Pro-resolving mediator maresin 1 ameliorates pain hypersensitivity in a rat spinal nerve ligation model of neuropathic pain

Abstract

BackgroundPro-resolving mediators (PRMs) are considered as emerging analgesics for chronic pain. Maresin 1 (MaR1) is a newly identified member of PRMs, and recent studies implicate its potential role in some pain conditions. As the function of MaR1 in neuropathic pain remains unclear, we investigated the effects of MaR1 on pain hypersensitivity and the underlying mechanism using a rat spinal nerve ligation (SNL) model of neuropathic pain.Materials and methodsMaR1 (100 ng/10 μL) or commensurable artificial cerebrospinal fluid was delivered via intrathecal catheter from days 3 to 5 post-SNL followed by assessment of mechanical allodynia and thermal hyperalgesia. Ipsilateral L4–L5 spinal cord tissue was collected on day 7 post-SNL and assessed by Western blotting, enzyme-linked immunosorbent assay or immunohistochemistry.ResultsIntrathecal MaR1 significantly attenuated mechanical allodynia and thermal hyperalgesia from day 5 to day 7 post-SNL, which was associated with decreased spinal levels of glial markers, GFAP and IBA1. It was also found that intrathecal MaR1 downregulated phosphorylation levels of NF-κB p65 and its nuclear translocation, as well as decreased protein levels of pro-inflammatory cytokines, TNF-α, IL-1β and IL-6. Further, MaR1 treatment restored PSD95 and synapsin II levels, suggesting that MarR1 also protected synaptic integrity.ConclusionOur results indicate that MaR1 ameliorates the SNL-induced neuropathic pain by regulating glial activities and pro-inflammatory cytokines release. The present study offers insight into the potential of MaR1 as a novel intervention to ameliorate neuropathic pain.

The Anti-Inflammatory Role of Omega-3 Polyunsaturated Fatty Acids Metabolites in Pre-Clinical Models of Psychiatric, Neurodegenerative, and Neurological Disorders

“…In a model of inflammatory pain, RvDs and RvEs were found to reduce pain behaviors through central actions (33). Additionally, maresins have been demonstrated to attenuate mechanical allodynia (34,35), a process involving central sensitization, and decreased levels of IL-1β, IL-6, and TNF-α in spinal cord tissue in models of neuropathic pain. Taken together, these findings therefore suggest the potential involvement of SPMs in other disorders within the CNS.…”

The specialised pro‐resolving lipid mediator maresin 1 reduces inflammatory pain with a long‐lasting analgesic effect

“…Furthermore, in a model of spinal cord injury, the endogenous production of MaR1 begins only 14 days after injury, and exogenous administration of it at early time points induces spinal cord recovery, indicating neuroprotective and pro-resolving effects (Francos-Quijorna et al, 2017). MaR1 also demonstrates analgesic activity in different models of pain (Gao et al, 2018;Park, 2015;Serhan et al, 2012;Zhang et al, 2018).…”

Gabexate mesilate ameliorates the neuropathic pain in a rat model by inhibition of proinflammatory cytokines and nitric oxide pathway via suppression of nuclear factor-κB

“…with potent therapeutic effects according to its developmental mechanism [1]. Not only the changes in the nervous systems, but also neuroinflammation, are associated with the development of neuropathic pain [2].…”