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Review
. 2023 Sep 27;16(10):1366.
doi: 10.3390/ph16101366.

Role of Resolvins in Inflammatory and Neuropathic Pain

Jaeik Park  1 , Jueun Roh  1 , Jingying Pan  1   2 , Yong Ho Kim  1 , Chul-Kyu Park  1 , Youn Yi Jo  3
Affiliations
Review

Role of Resolvins in Inflammatory and Neuropathic Pain

Jaeik Park et al. Pharmaceuticals (Basel). .

Abstract

Chronic pain is an unpleasant experience associated with actual or potential tissue damage. Inflammatory pain alerts the body to inflammation and promotes healing; however, unresolved inflammation can lead to chronic pain. Conversely, neuropathic pain, due to somatosensory damage, can be a disease in itself. However, inflammation plays a considerable role in the progression of both types of pain. Resolvins, derived from omega-3 fatty acids, actively suppress pro-inflammatory mediators and aid in the resolution of inflammation. Resolvins alleviate various inflammatory and neuropathic pain models by reducing hypersensitivity and regulating inflammatory cytokines and glial activation in the spinal cord and dorsal root ganglia. Thus, resolvins are a promising alternative for pain management with the potential to reduce the side effects associated with conventional medications. Continued research is crucial to unlock the therapeutic potential of resolvins and integrate them into effective clinical pain management strategies. This review aimed to evaluate the literature surrounding the resolvins in inflammatory and neuropathic pain.

Keywords: dorsal root ganglia; inflammation; inflammatory pain; neuropathic pain; pain management; resolvin; spinal cord.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic of D-series resolvins biosynthesis and enzymatic pathway. RvDs are synthesized from DHA via several types of LOX and LTA4H. 17(S)-HDHA converted from DHA is oxidized into two hydroperoxyl intermediates via LOX5, which can be converted into three types of RvDs. RvD1, RvD2, and RvD5 are synthesized from 7(S)-Hp-17(S)-HDHA. RvD3, RvD4, and RvD6 are synthesized from 4(S)-Hp-17(S)-HDHA. 17(S)-HDHA, 17(S)-hydroxy DHA; 4(S)-Hp-17(S)-HDHA, 4(S)-hydroperoxy-17(S)-HDHA; 7(S)-Hp-17(S)-HDHA, 7(S)-hydroperoxy-17(S)-HDHA DHA, docosahexaenoic acid; LOX, lipoxygenase; LTA4H, leukotriene A4 hydrolase; RvDs, D-series Rvs; RvDn, Rv Dn (n = 1~6).
Figure 2
Figure 2
Schematic of E-series resolvins biosynthesis and enzymatic pathway. RvEs are synthesized from EPA. RvE1 and RvE2 are converted from 5(S)-Hp-18(R)-HEPE. EPA may be oxidated to RvE3 or 15(5)-H(p)EPE via LOX15. 15(5)-H(p)EPE is converted into RvE4 through 15(S)-hydroxy-5(S)-H(p)EPE. 18(R)-HEPE, 18(R)-hydroxy EPA; 5(S)-Hp-18(R)-HEPE, 5(S)-hydroperoxy-18(S)-HEPE; 15(S)-H(p)EPE, 15(S)-hydroperoxy EPA; COX-2, cyclooxygenase-2; EPA, eicosapentaenoic acid; RvEs, E-series Rvs; Rv En (n = 1~4).
Figure 3
Figure 3
Pro-resolving and inflammatory function of resolvins. Rvs are known to induce the resolution of inflammatory reactions through various mechanisms; they inhibit the expression of pro-inflammatory factors, promote the expression of anti-inflammatory factors, induce class switching of macrophages, restore tissue homeostasis, relieve neuroinflammation, and clear inflammatory immune cells or senescent red blood cells. On the contrary, RvDs promote the phagocytic function of macrophages.
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