The role of peripheral adenosine receptors in glutamate-induced pain nociceptive behavior

Macedo-Júnior, Sérgio José; Nascimento, Francisney Pinto do; Luiz-Cerutti, Murilo; Santos, Adair Roberto Soares

doi:10.1007/s11302-021-09781-y

Cited by 15 publications

(12 citation statements)

References 55 publications

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“…Immunohistochemically, A 1 receptors are detected in peripheral sensory neurons and particularly densely in lamina II of the dorsal horn of the spinal cord [ 11 , 12 ]. Antinociception by A 1 receptor activation is considered to involve the inhibition of synaptic transmission through the elevation of K + conductance in spinal dorsal horn neurons [ 13 ] and by peripheral terminal inhibition and presynaptic inhibition at the central terminals of sensory nerve fibers to inhibit nociceptive signal transduction via the release of neurotransmitters in the spinal cord [ 14 ]. Activation of A 1 receptors may have circuit-specific regulatory effects because the selective modulation of excitatory synaptic transmission in the intermediolateral cell column has been observed [ 15 ].…”

Section: A 1 Receptorsmentioning

confidence: 99%

The Role of Microglial Purinergic Receptors in Pain Signaling

2022

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Pain is an essential modality of sensation in the body. Purinergic signaling plays an important role in nociceptive pain transmission, under both physiological and pathophysiological conditions, and is important for communication between both neuronal and non-neuronal cells. Microglia and astrocytes express a variety of purinergic effectors, and a variety of receptors play critical roles in the pathogenesis of neuropathic pain. In this review, we discuss our current knowledge of purinergic signaling and of the compounds that modulate purinergic transmission, with the aim of highlighting the importance of purinergic pathways as targets for the treatment of persistent pain.

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Section: A 1 Receptorsmentioning

confidence: 99%

The Role of Microglial Purinergic Receptors in Pain Signaling

2022

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“…The involvement of these ion channels could occur through adenosine A 1 or A 2 A receptor activation. Peripherally, the inosine antinociception is mediated only by adenosine A 1 receptors but not by A 2 A ( Macedo-Júnior et al, 2021 ).…”

Section: Inosine and Painmentioning

confidence: 99%

Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

Nascimento

Macedo-Júnior²,

Lapa-Costa

et al. 2021

Front. Neurosci.

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Since the 1970s, when ATP was identified as a co-transmitter in sympathetic and parasympathetic nerves, it and its active metabolite adenosine have been considered relevant signaling molecules in biological and pathological processes in the central nervous system (CNS). Meanwhile, inosine, a naturally occurring purine nucleoside formed by adenosine breakdown, was considered an inert adenosine metabolite and remained a neglected actor on the purinergic signaling scene in the CNS. However, this scenario began to change in the 1980s. In the last four decades, an extensive group of shreds of evidence has supported the importance of mediated effects by inosine in the CNS. Also, inosine was identified as a natural trigger of adenosine receptors. This evidence has shed light on the therapeutic potential of inosine on disease processes involved in neurological and psychiatric disorders. Here, we highlight the clinical and preclinical studies investigating the involvement of inosine in chronic pain, schizophrenia, epilepsy, depression, anxiety, and in neural regeneration and neurodegenerative diseases, such as Parkinson and Alzheimer. Thus, we hope that this review will strengthen the knowledge and stimulate more studies about the effects promoted by inosine in neurological and psychiatric disorders.

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“…For example, A1 adenosine receptor agonists including adenosine can reduce nociceptive responses when they are injected into the hindpaws of animals [22,23]. It has recently been reported that activation of peripheral adenosine A1 receptors signi cantly relieves glutamateinduced nociceptive behavior [24]. The contribution of peripheral A1 adenosine receptors to analgesia is further supported by the results the analgesic effects of acetaminophen and tramadol are blocked by local administration of selective A1 adenosine receptor antagonists [25,26].…”

Section: Introductionmentioning

confidence: 99%

A1 Adenosine Receptor Activation Inhibits P2X3 Receptor–Mediated ATP Currents in Rat Dorsal Root Ganglion Neurons

Hao

Qiao

et al. 2022

Mol Neurobiol

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Purinergic signaling is involved in multiple pain processes. P2X3 receptor is a key target in pain therapeutics, while A1 adenosine receptor signaling plays a role in analgesia. However, it remains unclear whether there is a link between them in pain. The present results showed that the A1 adenosine receptor agonist N 6 -cyclopentyladenosine (CPA) concentration-dependently suppressed P2X3 receptor-mediated and α,β-methylene-ATP (α,β-meATP)-evoked inward currents in rat dorsal root ganglion (DRG) neurons.CPA signi cantly decreased the maximal current response of α,β-meATP, as shown a downward shift of its concentration-response curve. The CPA-induced suppression was independent on the clampingvoltageof the membrane. Inhibition of ATP currents by CPA was completely prevented by the A1 adenosine receptor antagonist KW-3902, and disappeared after the intracellular dialysis of either the G i/oprotein inhibitor pertussis toxin, the adenylate cyclase activator forskolin, or the cAMP analog 8-Br-cAMP.Morover, CPA suppressed the membrane potential depolarization and action potential burst induced by α,β-meATP in DRG neurons. Finally, CPA relieved α,β-meATP-induced nociceptive behaviors in rats by activating peripheral A1 adenosine receptors in dose-dependent manner. These results indicated that CPA inhibited P2X3 receptor activity in rat primary sensory neurons by activating A1 adenosine receptors, G i/oproteins and intracellular cAMP signaling, revealing a novel peripheral mechanism underlying its analgesic effect.

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The role of peripheral adenosine receptors in glutamate-induced pain nociceptive behavior

Cited by 15 publications

References 55 publications

The Role of Microglial Purinergic Receptors in Pain Signaling

The Role of Microglial Purinergic Receptors in Pain Signaling

Inosine as a Tool to Understand and Treat Central Nervous System Disorders: A Neglected Actor?

A1 Adenosine Receptor Activation Inhibits P2X3 Receptor–Mediated ATP Currents in Rat Dorsal Root Ganglion Neurons

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