The bivalent ligand MCC22 potently attenuates hyperalgesia in a mouse model of cisplatin-evoked neuropathic pain without tolerance or reward

Cataldo, Giuseppe; Erb, Samuel J.; Lunzer, Mary M.; Luong, Nhungoc; Akgün, Eyup; Portoghese, Philip S.; Olson, Julie K.; Simone, Donald A.

doi:10.1016/j.neuropharm.2019.04.004

Cited by 17 publications

(11 citation statements)

References 53 publications

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“…Regarding CDDP, Park and colleagues reported no increase of Iba-1 and GFAP positive glial cells in the lumbar spinal cord of CDDP-treated animals indicating no microglial and astrocyte activation ( 35 ). In contrast to these findings, spinal microglia (increase of Iba-1 immunoreactive cells), but not astrocytes, activation associated with an increased expression of pro-inflammatory cytokines such as IL-1β, IL-6 and TNF-α, and chemokine CCL3 were also reported ( 66 , 67 ). An increased expression of pro-inflammatory cytokines after CDDP treatment was confirmed also by other works ( 68 ).…”

Section: Introductionmentioning

confidence: 87%

Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy

et al. 2021

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Peripheral neuropathies are characterized by nerves damage and axonal loss, and they could be classified in hereditary or acquired forms. Acquired peripheral neuropathies are associated with several causes, including toxic agent exposure, among which the antineoplastic compounds are responsible for the so called Chemotherapy-Induced Peripheral Neuropathy (CIPN). Several clinical features are related to the use of anticancer drugs which exert their action by affecting different mechanisms and structures of the peripheral nervous system: the axons (axonopathy) or the dorsal root ganglia (DRG) neurons cell body (neuronopathy/ganglionopathy). In addition, antineoplastic treatments may affect the blood brain barrier integrity, leading to cognitive impairment that may be severe and long-lasting. CIPN may affect patient quality of life leading to modification or discontinuation of the anticancer therapy. Although the mechanisms of the damage are not completely understood, several hypotheses have been proposed, among which neuroinflammation is now emerging to be relevant in CIPN pathophysiology. In this review, we consider different aspects of neuro-immune interactions in several CIPN preclinical studies which suggest a critical connection between chemotherapeutic agents and neurotoxicity. The features of the neuroinflammatory processes may be different depending on the type of drug (platinum derivatives, taxanes, vinca alkaloids and proteasome inhibitors). In particular, recent studies have demonstrated an involvement of the immune response (both innate and adaptive) and the stimulation and secretion of mediators (cytokines and chemokines) that may be responsible for the painful symptoms, whereas glial cells such as satellite and Schwann cells might contribute to the maintenance of the neuroinflammatory process in DRG and axons respectively. Moreover, neuroinflammatory components have also been shown in the spinal cord with microglia and astrocytes playing an important role in CIPN development. Taking together, better understanding of these aspects would permit the development of possible strategies in order to improve the management of CIPN.

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Section: Introductionmentioning

confidence: 87%

Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy

et al. 2021

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“…MOR was implicated in microglial activation by morphine as shown by the use of selective MOR antagonists, microglia from global KO mice, and of RNA interference in microglia (Dutta et al, 2012;Gessi et al, 2016;Horvath & DeLeo, 2009;Merighi et al, 2012Merighi et al, , 2013. In addition, MOR was found to be expressed in adult spinal microglia in two studies (Cataldo et al, 2019;Horvath, Romero-Sandoval, & De Leo, 2010) but not in two other studies (Corder et al, 2017;Kao et al, 2012). Recently, we demonstrated, by the analysis of 47 transcriptomic data sets from both rodent and human microglia and by means of a novel reporter mouse line, that microglia express both Oprm1 mRNA and MOR protein (Maduna et al, 2018).…”

Section: Behavioral Data On the Role Of Microglial Mor In Vivo Corrob...mentioning

confidence: 98%

“…The bifunctional and biased MOR agonist KGFF09e which also blocks the neuropeptide FF anti-opioid system induces very potent analgesia without the above mentioned adverse effects (Drieu la Rochelle et al, 2018). The bivalent ligand MCC22 that is a MOR agonist and chemokine receptor CCR5 antagonist have very potent analgesic properties together with low adverse effects (Cataldo et al, 2019;Dutta et al, 2018). As microglia express chemokine receptors, the conditional MOR mutant animals may allow to further characterize these promising ligands.…”

Section: Microglial Mor and Mor-targeted Analgesiamentioning

confidence: 99%

Mu opioid receptor in microglia contributes to morphine analgesic tolerance, hyperalgesia, and withdrawal in mice

Reiss

Maduna

Maurin

et al. 2020

J of Neuroscience Research

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A major challenge in medicine is developing potent pain therapies without the adverse effects of opiates. Neuroinflammation and in particular microglial activation have been shown to contribute to these effects. However, the implication of the microglial mu opioid receptor (MOR) is not known. We developed a novel conditional knockout (cKO) mouse line, wherein MOR is deleted in microglia. Morphine analgesic tolerance was delayed in both sexes in cKO mice in the hot plate assay. Opioid-induced hyperalgesia (OIH) as measured in the tail immersion assay was abolished in male cKO mice, and physical dependence to morphine as assessed by naloxone-induced withdrawal was attenuated in female cKO mice. Our results show a sex-dependent contribution of microglial MOR in morphine analgesic tolerance, OIH, and physical dependence.In conclusion, our data suggest that blockade of microglial MOR could represent a therapeutic target for opiate analgesia without the opiate adverse effects.

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“…or i.t.) reduced mechanical hypersensitivity without pharmacological tolerance in a model of spontaneous inflammatory arthritis (Dutta et al, 2018) or in a model of chemotherapy induced peripheral neuropathy (Cataldo et al, 2019). MCC22 systemic administration (i.p.)…”

Section: Ligands Targeting Opioid Receptor Heteromersmentioning

confidence: 99%

Therapeutic potential of opioid receptor heteromers in chronic pain and associated comorbidities

Gaborit

Massotte

2022

British J Pharmacology

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Chronic pain affects 20 to 45% of the global population and is often associated with the development of anxio-depressive disorders. Treatment of this debilitating condition remains particularly challenging with opioids prescribed to alleviate moderate to severe pain. However, despite strong antinociceptive properties, numerous adverse effects limit opioid use in the clinic. Moreover, opioid misuse and abuse have become a major health concern worldwide. This prompted efforts to design original strategies that would efficiently and safely relieve pain. Targeting of opioid receptor heteromers is one of these. This review summarizes our current knowledge on the role of heteromers involving opioid receptors in the context of chronic pain and anxio-depressive comorbidities. It also examines how heteromerization in native tissue affects ligand binding, receptor signalling and trafficking properties. Finally, the therapeutic potential of ligands designed to specifically target opioid receptor heteromers is considered.

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The bivalent ligand MCC22 potently attenuates hyperalgesia in a mouse model of cisplatin-evoked neuropathic pain without tolerance or reward

Cited by 17 publications

References 53 publications

Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy

Neuroinflammatory Process Involved in Different Preclinical Models of Chemotherapy-Induced Peripheral Neuropathy

Mu opioid receptor in microglia contributes to morphine analgesic tolerance, hyperalgesia, and withdrawal in mice

Therapeutic potential of opioid receptor heteromers in chronic pain and associated comorbidities

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