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

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-1ß and TNF-α). 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.

Coadministración de oxicodona y metadona para reducir la neurotoxicidad opioide y proveer analgesia: presentación de un caso / Co-administration of oxycodone and metadone to reduce central nervous system side-effects and provide analgesia: case report

Este artículo describe la coadministración de dos opioides agonistas en un paciente que padece dolor de origen oncológico, con la intención de disminuir la toxicidad opioide sobre el Sistema Nervioso Central y mantener un adecuado nivel de analgesia. La oxicodona y la metadona, usualmente utilizadas en humanos, son eficaces analgésicos alternativos de la morfina para tratar dolor moderado a severo. Está bien establecido que la oxicodona actúa sobre los receptores Mu y recientemente se determinó su acción sobre los receptores Kappa. La metadona, por el contrario, es agonista Mu y antagonista competitivo del receptor N-Metil-Di-Aspartato (NMDA). Cuando se los administra conjuntamente, se amplia el espectro de acción sobre diferentes receptores; esto permite disminuir la dosis de cada uno de ellos y contribuir así a revertir la neurotoxicidad opioide que presentaba el paciente. Sin embargo, es necesario realizar trabajos de investigación clínica controlados que avalen esta presunción teórica. (AU)