Analgetic effect of docosahexaenoic acid is mediated by modulating the microglia activity in the dorsal root ganglia in a rat model of neuropathic pain

Manzhulo, Igor; Огурцова, О. С.; Lamash, N. E.; Латышев, Н. А.; Kasyanov, Sergey P.; Dyuizen, I. V.

doi:10.1016/j.acthis.2015.07.001

Cited by 19 publications

(14 citation statements)

References 54 publications

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“…Indeed, previous studies have reported analgesic properties of FO in thermal nociception and in mechanical allodynia associated with diabetic neuropathy ( Redivo et al, 2016 ). DHA alone has also shown anti-nociceptive effect attenuating inflammatory pain, NP, and painful diabetic neuropathy in rodents ( Lu et al, 2013 ; Manzhulo et al, 2015 ). Accordingly, the benefits from ω-3 PUFAs consumption in NP management has been reported in a study in which heterogeneous NP patients achieved significant pain alleviation with FO treatment ( Ko et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

“…DHA is the most abundant PUFA in cell membrane composition and is the main studied ω-3 as modulator of the nervous systems ( Bazan, 2007 ). Regarding to pain, it is described for DHA an antinociceptive effect after thermal and chemical stimuli and also prevention of NP development through the modulation of macrophage and microglia ( Nakamoto et al, 2010 ; Manzhulo et al, 2015 ). Also, the exact mechanisms involved in these effects are inconclusive with reports showing that ω-3 PUFAs could activate GPR120 signaling, modulate TRPV1, and interfere with cytokines gene transcription via NF- κB and PPARγ ( Matta et al, 2007 ; Oh et al, 2010 ; Calder, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

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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: 99%

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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“…In contrast, to respond severe oxidative stress, p53 exhibits prooxidant activities and leads to cell death [41]. Therefore, it is not difficult to interpret the controversial data that n-3 PUFA may inhibit [42, 43] or induce [44, 45] p53 expression in both in vivo and in vitro experiments. However, none of these studies have addressed the effects of n-3 PUFA on p53 expression in an anti-aging view.…”

Section: Discussionmentioning

confidence: 99%

Polyunsaturated fatty acids ameliorate aging via redox-telomere-antioncogene axis

et al. 2016

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Polyunsaturated fatty acids (PUFA), a group of nourishing and health-promoting nutrients, ameliorate age-related chronic diseases. However, how PUFA especially n-3 PUFA exert anti-aging functions remains poorly understood. Here we link fish oil, docosahexaenoic acid (DHA) and arachidonic acid (AA) to the aging etiology via a redox-telomere-antioncogene axis based on D-galactose-induced aging mice. Both fish oil and PUFA enhanced hepatic superoxide dismutase (SOD) and catalase activities and cardiac SOD activities within the range of 18%-46%, 26%-65% and 19%-58%, respectively, whereas reduced cerebral monoamine oxidase activity, plasma F2-isoprostane level and cerebral lipid peroxidation level by 56%-90%, 20%-79% and 16%-54%, respectively. Thus, PUFA improve the in vivo redox and oxidative stress induced aging process, which however does not exhibit a dose-dependent manner. Notably, both PUFA and fish oil effectively inactivated testicular telomerase and inhibited c-Myc-mediated telomerase reverse transcriptase expression, whereas n-3 PUFA rather than n-6 PUFA protected liver and testes against telomere shortening within the range of 13%-25% and 25%-27%, respectively. Therefore, n-3 PUFA may be better at inhibiting the DNA damage induced aging process. Surprisingly, only DHA significantly suppressed cellular senescence pathway evidenced by testicular antioncogene p16 and p53 expression. This work provides evident support for the crosstalk between PUFA especially n-3 PUFA and the aging process via maintaining the in vivo redox homeostasis, rescuing age-related telomere attrition and down-regulating the antioncogene expression.

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“…Many studies have reported a close relationship between microglial function and n-3 PUFAs since then. N-3 PUFA supplementation reduces microglial activation and/or phenotype alteration in models of brain development (Kuperstein et al, 2008;Madore et al, 2014;Abiega et al, 2016), respiratory system development (Tenorio-Lopes et al, 2017), healthy aging (Grundy et al, 2014), ischemia (Zhang et al, 2010;Belayev et al, 2011;Okabe et al, 2011;Eady et al, 2012aEady et al, ,b, 2014Chang et al, 2013;Zendedel et al, 2015;Jiang et al, 2016), spinal cord injury (Huang et al, 2007;Lim et al, 2013a,b;Paterniti et al, 2014;Tremoleda et al, 2016;Xu et al, 2016), Parkinson's disease (Muntane et al, 2010;Ji et al, 2012;Tian et al, 2015;Delattre et al, 2017;Mori et al, 2017), AD (Lynch et al, 2007;Hopperton et al, 2016;Serini and Calviello, 2016;Wen et al, 2016), systemic inflammation (Delpech et al, 2015b), traumatic brain injury (Pu et al, 2013;Harrison et al, 2015;Harvey et al, 2015;Desai et al, 2016), neuropathic pain model (Xu et al, 2013b;Manzhulo et al, 2015;Huang and Tsai, 2016), aging (Labrousse et al, 2012), demyelination (Chen et al, 2014), amyotrophic lateral sclerosis…”

Section: Microglia As a Target For N-3 Pufas And Spmsmentioning

confidence: 99%

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

Layé¹,

Nadjar²,

Joffre³

et al. 2017

Pharmacol Rev

324

190

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Classically, polyunsaturated fatty acids (PUFA) were largely thought to be relatively inert structural components of brain, largely important for the formation of cellular membranes. Over the past 10 years, a host of bioactive lipid mediators that are enzymatically derived from arachidonic acid, the main n-6 PUFA, and docosahexaenoic acid, the main n-3 PUFA in the brain, known to regulate peripheral immune function, have been detected in the brain and shown to regulate microglia activation. Recent advances have focused on how PUFA regulate the molecular signaling of microglia, especially in the context of neuroinflammation and behavior. Several active drugs regulate brain lipid signaling and provide proof of concept for targeting the brain. Because brain lipid metabolism relies on a complex integration of diet, peripheral metabolism, including the liver and blood, which supply the brain with PUFAs that can be altered by genetics, sex, and aging, there are many pathways that can be disrupted, leading to altered brain lipid homeostasis. Brain lipid signaling pathways are altered in neurologic disorders and may be viable targets for the development of novel therapeutics. In this study, we discuss in particular how n-3 PUFAs and their metabolites regulate microglia phenotype and function to exert their anti-inflammatory and proresolving activities in the brain.

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Analgetic effect of docosahexaenoic acid is mediated by modulating the microglia activity in the dorsal root ganglia in a rat model of neuropathic pain

Cited by 19 publications

References 54 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

Polyunsaturated fatty acids ameliorate aging via redox-telomere-antioncogene axis

Anti-Inflammatory Effects of Omega-3 Fatty Acids in the Brain: Physiological Mechanisms and Relevance to Pharmacology

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