The antihyperalgesic effect of docosahexaenoic acid in streptozotocin-induced neuropathic pain in the rat involves the opioidergic system

Landa-Juárez, Arizai Yolia; Pérez-Severiano, Francisca; Castañeda‐Hernández, Gilberto; Ortiz, Mario I.; Chávez-Piña, Aracely Evangelina

doi:10.1016/j.ejphar.2018.12.029

Cited by 9 publications

(3 citation statements)

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“…Interestingly, we observed an enhanced expression and activity of phospholipase 2 after SAFit2 treatment, which resulted in an increase of free polyunsaturated fatty acids and especially of the omega-3 PUFA DHA. These results further confirm our previously suggested SAFit2-mediated anti-inflammatory lipid profile, as DHA was shown to reduce neuropathic pain in a diabetic rat model as well as in a nerve injury rat and mouse model [ 62 ]. Moreover, studies reported that DHA has a protective effect on microglia and astrocytes as it counteracts oxidative stress induced calcium dysregulations and ER stress [ 63 , 64 ].…”

Section: Discussionsupporting

confidence: 90%

SAFit2 ameliorates paclitaxel-induced neuropathic pain by reducing spinal gliosis and elevating pro-resolving lipid mediators

Wedel

Hahnefeld

Schreiber

et al. 2023

J Neuroinflammation

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Background Chemotherapy-induced neuropathic pain (CIPN) describes a pathological pain state that occurs dose-dependently as a side effect and can limit or even impede an effective cancer therapy. Unfortunately, current treatment possibilities for CIPN are remarkably confined and mostly inadequate as CIPN therapeutics themselves consist of low effectiveness and may induce severe side effects, pointing out CIPN as pathological entity with an emerging need for novel treatment targets. Here, we investigated whether the novel and highly specific FKBP51 inhibitor SAFit2 reduces paclitaxel-induced neuropathic pain. Methods In this study, we used a well-established multiple low-dose paclitaxel model to investigate analgesic and anti-inflammatory properties of SAFit2. For this purpose, the behavior of the mice was recorded over 14 days and the mouse tissue was then analyzed using biochemical methods. Results Here, we show that SAFit2 is capable to reduce paclitaxel-induced mechanical hypersensitivity in mice. In addition, we detected that SAFit2 shifts lipid levels in nervous tissue toward an anti-inflammatory and pro-resolving lipid profile that counteracts peripheral sensitization after paclitaxel treatment. Furthermore, SAFit2 reduced the activation of astrocytes and microglia in the spinal cord as well as the levels of pain-mediating chemokines. Its treatment also increased anti-inflammatory cytokines levels in neuronal tissues, ultimately leading to a resolution of neuroinflammation. Conclusions In summary, SAFit2 shows antihyperalgesic properties as it ameliorates paclitaxel-induced neuropathic pain by reducing peripheral sensitization and resolving neuroinflammation. Therefore, we consider SAFit2 as a potential novel drug candidate for the treatment of paclitaxel-induced neuropathic pain.

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Section: Discussionsupporting

confidence: 90%

SAFit2 ameliorates paclitaxel-induced neuropathic pain by reducing spinal gliosis and elevating pro-resolving lipid mediators

Wedel

Hahnefeld

Schreiber

et al. 2023

J Neuroinflammation

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“…Studies evaluating interactions in analgesic and anti-inflammatory models have been the most common. As such, previous studies have demonstrated that DHA possesses antiinflammatory and analgesic properties (Nakamoto et al, 2010;Landa-Juárez et al, 2016;Landa-Juárez et al, 2019). Moreover, it has been reported that DHA has a pharmacological interaction with NSAIDs, such as indomethacin and naproxen, that results in a synergistic antinociceptive effect (Arroyo-Lira et al, 2014;Arroyo-Lira et al, 2017).…”

Section: Discussionmentioning

confidence: 94%

Synergistic protective effects between docosahexaenoic acid and omeprazole on the gastrointestinal tract in the indomethacin‐induced injury model

Sánchez-Trigueros

Méndez-Cruz

Pineda-Peña³

et al. 2020

Drug Development Research

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Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs due to their antipyretic, anti-inflammatory, and analgesic properties. However, NSAIDs can cause adverse reactions, mainly gastrointestinal damage. Omeprazole (OMP) exhibits gastroprotective activity, but its protection is limited at the intestinal level. For this reason, it is essential to utilize a combination of therapies that provide fewer adverse effects, such as the combined treatment of OMP and docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid with anti-inflammatory, analgesic, and gastroprotective activities. The objective of this study was to evaluate the pharmacological interaction between DHA and OMP in a murine model of indomethacin-induced gastrointestinal damage. The gastroprotective and enteroprotective effects of DHA (0.3-10 mg/kg, p.o.), OMP (1-30 mg/kg, p.o.), or the combination treatment of both compounds (3-56.23 mg/kg, p.o.) were evaluated in the indomethacin-induced gastrointestinal damage model (30 mg/kg, p.o.). Since DHA and OMP exhibited a protective effect in a dose-responsive fashion, the ED 30 for each individual compound was determined and a 1:1 combination of DHA and OMP was tested. Isobolographic analysis was used to determine any pharmacodynamic interactions. Since the effective experimental dose ED 30 (Zexp) of the combined treatment of DHA and OMP was lower than the theoretical additive dose (Zadd; p < .05) in both the stomach and small intestine their protective effects were considered synergistic. These results indicate that the synergistic protective effects from combined treatment of DHA and OMP could be ideal for mitigating damage generated by NSAIDs at the gastrointestinal level.

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“…These actions cause both presynaptic inhibition of neurotransmitter release from the central endings of small-diameter primary afferent fibers and postsynaptic inhibition of membrane depolarization of nociceptive dorsal horn neurons ( Stein, 2016 ). Previous studies demonstrated the participation of opioid receptors in the local peripheral antinociception produced by several non-opioid drugs, such as diclofenac, dipyrone, docosahexaenoic acid, or pamabrom ( Silva et al, 2016 ; Landa-Juárez et al, 2019 ; Ortiz et al, 2022 ). However, the activation probable of opioid receptors in the α -Bisabolol induced-antinociception was disqualified ( Melo et al, 2017 ; Ortiz et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Synergistic interaction and activation of the opioid receptor-NO–cGMP–K+ channel pathway on peripheral antinociception induced by the α-Bisabolol-diclofenac combination

Ortiz

2023

Front. Pharmacol.

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Introduction: The local peripheral combination of analgesic drugs with herbal derivatives may have beneficial effects. Information on the action mechanism of these interactions between drugs is scarce. Therefore, the main of the present study was to determine the pharmacological interaction and action mechanism of the combination α-Bisabolol and diclofenac.Methods: Rats were injected in the dorsal surface of the right hind paw with 1% formalin. Rats received subcutaneous injections in the dorsal surface of paw of vehicles or increasing doses of α-Bisabolol, diclofenac or their combination before formalin injection into the paw. Antinociception of the α-Bisabolol + diclofenac combination was evaluated with and without the local treatment of naloxone, metformin, NG-nitro-L-arginine methyl ester (L-NAME), 1H- (1,2,4)-oxadiazolo (4,2-a) quinoxalin-1-one (ODQ), glibenclamide, glipizide, 4-aminopyridine, tetraethylammonium, apamin, or charybdotoxin.Results: α-Bisabolol, diclofenac or α-Bisabolol-diclofenac combinations produced significant antinociception in the rat (p < 0.05). The experimental effective dose (ED) value of 109.2 µg/paw was different significantly of the theoretical effective dose (ED) of 245.7 µg/paw (synergism). Blockers significantly reverted the antinociception produced by the synergistic combination of α-Bisabolol and diclofenac.Discussion: Data showed a synergism of the α-Bisabolol-diclofenac combination and the activation of the opioid receptor-Nitric Oxide–cyclic GMP–K+ channels pathway and a biguanide-dependent mechanism in order to produce the potentiation of its peripheral antinociception in the formalin test.

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The antihyperalgesic effect of docosahexaenoic acid in streptozotocin-induced neuropathic pain in the rat involves the opioidergic system

Cited by 9 publications

References 50 publications

SAFit2 ameliorates paclitaxel-induced neuropathic pain by reducing spinal gliosis and elevating pro-resolving lipid mediators

SAFit2 ameliorates paclitaxel-induced neuropathic pain by reducing spinal gliosis and elevating pro-resolving lipid mediators

Synergistic protective effects between docosahexaenoic acid and omeprazole on the gastrointestinal tract in the indomethacin‐induced injury model

Synergistic interaction and activation of the opioid receptor-NO–cGMP–K+ channel pathway on peripheral antinociception induced by the α-Bisabolol-diclofenac combination

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