Zaprinast diminished pain and enhanced opioid analgesia in a rat neuropathic pain model

Rojewska, Ewelina; Piotrowska, Anna; Jurga, Agnieszka M.; Makuch, Wioletta; Mika, Joanna

doi:10.1016/j.ejphar.2018.09.001

Cited by 13 publications

(10 citation statements)

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“…In our study, a CCR1 antagonist reduced spinal microglial/macrophage activation, similarly to other substances that weakened neuropathic pain‐related symptoms, e.g. minocycline, gabapentin, zaprinast, maraviroc (CCR5 antagonist) and RS504393 (CCR2 antagonist) . In turn, the role of GFAP‐positive cells (astroglia and satellite cells) in neuropathy is still unclear, some studies suggest that they can promote protective functions in neuropathic pain .…”

Section: Discussionsupporting

confidence: 56%

“…minocycline, gabapentin, zaprinast, maraviroc (CCR5 antagonist) and RS504393 (CCR2 antagonist). 6,13,15,74,75 In turn, the role of GFAP-positive cells (astroglia and satellite cells) in neuropathy is still unclear, some studies suggest that they can promote protective functions in neuropathic pain. 40,76,77 The immunostaining against GFAP shows that astroglial cells (at the spinal cord level) and satellite cells (at DRG level) are also activated after sciatic nerve injury.…”

Section: Discussionmentioning

confidence: 99%

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The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

et al. 2020

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Summary A growing body of evidence has indicated that the release of nociceptive factors, such as interleukins and chemokines, by activated immune and glial cells has crucial significance for neuropathic pain generation and maintenance. Moreover, changes in the production of nociceptive immune factors are associated with low opioid efficacy in the treatment of neuropathy. Recently, it has been suggested that CC chemokine receptor type 1 (CCR1) signaling is important for nociception. Our study provides evidence that the development of hypersensitivity in rats following chronic constriction injury (CCI) of the sciatic nerve is associated with significant up‐regulation of endogenous CCR1 ligands, namely, CCL2, CCL3, CCL4, CCL6, CCL7 and CCL9 in the spinal cord and CCL2, CCL6, CCL7 and CCL9 in dorsal root ganglia (DRG). We showed that single and repeated intrathecal administration of J113863 (an antagonist of CCR1) attenuated mechanical and thermal hypersensitivity. Moreover, repeated administration of a CCR1 antagonist enhanced the analgesic properties of morphine and buprenorphine after CCI. Simultaneously, repeated administration of J113863 reduced the protein levels of IBA‐1 in the spinal cord and MPO and CD4 in the DRG and, as a consequence, the level of pronociceptive factors, such as interleukin‐1β (IL‐1β), IL‐6 and IL‐18. The data obtained provide evidence that CCR1 blockade reduces hypersensitivity and increases opioid‐induced analgesia through the modulation of neuroimmune interactions.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

et al. 2020

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“…The G-protein-coupled receptor GPR35 is expressed in glia and neurons of the hippocampus (Berlinguer-Palmini et al 2013;Alkondon et al 2015). When activated they inhibit adenylate cyclase and depress pain-induced behaviours (Rojewska et al, 2018;Cosi et al 2011;Moroni 2012;Resta et al 2016). On neurons, they depress excitability and synaptic transmission in the hippocampus (Alkondon et al 2011) and dorsal root ganglia, where they depress N-type calcium channels (Guo et al, 2008;Ohshiro et al 2008) possibly mediated by Hyperpolarisation-activated-Cyclic Nucleotide-gated ion channels (Resta et al 2016).…”

Section: Assessing Reproducibilitymentioning

confidence: 99%

Does kynurenic acid act on nicotinic receptors? An assessment of the evidence

Stone

2019

Journal of Neurochemistry

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As a major metabolite of kynurenine in the oxidative metabolism of tryptophan, kynurenic acid is of considerable biological and clinical importance as an endogenous antagonist of glutamate in the central nervous system. It is most active as an antagonist at receptors sensitive to N‐methyl‐D‐aspartate (NMDA) which regulate neuronal excitability and plasticity, brain development and behaviour. It is also thought to play a causative role in hypo‐glutamatergic conditions such as schizophrenia, and a protective role in several neurodegenerative disorders, notably Huntington’s disease. An additional hypothesis, that kynurenic acid could block nicotinic receptors for acetylcholine in the central nervous system has been proposed as an alternative mechanism of action of kynurenate. However, the evidence for this alternative mechanism is highly controversial, partly because at least eight earlier studies concluded that kynurenic acid blocked NMDA receptors but not nicotinic receptors and five subsequent, independent studies designed to repeat the results have failed to do so. Many studies considered to support the alternative ‘nicotinic’ hypothesis have been based on the use of analogs of kynurenate such as 7‐chloro‐kynurenic acid, or putatively nicotinic modulators such as galantamine, but a detailed analysis of the pharmacology of these compounds suggests that the results have often been misinterpreted, especially since the pharmacology of galantamine itself has been disputed. This review examines the evidence in detail, with the conclusion that there is no confirmed, reliable evidence for an antagonist activity of kynurenic acid at nicotinic receptors. Therefore, since there is overwhelming evidence for kynurenate acting at ionotropic glutamate receptors, especially NMDAR glutamate and glycine sites, with some activity at GPR35 sites and Aryl Hydrocarbon Receptors, results with kynurenic acid should be interpreted only in terms of these confirmed sites of action.

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“…injection 35 . In a rat model of neuropathic pain, intrathecal administration of Zaprinast diminished pain symptoms and increased the effectiveness of opioids 36 . IP injection of Zaprinast or KYNA in rats also attenuates PGE2-induced thermal hyperalgesia 37 .…”

Section: Discussionmentioning

confidence: 97%

Activation of the G-protein coupled receptor GPR35 by human milk oligosaccharides through different pathways

Foata

Sprenger

Rochat

et al. 2020

Sci Rep

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Numerous benefits of breastfeeding over infant formula are fully established. The superiority of human milk over bovine milk-based formula is partly due to human milk oligosaccharides (HMOs), a family of over 100 molecules present specifically and substantially in human milk that resemble mucosal glycans. To uncover novel physiological functions and pathways of HMOs, we screened a panel of 165 G-protein coupled receptors (GPCRs) using a blend of 6 HMOs (3′-O-sialyllactose (3′SL), 6′-O-sialyllactose (6′SL), lacto-N-tetraose (LNT), lacto-N-neo-tetraose (LNnT), 2-O-fucosyllactose (2′FL), and difucosyllactose (diFL)), and followed up positive hits with standard receptor assays. The HMO blend specifically activated GPR35. LNT and 6′SL individually activated GPR35, and they showed synergy when used together. In addition, in vitro fermentation of infant stool samples showed that 2′FL upregulates the production of the GPR35 agonist kynurenic acid (KYNA) by the microbiota. LNT + 6′SL and KYNA showed additive activation of GPR35. Activation by 6′SL and LNT of GPR35, a receptor mediating attenuation of pain and colitis, is to our knowledge the first demonstration of GPCR activation by any HMO. In addition, we demonstrated a remarkable cooperation between nutrition and microbiota towards activation of a host receptor highlighting the close interplay between environment and host-microbe interactions.

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Zaprinast diminished pain and enhanced opioid analgesia in a rat neuropathic pain model

Cited by 13 publications

References 100 publications

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

The blockade of CC chemokine receptor type 1 influences the level of nociceptive factors and enhances opioid analgesic potency in a rat model of neuropathic pain

Does kynurenic acid act on nicotinic receptors? An assessment of the evidence

Activation of the G-protein coupled receptor GPR35 by human milk oligosaccharides through different pathways

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