Dietary fish oil inhibits mechanical allodynia and thermal hyperalgesia in diabetic rats by blocking nuclear factor-κB-mediated inflammatory pathways

Li, Mengying; Wang, Yayun; Cao, Rui; Hou, Xiang-Hong; Zhang, Lei; Yang, Rui; Wang, Feng

doi:10.1016/j.jnutbio.2015.05.005

Cited by 19 publications

(9 citation statements)

References 46 publications

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“…A possible modulation of glial cells, which are considered the main producers of TNF at the spinal cord, may be involved in these effects ( Ignatowski et al, 1999 ; Hanisch, 2002 ). Also, it was previously demonstrated that DHA modulates microglia activation through inhibition of TNF release in cultured cells and FO supplementation was able of decreasing TNF levels in rats DRGs ( Antonietta Ajmone-Cat et al, 2012 ; Li et al, 2015 ). Considering neutrophil role in NP development and maintenance, it has been observed that depletion of these cells at the time of nerve injury attenuate hypersensitivity, however, the same effect is not detected after later depletion ( Perkins and Tracey, 2000 ; Zuo et al, 2003 ).…”

Section: Discussionmentioning

confidence: 95%

Long-Chain Omega-3 Fatty Acids Supplementation Accelerates Nerve Regeneration and Prevents Neuropathic Pain Behavior in Mice

et al. 2017

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Fish oil (FO) is the main source of long chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs), which display relevant analgesic and anti-inflammatory properties. Peripheral nerve injury is driven by degeneration, neuroinflammation, and neuronal plasticity which results in neuropathic pain (NP) symptoms such as allodynia and hyperalgesia. We tested the preventive effect of an EPA/DHA-concentrate fish oil (CFO) on NP development and regenerative features. Swiss mice received daily oral treatment with CFO 4.6 or 2.3 g/kg for 10 days after NP was induced by partial sciatic nerve ligation. Mechanical allodynia and thermal hypernociception were assessed 5 days after injury. CFO 2.3 g/kg significantly prevented mechanical and thermal sensitization, reduced TNF levels in the spinal cord, sciatic MPO activity, and ATF-3 expression on DRG cells. CFO improved Sciatic Functional Index (SFI) as well as electrophysiological recordings, corroborating the increased GAP43 expression and total number of myelinated fibers observed in sciatic nerve. No locomotor activity impairment was observed in CFO treated groups. These results point to the regenerative and possibly protective properties of a combined EPA and DHA oral administration after peripheral nerve injury, as well as its anti-neuroinflammatory activity, evidencing ω-3 PUFAs promising therapeutic outcomes for NP treatment.

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Section: Discussionmentioning

confidence: 95%

Long-Chain Omega-3 Fatty Acids Supplementation Accelerates Nerve Regeneration and Prevents Neuropathic Pain Behavior in Mice

et al. 2017

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“…The current results in diabetic mice support an often observed lack of efficacy of non‐steroidal anti‐inflammatory drugs on neuropathic pain in humans and animal models (Gore et al., ; Wagner et al., ; Mendlik and Uritsky, ). DHA has recently demonstrated effects in diabetic pain models often attributed to its anti‐inflammatory activity (Heng et al., ; Li et al., ). However, if chronic neuropathy were treated by anti‐inflammatory action alone, we would have expected celecoxib to have an antihyperalgesic effect which was not the case, although both the EDPs and the sEHI were efficacious against the neuropathic pain.…”

Section: Resultsmentioning

confidence: 99%

Epoxy fatty acids mediate analgesia in murine diabetic neuropathy

Wagner

Lee

Yang

2016

European Journal of Pain

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Background Neuropathic pain is a debilitating condition with no adequate therapy. The health benefits of omega‐3 fatty acids are established, however, the role of docosahexaenoic acid (DHA) in limiting pain has only recently been described and the mechanisms of this action remain unknown. DHA is metabolized into epoxydocosapentanoic acids (EDPs) via cytochrome P450 (CYP450) enzymes which are substrates for the soluble epoxide hydrolase (sEH) enzyme. Here, we tested several hypotheses; first, that the antinociceptive action of DHA is mediated by the EDPs. Second, based on evidence that DHA and CYP450 metabolites elicit analgesia through opioid signalling, we investigated this as a possible mechanism of action. Third, we tested whether the analgesia mediated by epoxy fatty acids had similar rewarding effects as opioid analgesics. Methods We tested diabetic neuropathic wild‐type and sEH null mice in a conditioned place preference assay for their response to EDPs, sEHI and antagonism of these treatments with naloxone, a mu‐opioid receptor antagonist. Results The EDPs and sEH inhibitors were efficacious against chronic pain, and naloxone antagonized the action of both EDPs and sEH inhibitors. Despite this antagonism, the sEH inhibitors lacked reward side effects differing from opioids. Conclusions The EpFA are analgesic against chronic pain differing from opioids which have limited efficacy in chronic conditions. Significance EDPs and sEHI mediate analgesia in modelled chronic pain and this analgesia is blocked by naloxone. However, unlike opioids, sEHI are highly effective in neuropathic pain models and importantly lack rewarding side effects.

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“…They found that either agent reduced the elevated levels of pro-inflammatory cytokines, inducible nitric oxide synthase and cyclooxygenase-2 (COX-2). Li et al found that treating diabetic rats with fish oil inhibited mechanical allodynia and thermal hyperalgesia by blocking NF-κB and increasing phosphorylation of protein kinase B (AKT) in dorsal root ganglia [ 40 ]. Kellogg et al has also reported that inhibition of COX-2 provides protection against various diabetic peripheral neuropathy deficits [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Fish oil Vs. Resolvin D1, E1, Methyl Esters of Resolvins D1 or D2 on Diabetic Peripheral Neuropathy

Obrosov

Coppey

Shevalye

et al. 2017

J Neurol Neurophysiol

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ObjectiveFish oil is enriched in omega-3 polyunsaturated fatty acids primarily eicosapentaenoic and docosahexaenoic fatty acids. Metabolites of these two polyunsaturated fatty acids include the E and D series resolvins. Omega-3 polyunsaturated fatty acids and resolvins have been reported to have anti-inflammatory and neuroprotective properties. The objective of this study was to evaluate the efficacy of menhaden oil, a fish oil derived from the menhaden, resolvins D1 and E1 and the methyl esters of resolvins D1 and D2 on diabetic peripheral neuropathy. Hypothesis being examined was that the methyl esters of resolvins D1 and D2 would be move efficacious than resolvins D1 or E1 due to an extended half-life.MethodsA model of type 2 diabetes in C57BL/6J mice was created through a combination of a high fat diet followed 8 weeks later with treatment of low dosage of streptozotocin. After 8 weeks of untreated hyperglycemia type 2 diabetic mice were treated for 8 weeks with menhaden oil in the diet or daily injections of 1 ng/g body weight resolvins D1, E1 or methyl esters of resolvins D1 or D2. Afterwards, multiple neurological endpoints were examined.ResultsMenhaden oil or resolvins did not improve hyperglycemia. Untreated diabetic mice were thermal hypoalgesic, had mechanical allodynia, reduced motor and sensory nerve conduction velocities and decreased innervation of the cornea and skin. These endpoints were significantly improved with menhaden oil or resolvin treatment. However, the methyl esters of resolvins D1 or D2, contrary to our hypothesis, were generally less potent than menhaden oil or resolvins D1 or E1.ConclusionThese studies further support omega-3 polyunsaturated fatty acids derived from fish oil via in part due to their metabolites could be an effective treatment for diabetic neuropathy.

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Dietary fish oil inhibits mechanical allodynia and thermal hyperalgesia in diabetic rats by blocking nuclear factor-κB-mediated inflammatory pathways

Cited by 19 publications

References 46 publications

Long-Chain Omega-3 Fatty Acids Supplementation Accelerates Nerve Regeneration and Prevents Neuropathic Pain Behavior in Mice

Long-Chain Omega-3 Fatty Acids Supplementation Accelerates Nerve Regeneration and Prevents Neuropathic Pain Behavior in Mice

Epoxy fatty acids mediate analgesia in murine diabetic neuropathy

Effect of Fish oil Vs. Resolvin D1, E1, Methyl Esters of Resolvins D1 or D2 on Diabetic Peripheral Neuropathy

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