Analgesia enhancement and prevention of tolerance to morphine: beneficial effects of combined therapy with omega-3 fatty acids

Escudero, Graciela; Romañuk, Carolina Beatriz; Toledo, María Eugenia; Olivera, Marı́a Eugenia; Manzo, Rubén H.; Laino, Carlos Horacio

doi:10.1111/jphp.12416

Cited by 25 publications

(22 citation statements)

References 57 publications

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“…cally quantified and analyzed statistically. However, there is evidence in the literature, that omega-3 fatty acids may indeed influence pain sensation by an antinociceptive property (12,13). This interesting feature should therefore be in the focus of further investigations.…”

Section: Discussionmentioning

confidence: 92%

Marine Omega3 wound matrix for the treatment of complicated wounds

Trinh¹,

Dünschede²,

Vahl³

et al. 2016

Phlebologie

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Summary Introduction Complicated wounds in the lower extremity can arise as a consequence of insufficient soft-tissue coverage after amputations in diabetic patients. The Kerecis® Omega3 wound matrix is a decellularized skin matrix derived from codfish and represents an alternative treatment option to achieve wound healing. Methods 5 patients with diabetes mellitus and complicated wounds in the lower limb with exposed bony segments were treated with the Omega3 wound matrix between November 2014 and November 2015. Following initial debridement in the operating room, the wound matrix was applied and covered with a silicone mesh. In the further course, wound treatment was conducted on outpatient setting. Results In total, 7 wounds were treated with localization at the level of the thigh (n=2) and the forefoot (n=5). For the wounds at the thigh, it took 26 weeks to achieve wound closure, whereas the wounds at the level of the forefoot showed healing times between 13 and 41 weeks. In all patients, a reduction of analgetics intake was noted when the treatment with the Omega3 wound matrix was initiated. Conclusion The Kerecis® Omega3 wound matrix represents a viable treatment option in complicated wounds in the lower limb of diabetic patients to circumvent an otherwise necessary proximalization of amputation level. Further studies comparing the Omega3 wound matrix with appropriate control groups of standard therapies for soft-tissue conditioning/coverage like negative pressure therapy, biosurgery and other acellular dermal matrices are warranted.

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Section: Discussionmentioning

confidence: 92%

Marine Omega3 wound matrix for the treatment of complicated wounds

Trinh¹,

Dünschede²,

Vahl³

et al. 2016

Phlebologie

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“…We recently demonstrated that naloxone, a pure opioid antagonist, blocks the analgesia produced by omega-3 PUFAs alone or in co-administration of omega-3 PUFAs with morphine, suggesting that the analgesic activity of both might be exerted via a mechanism related to the opioid system [104].…”

Section: Omega-3 Fatty Acids Combined With Morphinementioning

confidence: 99%

“…Moreover, morphine reduces the gastrointestinal transit, whereas co-administration of omega-3 PUFAs with morphine blocks this morphine effect [104].…”

Section: Omega-3 Fatty Acids Combined With Morphinementioning

confidence: 99%

“…Furthermore, a new pharmaceutical mixture (omega-3 PUFA/morphine) obtained by dissolving morphine in salmon oil allowed the concomitant oral administration of both components, which showed analgesic activity with a subtherapeutic dose of morphine, lower side-effects associated with morphine treatment, and also prevented or least reduced the possibility of developing tolerance to the analgesic effect of morphine [104,105] The exact mechanism by which omega-3 PUFAs reduce pain is not fully understood, but some reports about the mechanisms underlying the antinociceptive effect of omega-3 PUFAs have suggested that this pain reduction occurs through:…”

Section: Omega-3 Fatty Acids Combined With Morphinementioning

confidence: 99%

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Innovations in Pain Management: Morphine Combined with Omega-3 Fatty Acids

Laino¹

2017

Open Conf. Proceed. J.

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Abstract:The treatment of acute and chronic severe pain remains a common major challenge faced by clinicians working with the general population, and even after the application of recent advances to treatments, there may still continue to be manifestations of adverse effects.Chronic pain affects the personal and social life of the patient, and often also their families. In some cases, after an acute pain the patient continues to experience chronic pain, which can be a result of diseases such as cancer.Morphine is recommended as the first choice opioid in the treatment of moderate to severe acute and chronic pain. However, the development of adverse effects and tolerance to the analgesic effects of morphine often leads to treatment discontinuation. The present work reviews the different pharmaceutical innovations reported concerning the use of morphine. First, its utilization as the first medication for the treatment of moderate to severe cancer pain and non-cancer pain in patients is evaluated, taking into account the most common complications and adverse effects. Next, strategies utilized to manage these side effects are considered, and we also summarize results using omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) as a monotherapy or as an adjunct to morphine in the treatment of pain.

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“…Tolerance is one of significant side-effects in morphine-induced antinociception 1 2 . Some proteins can be regulated in tolerance.…”

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confidence: 99%

siRNA capsulated brain-targeted nanoparticles specifically knock down OATP2B1 in mice: a mechanism for acute morphine tolerance suppression

Yang

Wang

et al. 2016

Sci Rep

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Regulating main brain-uptake transporter of morphine may restrict its tolerance generation, then modify its antinociception. In this study, more than 2 fold higher intracellular uptake concentrations for morphine and morphine-6-glucuronide (M6G) were observed in stable expression cells, HEK293-hOATP2B1 than HEK293-MOCK. Specifically, the Km value of morphine to OATP2B1 (57.58 ± 8.90 μM) is 1.4-time more than that of M6G (80.31 ± 21.75 μM); Cyclosporine A (CsA), an inhibitor of OATP2B1, can inhibit their intracellular accumulations with IC50 = 3.90 ± 0.50 μM for morphine and IC50 = 6.04 ± 0.86 μM for M6G, respectively. To further investigate the role of OATP2B1 in morphine brain transport and tolerance, the novel nanoparticles of DGL-PEG/dermorphin capsulated siRNA (OATP2B1) were applied to deliver siRNA into mouse brain. Along with OATP2B1 depressed, a main reduction was found for each of morphine or M6G in cerebrums or epencephalons of acute morphine tolerance mice. Furthermore, calcium/calmodulin-dependent protein kinase IIα (CaMKIIα) in mouse prefrontal cortex (mPFC) underwent dephosphorylation at Thr286. In conclusion, OATP2B1 downregulation in mouse brain can suppress tolerance via blocking morphine and M6G brain transport. These findings might help to improve the pharmacological effects of morphine.

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Analgesia enhancement and prevention of tolerance to morphine: beneficial effects of combined therapy with omega-3 fatty acids

Abstract: This finding suggests a role for O3 as adjuncts to opioids in pain therapy and might contribute to the reduction of the occurrence of morphine side-effects.

Cited by 25 publications

References 57 publications

Marine Omega3 wound matrix for the treatment of complicated wounds

Marine Omega3 wound matrix for the treatment of complicated wounds

Innovations in Pain Management: Morphine Combined with Omega-3 Fatty Acids

siRNA capsulated brain-targeted nanoparticles specifically knock down OATP2B1 in mice: a mechanism for acute morphine tolerance suppression

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