Celecoxib reverts oxaliplatin-induced neuropathic pain through inhibiting PI3K/Akt2 pathway in the mouse dorsal root ganglion

Jiang, Shuping; Zhang, Zhendong; Kang, Lumei; Wang, Qinghua; Zhang, Lei; Chen, Hongping

doi:10.1016/j.expneurol.2015.11.001

Cited by 46 publications

(30 citation statements)

References 40 publications

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“…It is also well established that the PI3K/Akt pathway modulates nociceptive information and mediates the central sensitization induced by a noxious stimuli [190-194]. The inhibition of PI3K significantly attenuates inflammatory and neuropathic pain [175,195-201]. Recent studies have revealed an important role of the PI3K/Akt cascade in the functions of microglial cells.…”

Section: Phosphoinositide 3-kinase (Pi3k)/aktmentioning

confidence: 99%

Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain

Popiołek-Barczyk¹,

Mika

2016

CMC

145

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The microglia, once thought only to be supporting cells of the central nervous system (CNS), are now recognized to play essential roles in many pathologies. Many studies within the last decades indicated that the neuro-immune interaction underlies the generation and maintenance of neuropathic pain. Through a large number of receptors and signaling pathways, the microglial cells communicate with neurons, astrocytes and other cells, including those of the immune system. A disturbance or loss of CNS homeostasis causes rapid responses of the microglia, which undergo a multistage activation process. The activated microglia change their cell shapes and gene expression profiles, which induce proliferation, migration, and the production of pro- or antinociceptive factors. The cells release a large number of mediators that can act in a manner detrimental or beneficial to the surrounding cells and can indirectly alter the nociceptive signals. This review discusses the most important microglial intracellular signaling cascades (MAPKs, NF-κB, JAK/STAT, PI3K/Akt) that are essential for neuropathic pain development and maintenance. Our objective was to identify new molecular targets that may result in the development of powerful tools to control the signaling associated with neuropathic pain.

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Section: Phosphoinositide 3-kinase (Pi3k)/aktmentioning

confidence: 99%

Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain

Popiołek-Barczyk¹,

Mika

2016

CMC

145

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“…Many studies have focused on the side effects of OXA in the dorsal root ganglion (DRG), which contains the cell bodies of the primary sensory neurons responsible for transduction and modulation of sensory information and transmission of it to the spinal cord 5 , 6 . Our previous research also indicate that celecoxib alleviates OXA-induced neuropathic pain through inhibiting of the PI3K/Akt2 pathway in the mouse DRG 7 . Recently, an increasing number of data suggested that spinal pathological responses are evoked by OXA, contributing to hyperalgesia.…”

Section: Introductionmentioning

confidence: 68%

“…COX-2, an inflammatory mediator, increases in the spinal cord dorsal horn neurons following L5 spinal nerve ligation 25 . Our previous data show that OXA can increase the expression of COX-2 in the DRG 7 . In the present study, we also found that OXA increased the COX-2 mRNA expression in the spinal dorsal horn.…”

Section: Discussionmentioning

confidence: 84%

“…The mice in the vehicles and the OXA+vehicle groups were delivered the same volume of 0.5% methylcellulose according to the procedure for the OXA+celecoxib group. The dosage of celecoxib (30 mg/kg/day) was chosen according to a previous report 7 . This dose of celecoxib was an effective level against the neuropathic pain-induced by OXA.…”

Section: Methodsmentioning

confidence: 99%

“…Based on the OXA concentration used, there are generally two ways to induce hyperalgesia: long-term treatment with a low dose of OXA for 15 , 16 and short-term treatment with high dose of OXA 7 , 17 . In this study, the dosage of OXA was chosen according to a previous report 6 .…”

Section: Methodsmentioning

confidence: 99%

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Celecoxib alleviates oxaliplatin-induced hyperalgesia through inhibition of spinal ERK1/2 signaling

et al. 2016

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Numerous pieces of evidence have revealed that oxaliplatin (OXA) evokes mechanical and cold hypersensitivity. However, the mechanism underlying these bothersome side effects needs to be further investigated. It is well known that cyclooxygenase-2 (COX-2) and extracellular signal-regulated kinases (ERK1/2) signaling play crucial roles in several pain states. Our previous data showed that Akt2 in the dorsal root ganglion (DRG) participated in the regulation of OXA-induced neuropathic pain. But it is still unclear whether spinal ERK1/2 signaling is involved in the regulation of OXA-induced hyperalgesia, and the linkage between COX-2 and ERK1/2 signaling in mediating OXA-induced hyperalgesia also remains unclear. In this research, we investigated the possible mechanism of celecoxib, a COX-2 inhibitor, in OXA-induced neuropathic pain. Our results show that single dose of OXA (12 mg/kg) significantly attenuated both the tail withdrawal latency (TWL) and mechanical withdrawal threshold (MWT) at days 4 after the OXA treatment. Administration of celecoxib (30 mg/kg/day) for 4 and 6 days inhibited the decrease in TWL and MWT, and each was significantly higher than that of the OXA+vehicle group and was equivalent to that of the vehicles group. OXA increased the expression of cyclooxygenase-2 (COX-2) mRNA and phosphorylated extracellular signal-regulated kinase1/2 (pERK1/2) protein in the lumbar 4-5 (L4-5) spinal cord dorsal horn neurons. Administration of celecoxib for 7 days suppressed the increase in expression of COX-2 and pERK1/2 induced by OXA. Our findings suggested that COX-2 and ERK1/2 signaling in spinal cord contributed to the OXA-induced neuropathic pain.

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Isobolographic Analyses of Proglumide–Celecoxib Interaction in Rats with Painful Diabetic Neuropathy

Suárez-Méndez

Tovilla‐Zárate

Ortega-Varela

et al. 2017

Drug Development Research

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Preclinical Research The aim of the present study was to analyze the antihyperalgesic and antiallodynic interaction between the non-selective cholecystokinin (CCK) antagonist receptor, proglumide, and the selective cyclooxygenase-2 inhibitor, celecoxib in streptozotocin (STZ)-induced diabetic rats. Hyperalgesia was evaluated in the formalin test and tactile allodynia using von Frey filaments. Isobolographic analyses were employed to define the nature of the compound interactions, using a fixed dose ratio (0.5:0.5). Proglumide (20-160 mg/kg) and celecoxib (0.3-30 mg/kg) in these fixed dose ratio combinations induced dose-dependent antihyperalgesia and an antiallodynic effect in diabetic rats. ED values were calculated for the treatments and an isobologram was constructed. Theoretical ED values for combination proglumide-celecoxib estimated from the isobolograms for antihyperalgesic and antiallodynic activity (30.50 ± 1.90 mg/kg and 45.81 ± 4.55 mg/kg, respectively) were obtained, while experimental ED values for this antihyperalgesic and antiallodynic combined effect (13.83 ± 0.65 mg/kg and 17.74 ± 3.57 mg/kg; respectively) were significantly different. Coadministration of proglumide-celecoxib showed an interaction index value of 0.45 ± 0.03 for the antihyperalgesic effect and 0.39 ± 0.08 for the antiallodynic activity, indicating a synergistic interaction. These data suggest that proglumide and celecoxib can interact synergistically to reduce hyperalgesic and allodynic behaviors in diabetic neuropathy. This combination could be useful to treat neuropathic pain in diabetic patients. Drug Dev Res 78 : 116-123, 2017. ©2017 Wiley Periodicals, Inc.

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Celecoxib reverts oxaliplatin-induced neuropathic pain through inhibiting PI3K/Akt2 pathway in the mouse dorsal root ganglion

Cited by 46 publications

References 40 publications

Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain

Targeting the Microglial Signaling Pathways: New Insights in the Modulation of Neuropathic Pain

Celecoxib alleviates oxaliplatin-induced hyperalgesia through inhibition of spinal ERK1/2 signaling

Isobolographic Analyses of Proglumide–Celecoxib Interaction in Rats with Painful Diabetic Neuropathy

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