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

Abstract

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.

Beneficial effects of fish oil enriched in omega-3 fatty acids on the development and maintenance of neuropathic pain

“…Peripheral nerve injury is followed by a cascade of pathophysiological events, including the disorganization of the blood–nerve barrier, the recruitment of circulating macrophages, proliferation of Schwann cells, raised cytokine production, the rearrangement of endoneurial place and production of extra cellular components . Moreover, axonal count after 2 weeks of sciatic nerve injury has been found to increase in mice treated with concentrate fish oil containing EPA and DHA, which supports our finding in the regeneration index at 21 days after CCI.…”

“…Finally, our study supports evidence that fish oil enriched in omega‐3 fatty acids administration produce earlier improvement of pain‐related behaviours than motor functional recovery. As mentioned before, Silva et al . found that omega‐3 administration prevents mechanical allodynia and thermal hyperalgesia in the first 5 days after nerve injury.…”

“…Recent work by Silva et al . in mice studied the effects of EPA/DHA‐concentrate fish oil on neuropathic pain development after partial sciatic nerve ligation (PSNL).…”

“…A reasonable explanation for the time difference between the reestablishment of sensory and motor function after nerve injury is that nerve regeneration is a longer process due to it requires a series of molecular pathways and key genes to express in order to remodel myelin and other nervous structures. Considering that nerve function is strongly linked to myelin integrity, later improvement of SFI in animals treated with omega‐3 components may correspond to the time to express regeneration markers such as GAP‐43 which has been reported to increment 14 days after nerve ligation, while pro‐inflammatory cytokines and immune cell modulation, that are key components of the peripheral and central sensitization mechanisms, have been found to be significantly reduced in the first days after lesion in spinal cord, DRG and nerve tissue …”

Gender-Specific Beneficial Effects of Docosahexaenoic Acid Dietary Supplementation in G93A-SOD1 Amyotrophic Lateral Sclerosis Mice

“…However, the contribution of DHA depletion to the disease remains largely uncharacterized. Alternatively, previous work on DHA metabolism and neurodegeneration demonstrates a positive role of this lipid in Parkinson's disease [13], neuroinflammation [14], cognitive impairment [15], Alzheimer's disease [16], and neuropathic pain [17]. Previously, we showed that a general change in polyunsaturated fatty acid content in diets could influence disease evolution in the B6SJL-Tg (SOD1-G93A)1Gur/J transgenic mice [18].…”