22 2015

指紋

Oxycodone
Dextromethorphan
Neuralgia
Neuroglia
Therapeutics
Chemical activation
Microglia
Cytokines
Astrocytes
Opioid Analgesics
Pain Clinics
Spinal Injuries
Spinal Nerves
N-Methyl-D-Aspartate Receptors
Interleukin-1
Analgesics
Interleukin-6
Spinal Cord

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Molecular Biology
  • Cell Biology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism
  • Pharmacology (medical)

引用此文

Yang, P. P., Yeh, G. C., Huang, E. Y. K., Law, P. Y., Loh, H. H., & Tao, P. L. (認可的出版社/出版中). Effects of dextromethorphan and oxycodone on treatment of neuropathic pain in mice. Journal of Biomedical Science. https://doi.org/10.1186/s12929-015-0186-3

Effects of dextromethorphan and oxycodone on treatment of neuropathic pain in mice. / Yang, Pao Pao; Yeh, Geng Chang; Huang, Eagle Yi Kung; Law, Ping Yee; Loh, Horace H.; Tao, Pao Luh.

於: Journal of Biomedical Science, 22.09.2015.

研究成果: 雜誌貢獻文章

Yang, Pao Pao ; Yeh, Geng Chang ; Huang, Eagle Yi Kung ; Law, Ping Yee ; Loh, Horace H. ; Tao, Pao Luh. / Effects of dextromethorphan and oxycodone on treatment of neuropathic pain in mice. 於: Journal of Biomedical Science. 2015.
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abstract = "Background: Neuropathic pain is a very troublesome and difficult pain to treat. Although opioids are the best analgesics for cancer and surgical pain in clinic, only oxycodone among opioids shows better efficacy to alleviate neuropathic pain. However, many side effects associated with the use of oxycodone render the continued use of it in neuropathic pain treatment undesirable. Hence, we explored whether dextromethorphan (DM, a known N-methyl-D-aspartate receptor antagonist with neuroprotective properties) could potentiate the anti-allodynic effect of oxycodone and underlying mechanisms regarding to glial cells (astrocytes and microglia) activation and proinflammatory cytokines release in a spinal nerve injury (SNL) mice model. Results: Oxycodone produced a dose-dependent anti-allodynic effect. Co-administration of DM at a dose of 10 mg/kg (i.p.) (DM10) which had no anti-allodynic effect by itself enhanced the acute oxycodone (1 mg/kg, s.c.) effect. When the chronic anti-allodynic effects were examined, co-administration of DM10 also significantly enhanced the oxycodone effect at 3 mg/kg. Furthermore, oxycodone decreased SNL-induced activation of glial cells (astrocytes and microglia) and plasma levels of proinflammatory cytokines (IL-6, IL-1β and TNF-aα). Co-administration of DM10 potentiated these effects of oxycodone. Conclusion: The combined use of DM with oxycodone may have therapeutic potential for decreasing the effective dose of oxycodone on the treatment of neuropathic pain. Attenuation of the glial activation and proinflammatory cytokines in the spinal cord may be important mechanisms for these effects of DM.",
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T1 - Effects of dextromethorphan and oxycodone on treatment of neuropathic pain in mice

AU - Yang, Pao Pao

AU - Yeh, Geng Chang

AU - Huang, Eagle Yi Kung

AU - Law, Ping Yee

AU - Loh, Horace H.

AU - Tao, Pao Luh

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N2 - Background: Neuropathic pain is a very troublesome and difficult pain to treat. Although opioids are the best analgesics for cancer and surgical pain in clinic, only oxycodone among opioids shows better efficacy to alleviate neuropathic pain. However, many side effects associated with the use of oxycodone render the continued use of it in neuropathic pain treatment undesirable. Hence, we explored whether dextromethorphan (DM, a known N-methyl-D-aspartate receptor antagonist with neuroprotective properties) could potentiate the anti-allodynic effect of oxycodone and underlying mechanisms regarding to glial cells (astrocytes and microglia) activation and proinflammatory cytokines release in a spinal nerve injury (SNL) mice model. Results: Oxycodone produced a dose-dependent anti-allodynic effect. Co-administration of DM at a dose of 10 mg/kg (i.p.) (DM10) which had no anti-allodynic effect by itself enhanced the acute oxycodone (1 mg/kg, s.c.) effect. When the chronic anti-allodynic effects were examined, co-administration of DM10 also significantly enhanced the oxycodone effect at 3 mg/kg. Furthermore, oxycodone decreased SNL-induced activation of glial cells (astrocytes and microglia) and plasma levels of proinflammatory cytokines (IL-6, IL-1β and TNF-aα). Co-administration of DM10 potentiated these effects of oxycodone. Conclusion: The combined use of DM with oxycodone may have therapeutic potential for decreasing the effective dose of oxycodone on the treatment of neuropathic pain. Attenuation of the glial activation and proinflammatory cytokines in the spinal cord may be important mechanisms for these effects of DM.

AB - Background: Neuropathic pain is a very troublesome and difficult pain to treat. Although opioids are the best analgesics for cancer and surgical pain in clinic, only oxycodone among opioids shows better efficacy to alleviate neuropathic pain. However, many side effects associated with the use of oxycodone render the continued use of it in neuropathic pain treatment undesirable. Hence, we explored whether dextromethorphan (DM, a known N-methyl-D-aspartate receptor antagonist with neuroprotective properties) could potentiate the anti-allodynic effect of oxycodone and underlying mechanisms regarding to glial cells (astrocytes and microglia) activation and proinflammatory cytokines release in a spinal nerve injury (SNL) mice model. Results: Oxycodone produced a dose-dependent anti-allodynic effect. Co-administration of DM at a dose of 10 mg/kg (i.p.) (DM10) which had no anti-allodynic effect by itself enhanced the acute oxycodone (1 mg/kg, s.c.) effect. When the chronic anti-allodynic effects were examined, co-administration of DM10 also significantly enhanced the oxycodone effect at 3 mg/kg. Furthermore, oxycodone decreased SNL-induced activation of glial cells (astrocytes and microglia) and plasma levels of proinflammatory cytokines (IL-6, IL-1β and TNF-aα). Co-administration of DM10 potentiated these effects of oxycodone. Conclusion: The combined use of DM with oxycodone may have therapeutic potential for decreasing the effective dose of oxycodone on the treatment of neuropathic pain. Attenuation of the glial activation and proinflammatory cytokines in the spinal cord may be important mechanisms for these effects of DM.

KW - Allodynia

KW - Dextromethorphan

KW - Neuropathic pain

KW - Oxycodone

KW - Spinal nerve ligation

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