Antihyperalgesic effect of CB1 receptor activation involves the modulation of P2X3 receptor in the primary afferent neuron

Oliveira, Maria Cláudia G.; Zanoni, Cristiane I.; Santos, Gilson Gonçalves dos; Manzo, Luis Paulo; Araldi, Dionéia; Bonet, Ivan José Magayewski; Tambeli, Cláudia Herrera; Dias, Elayne Vieira; Parada, Carlos Amílcar

doi:10.1016/j.ejphar.2017.01.030

Cited by 28 publications

(13 citation statements)

References 48 publications

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“…When anesthesia was stopped, rats regained consciousness, ϳ2 min after the intrathecal injection. Use of intrathecal AS-ODN to attenuate the expression of proteins, essential for their role in nociceptor sensitization, is well supported by previous studies (Song et al, 2009;Su et al, 2011;Bogen et al, 2012;Quanhong et al, 2012;Sun et al, 2013;Araldi et al, 2015Araldi et al, , 2016aAraldi et al, , 2017aFerrari et al, 2016;Oliveira-Fusaro et al, 2017).…”

Section: Odns As To Tlr4 and Pkc Mrnamentioning

confidence: 65%

Role of Nociceptor Toll-like Receptor 4 (TLR4) in Opioid-Induced Hyperalgesia and Hyperalgesic Priming

et al. 2019

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In addition to analgesia, opioids produce opioid-induced hyperalgesia (OIH) and neuroplasticity characterized by prolongation of inflammatory-mediator-induced hyperalgesia (hyperalgesic priming). We evaluated the hypothesis that hyperalgesia and priming induced by opioids are mediated by similar nociceptor mechanisms. In male rats, we first evaluated the role of nociceptor Toll-like receptor 4 (TLR4) in OIH and priming induced by systemic low-dose morphine (LDM, 0.03 mg/kg). Intrathecal oligodeoxynucleotide antisense to TLR4 mRNA (TLR4 AS-ODN) prevented OIH and prolongation of prostaglandin E 2 hyperalgesia (priming) induced by LDM. In contrast, high-dose morphine (HDM, 3 mg/kg) increased nociceptive threshold (analgesia) and induced priming, neither of which was attenuated by TLR4 AS-ODN. Protein kinase C (PKC) AS-ODN also prevented LDM-induced hyperalgesia and priming, whereas analgesia and priming induced by HDM were unaffected. Treatment with isolectin B4 (IB4)-saporin or SSP-saporin (which deplete IB4 ϩ and peptidergic nociceptors, respectively), or their combination, prevented systemic LDM-induced hyperalgesia, but not priming. HDM-induced priming, but not analgesia, was markedly attenuated in both saporin-treated groups. In conclusion, whereas OIH and priming induced by LDM share receptor and second messenger mechanisms in common, action at TLR4 and signaling via PKC, HDM-induced analgesia, and priming are neither TLR4 nor PKC dependent. OIH produced by LDM is mediated by both IB4 ϩ and peptidergic nociceptors, whereas priming is not dependent on the same population. In contrast, priming induced by HDM is mediated by both IB4 ϩ and peptidergic nociceptors. Implications for the use of low-dose opioids combined with nonopioid analgesics and in the treatment of opioid use disorder are discussed.

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Section: Odns As To Tlr4 and Pkc Mrnamentioning

confidence: 65%

Role of Nociceptor Toll-like Receptor 4 (TLR4) in Opioid-Induced Hyperalgesia and Hyperalgesic Priming

et al. 2019

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“…Rats recovered consciousness approximately 2 minutes after the injection. Of note, the attenuation of the expression of proteins involved in nociceptor sensitization by using intrathecal AS-ODNs has been previously demonstrated by several studies [5; 6; 8; 11; 25; 40; 46; 51-53].…”

Section: Methodsmentioning

confidence: 93%

Role of GPCR (mu-opioid)–receptor tyrosine kinase (epidermal growth factor) crosstalk in opioid-induced hyperalgesic priming (type II)

Araldi

Ferrari

Levine

2018

Pain

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Repeated stimulation of mu-opioid receptors (MORs), by an MOR-selective agonist DAMGO induces type II priming, a form of nociceptor neuroplasticity, which has 2 components: opioid-induced hyperalgesia (OIH) and prolongation of prostaglandin-E2 (PGE2)-induced hyperalgesia. We report that intrathecal antisense knockdown of the MOR in nociceptors, prevented the induction of both components of type II priming. Type II priming was also eliminated by SSP-saporin, which destroys the peptidergic class of nociceptors. Because the epidermal growth factor receptor (EGFR) participates in MOR signaling, we tested its role in type II priming. The EGFR inhibitor, tyrphostin AG 1478, prevented the induction of prolonged PGE2-induced hyperalgesia, but not OIH, when tested out to 30 days after DAMGO. However, even when repeatedly injected, an EGFR agonist did not induce hyperalgesia or priming. A phosphopeptide, which blocks the interaction of Src, focal adhesion kinase (FAK), and EGFR, also prevented DAMGO-induced prolongation of PGE2 hyperalgesia, but only partially attenuated the induction of OIH. Inhibitors of Src and mitogen-activated protein kinase (MAPK) also only attenuated OIH. Inhibitors of matrix metalloproteinase, which cleaves EGF from membrane protein, markedly attenuated the expression, but did not prevent the induction, of prolongation of PGE2 hyperalgesia. Thus, although the induction of prolongation of PGE2-induced hyperalgesia at the peripheral terminal of peptidergic nociceptor is dependent on Src, FAK, EGFR, and MAPK signaling, Src, FAK, and MAPK signaling is only partially involved in the induction of OIH.

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“…Ca 2+ influx through purinergic, carbachol-activating muscarinic or TRPV1 receptors increases anandamide synthesis within cells ( Ahluwalia et al, 2003 ) and activates both TRPV1 ( van der Stelt et al, 2005 ) and cannabinoid receptors. CB1 receptors co-localized with purinergic receptors in DRG small-diameter neurons control pain by anandamide and involves the modulation of P2X3 receptor in the primary afferent neuron ( Oliveira-Fusaro et al, 2017 ).…”

Section: Sensorial Stimuli From Drg To Central Projectionsmentioning

confidence: 99%

Cell Calcium Imaging as a Reliable Method to Study Neuron–Glial Circuits

2020

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Complex dynamic cellular networks have been studied in physiological and pathological processes under the light of single-cell calcium imaging (SCCI), a method that correlates functional data based on calcium shifts operated by different intracellular and extracellular mechanisms integrated with their cell phenotypes. From the classic synaptic structure to tripartite astrocytic model or the recent quadripartite microglia added ensemble, as well as other physiological tissues, it is possible to follow how cells signal spatiotemporally to cellular patterns. This methodology has been used broadly due to the universal properties of calcium as a second messenger. In general, at least two types of receptor operate through calcium permeation: a fast-acting ionotropic receptor channel and a slow-activating metabotropic receptor, added to exchangers/transporters/pumps and intracellular Ca 2+ release activated by messengers. These prototypes have gained an enormous amount of information in dynamic signaling circuits. SCCI has also been used as a method to associate phenotypic markers during development and stage transitions in progenitors, stem, vascular cells, neuro- and glioblasts, neurons, astrocytes, oligodendrocytes, and microglia that operate through ion channels, transporters, and receptors. Also, cancer cells or inducible cell lines from human organoids characterized by transition stages are currently being used to model diseases or reconfigure healthy cells in terms of the expression of calcium-binding/permeable molecules and shed light on therapy.

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Antihyperalgesic effect of CB1 receptor activation involves the modulation of P2X3 receptor in the primary afferent neuron

Cited by 28 publications

References 48 publications

Role of Nociceptor Toll-like Receptor 4 (TLR4) in Opioid-Induced Hyperalgesia and Hyperalgesic Priming

Role of Nociceptor Toll-like Receptor 4 (TLR4) in Opioid-Induced Hyperalgesia and Hyperalgesic Priming

Role of GPCR (mu-opioid)–receptor tyrosine kinase (epidermal growth factor) crosstalk in opioid-induced hyperalgesic priming (type II)

Cell Calcium Imaging as a Reliable Method to Study Neuron–Glial Circuits

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