Resolvins RvE1 and RvD1Attenuate Inflammatory Pain via Central and Peripheral Actions

By Zhen-Zhong Xu, Ling Zhang, Tong Liu, J. Park, T. Berta, Rong Yang, C. Serhan, R. Ji. Nature Medicine, 2010

601 citations recorded by the source corpus.

Inflammatory pain, such as arthritis pain, is a growing health problem. Inflammatory pain is generally treated with opioids and cyclooxygenase (COX) inhibitors, but both are limited by side effects. Recently, resolvins, a unique family of lipid mediators, including RvE1 and RvD1 derived from omega-3 polyunsaturated fatty acid, have shown marked potency in treating disease conditions associated with inflammation. Here we report that peripheral (intraplantar) or spinal (intrathecal) administration of RvE1 or RvD1 in mice potently reduces inflammatory pain behaviors induced by intraplantar injection of formalin, carrageenan or complete Freund's adjuvant (CFA), without affecting basal pain perception. Intrathecal RvE1 injection also inhibits spontaneous pain and heat and mechanical hypersensitivity evoked by intrathecal capsaicin and tumor necrosis factor-α (TNF-α). RvE1 has anti-inflammatory activity by reducing neutrophil infiltration, paw edema and proinflammatory cytokine expression. RvE1 also abolishes transient receptor potential vanilloid subtype-1 (TRPV1)- and TNF-α–induced excitatory postsynaptic current increases and TNF-α–evoked N-methyl-D-aspartic acid (NMDA) receptor hyperactivity in spinal dorsal horn neurons via inhibition of the extracellular signal–regulated kinase (ERK) signaling pathway. Thus, we show a previously unknown role for resolvins in normalizing the spinal synaptic plasticity that has been implicated in generating pain hypersensitivity. Given the potency of resolvins and the well-known side effects of opioids and COX inhibitors, resolvins may represent new analgesics for treating inflammatory pain.

Subfields: Biochemistry, Nutrition and Dietetics, Pharmacology

View Paper: https://www.semanticscholar.org/paper/652290ea1a94867739110daa5dc141df7c9c415d

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In Biochemistry

1. B. Levy
2. M. Basil
3. C. Serhan
4. P. Calder
5. T. Kern
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In Nutrition and Dietetics

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2. M. Basil
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Citations in the corpus

• Interactions between the immune and nervous systems in pain (2010, background): “Once activated by injury, immune and immune-related cells such as keratinocytes and vascular endothelial cells also synthesize and secrete anti-inflammatory cytokines, proresolution lipid mediators and opioid peptides to suppress pai”
• Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. (2018, background): “Since it was first demonstrated that RvE1 and RvD1 are potent in resolving inflammatory and postoperative pain (133, 134) and that their receptors can regulate transient receptor potential (TRP) ion channels and spinal cord synaptic transmission, addi-”
• Specialized pro-resolving mediators: endogenous regulators of infection and inflammation (2015, background): “Of note, mouse models have suggested a role for RvD1, RvE1, neuroprotectin D1 (NPD1) and MaR1 in attenuating pain by inhibition of TRP channels [125] [126] [127] [128] .”