Dextromethorphan Attenuated Inflammation and Combined Opioid Use in Humans Undergoing Methadone Maintenance Treatment

Lee, Sheng Yu; Tao, Pao‐Luh; Chang, Yun Hsuan; Chen, Shih‐Heng; Chu, Chun Hsien; Chen, Po See; Lee, I. Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Hong, Jau–Shyong; Lu, Ru Band

doi:10.1007/s11481-012-9400-1

Cited by 23 publications

(22 citation statements)

References 49 publications

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“…The elevated systemic inflammation in IDUs that we observed is consistent with previous studies [ 16 , 17 , 87 – 89 ], and may contribute to co-morbidities within this population. Chronic inflammation is associated with cardiovascular disease, kidney disease, accelerated aging, and neurodegenerative diseases, all of which are increased among IDUs [ 4 , 74 – 79 ].…”

Section: Discussionsupporting

confidence: 92%

“…Several studies have reported elevated inflammatory mediators associated with IDUs, including serum IL-1β, IL-6, and IL-8 in methadone-maintained IDUs [ 16 ] [ 17 ], and increased dendritic cell and natural killer cell activation in IDUs that is associated with needle sharing [ 18 ]. These findings suggest that multiple mediators may be contributing to altered immune homeostasis in IDUs.…”

Section: Introductionmentioning

confidence: 99%

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Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users

et al. 2016

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BackgroundInjection drug use is a growing major public health concern. Injection drug users (IDUs) have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles.Methods and FindingsA comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19) and healthy control subjects (n = 19). The IDU group had substantial polydrug use, with 89% reporting cocaine injection within the preceding month. IDUs exhibited a significant, 2-fold increase in total B cells compared to healthy subjects, which was associated with increased activated B cell subsets. Although plasma total IgG titers were similar between groups, IDUs had significantly higher IgG3 and IgG4, suggestive of chronic B cell activation. Total IgM was also increased in IDUs, as well as HIV Envelope-specific IgM, suggestive of increased HIV exposure. IDUs exhibited numerous features suggestive of systemic inflammation, including significantly increased plasma sCD40L, TNF-α, TGF-α, IL-8, and ceramide metabolites. Machine learning multivariate analysis distilled a set of 10 features that classified samples based on group with absolute accuracy.ConclusionsThese results demonstrate broad alterations in the steady-state humoral profile of IDUs that are associated with increased systemic inflammation. Such dysregulation may impact the ability of IDUs to generate optimal responses to vaccination and infection, or lead to increased risk for inflammation-related co-morbidities, and should be considered when developing immune-based interventions for this growing population.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users

et al. 2016

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“…inhibits inflammatory mediators, including cytokines (TNF-α, IL-1β and IL-6) and chemokines in sepsis mice model [ 53 ]. Furthermore, our recent clinical study showed that DM (60–120 mg/day, oral) attenuated plasma cytokine TNF-α, which has been increased in methadone-treated heroin addicts [ 54 ]. Our present study demonstrates that SNL induced high plasma levels of IL-6, IL-1β, and TNF-α, and chronic oxycodone (1 mg/kg, s.c.) suppressed all of them significantly (Fig.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2015

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BackgroundNeuropathic 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.ResultsOxycodone 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-α). Co-administration of DM10 potentiated these effects of oxycodone.ConclusionThe 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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“…Dextromethorphan antagonizes the spinal NMDA receptor system, and may manipulate opioid effects via this mechanism [186,187]. Several studies have shown mixed results with dextromethorphan as an adjuvant medication in treating opioid tolerance [188][189][190][191] and withdrawal symptoms [192][193][194][195][196][197]. Numerous studies have cited dextromethorphan's ability to reduce intra-and post-operative morphine consumption [198][199][200], while others have not replicated these findings [201,202].…”

Section: Dextromethorphanmentioning

confidence: 99%

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

et al. 2015

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Opioid analgesics have become a cornerstone in the treatment of moderate to severe pain, resulting in a steady rise of opioid prescriptions. Subsequently, there has been a striking increase in the number of opioid-dependent individuals, opioid-related overdoses, and fatalities. Clinical use of opioids is further complicated by an increasingly deleterious profile of side effects beyond addiction, including tolerance and opioid-induced hyperalgesia (OIH), where OIH is defined as an increased sensitivity to already painful stimuli. This paradoxical state of increased nociception results from acute and long-term exposure to opioids, and appears to develop in a substantial subset of patients using opioids. Recently, there has been considerable interest in developing an efficacious treatment regimen for acute and chronic pain. However, there are currently no well-established treatments for OIH. Several substrates have emerged as potential modulators of OIH, including the N-methyl-D-aspartate and γ-aminobutyric acid receptors, and most notably, the innate neuroimmune system. This review summarizes the neurobiology of OIH in the context of clinical treatment; specifically, we review evidence for several pathways that show promise for the treatment of pain going forward, as prospective adjuvants to opioid analgesics. Overall, we suggest that this paradoxical state be considered an additional target of clinical treatment for chronic pain.

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Dextromethorphan Attenuated Inflammation and Combined Opioid Use in Humans Undergoing Methadone Maintenance Treatment

Cited by 23 publications

References 49 publications

Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users

Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users

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

Targeting Opioid-Induced Hyperalgesia in Clinical Treatment: Neurobiological Considerations

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