The Role of Microglial Purinergic Receptors in Pain Signaling

Tozaki‐Saitoh, Hidetoshi; Takeda, Hiroshi; Inoue, Kazuhide

doi:10.3390/molecules27061919

Cited by 14 publications

(3 citation statements)

References 138 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Much attention has been devoted to the response of microglia in the dorsal horn in relation to pain mechanisms. These studies were mentioned earlier while discussing microglia activation mechanisms and there are many recent and thorough reviews from some of the key primary authors [9,[282][283][284][285][286][287][288][289]. We will not discuss them further.…”

Section: Theories Behind Microgliosis Around the Central Branches Of ...mentioning

confidence: 99%

The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury

Pottorf

Rotterman

McCallum

et al. 2022

Cells

View full text Add to dashboard Cite

Peripheral nerve injuries induce a pronounced immune reaction within the spinal cord, largely governed by microglia activation in both the dorsal and ventral horns. The mechanisms of activation and response of microglia are diverse depending on the location within the spinal cord, type, severity, and proximity of injury, as well as the age and species of the organism. Thanks to recent advancements in neuro-immune research techniques, such as single-cell transcriptomics, novel genetic mouse models, and live imaging, a vast amount of literature has come to light regarding the mechanisms of microglial activation and alluding to the function of microgliosis around injured motoneurons and sensory afferents. Herein, we provide a comparative analysis of the dorsal and ventral horns in relation to mechanisms of microglia activation (CSF1, DAP12, CCR2, Fractalkine signaling, Toll-like receptors, and purinergic signaling), and functionality in neuroprotection, degeneration, regeneration, synaptic plasticity, and spinal circuit reorganization following peripheral nerve injury. This review aims to shed new light on unsettled controversies regarding the diversity of spinal microglial-neuronal interactions following injury.

show abstract

Section: Theories Behind Microgliosis Around the Central Branches Of ...mentioning

confidence: 99%

The Role of Microglia in Neuroinflammation of the Spinal Cord after Peripheral Nerve Injury

Pottorf

Rotterman

McCallum

et al. 2022

Cells

View full text Add to dashboard Cite

show abstract

“…P2X4 activation in spinal microglia results in pain hypersensitivity ( Inoue, 2017 ; Stokes et al, 2017 ; Tozaki-Saitoh et al, 2022 ).…”

Section: Clinically Available Drugsmentioning

confidence: 99%

“…P2Y metabotropic receptors are G-protein-coupled receptors that are stimulated by purine and pyrimidine nucleotides. P2Y1 and/or P2Y2 receptor activation modulates TRP channels by lowering their activation threshold and thus favoring nociception ( Tozaki-Saitoh et al, 2022 ).…”

Section: Clinically Available Drugsmentioning

confidence: 99%

Neuropathic pain: Mechanisms and therapeutic strategies

Petroianu

Aloum

Adem

2023

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The physiopathology and neurotransmission of pain are of an owe inspiring complexity. Our ability to satisfactorily suppress neuropathic or other forms of chronic pain is limited. The number of pharmacodynamically distinct and clinically available medications is low and the successes achieved modest. Pain Medicine practitioners are confronted with the ethical dichotomy imposed by Hippocrates: On one hand the mandate of primum non nocere, on the other hand, the promise of heavenly joys if successful divinum est opus sedare dolorem. We briefly summarize the concepts associated with nociceptive pain from nociceptive input (afferents from periphery), modulatory output [descending noradrenergic (NE) and serotoninergic (5-HT) fibers] to local control. The local control is comprised of the “inflammatory soup” at the site of pain origin and synaptic relay stations, with an ATP-rich environment promoting inflammation and nociception while an adenosine-rich environment having the opposite effect. Subsequently, we address the transition from nociceptor pain to neuropathic pain (independent of nociceptor activation) and the process of sensitization and pain chronification (transient pain progressing into persistent pain). Having sketched a model of pain perception and processing we attempt to identify the sites and modes of action of clinically available drugs used in chronic pain treatment, focusing on adjuvant (co-analgesic) medication.

show abstract