Table 1.
Summary of therapeutic potential of quercetin in chronic pain.
| Model | Treatment Strategy | Effects | Mechanisms | References |
|---|---|---|---|---|
| Carrageenan-induced inflammatory pain rats | PEA-Q (10 and 20 mg/kg, i.g.) was administered 30 min before carrageenan injection. | PWL↑ | MPO↓ | [8] |
| Formalin-induced inflammatory pain mice Capsaicin-induced inflammatory pain mice |
Quercetin (10-60 mg/kg, i.p. or 100-500 mg/kg, i.g.) was administered on 30 minutes before formalin or capsaicin injection | PWL↑ | Activation of GABAergic system Activation of 5-HT receptors |
[21] |
| Formalin-induced inflammatory pain mice Carrageenan-induced inflammatory pain mice |
Quercetin (3, 10, 30 and 100 mg/kg, i.p. or 30, 100 and 300 mg/kg, i.g.) was administered on 30 minutes before formalin or capsaicin injection | PWL↑ | IL-1β↓ GSH↓ |
[60] |
| MSU-induced gout arthritis pain mice | Quercetin (10, 30 and 100 mg/kg, s.c.) was administered on 30 minutes before MSU injection. | PWT↑ | Activation of opioidergic system Leukocyte recruitment↓ NF-κB, TNF-α, IL-1β↓ NLRP3, ASC, pro-caspase-1↓ GSH, FRAP, ABTS↑ Superoxide anion, gp91phox↓ |
[53] |
| TiO2-induced arthritis pain mice | Quercetin (10, 30 and 100 mg/kg, i.p.) was administered once daily for 30 days starting from the first day after TiO2 injection. | PWT↑ | Leukocyte recruitment↓ Neutrophil recruitment↓ TNF-α, IL-1β, IL-6, COX2↓ GSH, FRAP, ABTS↑ Superoxide anion, gp91phox↓ Nrf2, HO-1↑ |
[7] |
| MIA-induced osteoarthritis pain rats | PEA-Q (10 and 20 mg/kg, i.g.) was administered three times per week for 21 days starting from the third day after MIA injection. | PWT↑ PWL↑ |
TNF-α, IL-1β, NGF↓ MMP1, MMP3, MMP9↓ |
[8] |
| CCI-induced neuropathic pain rats | Quercetin (100 mg/kg, i.p.) was administered at 21 days after CCI surgery. Quercetin (100 mg/kg, i.p.) was administered for 4 consecutive days before CCI surgery. Quercetin (100 mg/kg, i.p.) was administered for 4 consecutive days after CCI surgery. |
PWT↑ PWL↑ |
/ | [16] |
| CCI-induced neuropathic pain rats | Quercetin (30, 60 and 120 mg/kg, i.g.) was administered for 21 days starting from 7 days after CCI surgery. | PWT↑ PWL↑ |
Microglial activation↓ p-JNK, p-p38, p-ERK↓ TNF-α, IL-6, IL-1β↓ |
[65] |
| CCI-induced neuropathic pain rats | Quercetin (5.6, 17.8, 56.2, 177.8 and 316 mg/kg, s.c.) was administered on 10 days after CCI surgery. | PWT↑ PWL↑ |
/ | [20] |
| SNL-induced neuropathic pain rats | A single administration of quercetin (100 mg/kg, i.g.) was performed on 14 days after SNL surgery. Quercetin (100 mg/kg, i.g.) was administered for 14 days starting from 0 day after SNL surgery. Quercetin (100 mg/kg, i.g.) was administered for 14 days before SNL surgery. |
PWL↑ | TNF-α, IL-1β↓ MMP-9, MMP-2, CCL2↓ NF-κB, TAK1, JNK2↓ |
[33] |
| SNI-induced neuropathic pain rats | MF diet containing 1% or 0.1% quercetin was given from 4 days before SNI surgery until sacrifice. MF diet containing 1% quercetin was given from 7 days after SNI surgery. |
PWT↑ | Activation of satellite glial cells↓ p-STAT3↓ |
[48] |
| STZ-induced diabetic neuropathic pain rats | Quercetin (10 mg/kg, i.g.) was administered for 4 weeks starting from 21 days after STZ-injection. | PWL↑ | / | [2] |
| STZ-induced diabetic neuropathic pain rats | Quercetin (50 mg/kg, i.p.) was administered for 14 days starting from 7 days after STZ-injection. | PWT↑ PWL↑ |
Activation of satellite glial cells↓ P2X4 receptor↓ p38 MAPK↓ |
[64] |
| STZ-induced diabetic neuropathic pain mice | A single administration of quercetin (50 and 100 mg/kg, i.p.) was performed on 4 weeks after STZ injection. | PWL↑ | Activation of opioidergic system | [1] |
| Diabetic neuropathic pain in db/db mice | Quercetin (50 and 100 mg/kg, i.g.) was administered once daily for 8 weeks. | PWL↑ | Changes of synaptic morphology↓ PSD-95, synaptophysin↓ mTOR, p70S6K↓ |
[62] |
| Oxaliplatin-induced neuropathic pain mice | Quercetin (25, 50 and 100 mg/kg) was administered 30 minutes before every oxaliplatin injection. | PWT↑ PWL↑ |
MDA↓ Fos, nitrotyrosine, iNOS↓ |
[3] |
| Paclitaxel-induced neuropathic pain mice | Quercetin (20, and 60 mg/kg) was administered once daily starting from the first day after the first injection of paclitaxel for 40 days in rats. Quercetin (20, and 60 mg/kg) was administered once daily starting from the first day after the first injection of paclitaxel for 12 days in mice. |
PWT↑ PWL↑ |
PKCε, TRPV1↓ | [23] |
| Ethanol-induced neuropathic pain rats | Quercetin (10, 20 and 40 mg/kg, i.g.) was administered for 10 week starting from 1 hour before ethanol administration. | PWT↑ PWL↑ |
MDA, MPO, NO↓ DNA fragmentation↓ |
[51] |
| TCI-induced bone cancer pain mice | Quercetin (5, 10 and 20 mg/kg, i.g.) was administered once daily for 21 days starting from the first day after TCI. | PWT↑ | TNF-α, IL-1β↓ RANKL, RANK, OPG↓ PAR2, TRPV1↓ |
[38] |
| Ehrlich tumor-induced cancer pain mice | Quercetin (10, 30 and 100 mg/kg, i.p.) was administered on 8 days after injection of tumor cells. Quercetin (10, 30 and 100 mg/kg, i.p.) was administered once daily for 12 days after injection of tumor cells. |
PWT↑ PWL↑ |
Activation of opioidergic system Neutrophil recruitment↓ TNF-α, IL-1β↓ GSH, FRAP, ABTS↑ |
[12] |
Abbreviations: ABTS: free radical scavenging ability; ASC: C-terminal caspase recruitment domain; CCI: chronic constriction injury; CCL2: C-C Motif chemokine ligand 2; COX-2: cyclooxygenase 2; DNA: deoxyribonucleic acid; ERK: extracellular regulated protein kinases; 5-HT: 5-hydroxytryptamine; FRAP: ferric reducing ability potential; GSH: glutathione; HO-1: heme oxygenase-1; IL-1β: interleukin 1beta; IL-6: interleukin 6; i.g.: intragastrically; iNOS: inducible nitric oxide synthase; i.p.: intraperitoneally; i.t.: intrathecally; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; MDA: malondialdehyde; MIA: monoiodoacetate; MPO: myeloperoxidase; MMP: matrix metallopeptidase; MSU: monosodium urate crystals; mTOR: mammalian target of rapamycin; NF-κB: nuclear factor kappa B; NGF: nerve growth factor; NO: nitric oxide; NLRP3: NLR family pyrin domain containing 3; Nrf2: nuclear factor erythroid-2-related factor 2; OPG: osteoprotegerin; PAR2: protease-activated receptor 2; PEA-Q: palmitoylethanolamide-quercetin; PI3K: phosphoinositide 3-kinase; PSD-95: postsynaptic density protein-95; p70S6K: 70 kDa ribosomal protein S6 kinase; PWL: paw withdrawal latency; PWT: paw withdrawal threshold; RANKL: receptor activator of nuclear factor-kappa B ligand; RANK: receptor activator of nuclear factor-kappa B; SNI: spared nerve injury; SNL: spinal nerve ligation; s.c.: subcutaneously; STAT3: signal transducer and activator of transcription 3; STZ: streptozotocin; TAK1: TGF-β activated kinase 1; TCI: tumor cell implantation; TiO2: titanium dioxide; TNF-α: tumor necrosis factor α; TRPV1: transient receptor potential vanilloid 1; ↑: upregulated; ↓: downregulated.