The effect of IL-6/Piezo2 on the trigeminal neuropathic pain

Liu, MingXing; Li, Yan; Zhong, Jun; Xia, Lei; Dou, Ning-Ning

doi:10.18632/aging.202887

Cited by 23 publications

(20 citation statements)

References 31 publications

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“…These observations indicate that LP2 effect on MOR or DOR is sufficient to modulate TNF signalling. In contrast, targeting DOR is required to modulate IL-6 increase mediated by neuropathy in the late phase, confirming a critical role of IL-6 in inducing neuropathy chronicization and maintenance [ 41 , 42 ].…”

Section: Discussionmentioning

confidence: 95%

Mu and Delta Opioid Receptor Targeting Reduces Connexin 43-Based Heterocellular Coupling during Neuropathic Pain

Vicario

Denaro

Turnaturi

et al. 2022

IJMS

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Chronic neuropathic pain emerges from either central or peripheral lesions inducing spontaneous or amplified responses to non-noxious stimuli. Despite different pharmacological approaches to treat such a chronic disease, neuropathic pain still represents an unmet clinical need, due to long-term therapeutic regimens and severe side effects that limit application of currently available drugs. A critical phenomenon involved in central sensitization is the exchange of signalling molecules and cytokines, between glia and neurons, driving the chronicization process. Herein, using a chronic constriction injury (CCI) model of neuropathic pain, we evaluated the efficacy of the mu (M-) and delta (D-) opioid receptor (-OR) targeting agent LP2 in modulating connexin-based heterocellular coupling and cytokine levels. We found that long-term efficacy of LP2 is consequent to MOR-DOR targeting resulting in the reduction of CCI-induced astrocyte-to-microglia heterocellular coupling mediated by connexin 43. We also found that single targeting of DOR reduces TNF and IL-6 levels in the chronic phase of the disease, but the peripheral and central discharge as the primary source of excitotoxic stimulation in the spinal cord requires a simultaneous MOR-DOR targeting to reduce CCI-induced neuropathic pain.

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Section: Discussionmentioning

confidence: 95%

Mu and Delta Opioid Receptor Targeting Reduces Connexin 43-Based Heterocellular Coupling during Neuropathic Pain

Vicario

Denaro

Turnaturi

et al. 2022

IJMS

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“…Piezo2 has a similar structure to Piezo1 as well as mechanosensitivity ( 171 ). Piezo2 is expressed on and exerts mechanotransduction in various mechanosensitive tissues and is associated with various inflammatory diseases ( 172 – 174 ). Human Piezo2 defects and Piezo2 gain-of-function mutations are associated with respiratory insufficiency at birth, chronic obstructive pulmonary disease, and adult sleep apnea ( 175 – 177 ).…”

Section: Conclusion and Future Research Directionsmentioning

confidence: 99%

Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation

Liu

Zheng

et al. 2022

Front. Immunol.

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Mechanical damage is one of the predisposing factors of inflammation, and it runs through the entire inflammatory pathological process. Repeated or persistent damaging mechanical irritation leads to chronic inflammatory diseases. The mechanism of how mechanical forces induce inflammation is not fully understood. Piezo1 is a newly discovered mechanically sensitive ion channel. The Piezo1 channel opens in response to mechanical stimuli, transducing mechanical signals into an inflammatory cascade in the cell leading to tissue inflammation. A large amount of evidence shows that Piezo1 plays a vital role in the occurrence and progression of chronic inflammatory diseases. This mini-review briefly presents new evidence that Piezo1 responds to different mechanical stresses to trigger inflammation in various tissues. The discovery of Piezo1 provides new insights for the treatment of chronic inflammatory diseases related to mechanical stress. Inhibiting the transduction of damaging mechanical signals into inflammatory signals can inhibit inflammation and improve the outcome of inflammation at an early stage. The pharmacology of Piezo1 has shown bright prospects. The development of tissue-specific Piezo1 drugs for clinical use may be a new target for treating chronic inflammation.

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“…Sonkodi et al attributed this effect to the heat shock protein 70 (Hsp70) activated Toll-like receptor 4 (TLR4)/IL-6 (IL-6)/tumor necrosis factor alpha (TNF-α) pathway, based on the work of Dos Santos et al [ 112 , 113 ]. The upregulation of Piezo2 and IL-6 seems to be paralleled in the dorsal root ganglion (DRG) of chronic neural constriction injury [ 114 ]. The author translates this phenomenon as one consequence of the chronic Piezo2 channelopathy being this upregulation and ganglionopathy.…”

Section: Quad-phasic Non-contact Injury Modelmentioning

confidence: 99%

Psoriasis, Is It a Microdamage of Our “Sixth Sense”? A Neurocentric View

Sonkodi

2022

IJMS

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Psoriasis is considered a multifactorial and heterogeneous systemic disease with many underlying pathologic mechanisms having been elucidated; however, the pathomechanism is far from entirely known. This opinion article will demonstrate the potential relevance of the somatosensory Piezo2 microinjury-induced quad-phasic non-contact injury model in psoriasis through a multidisciplinary approach. The primary injury is suggested to be on the Piezo2-containing somatosensory afferent terminals in the Merkel cell–neurite complex, with the concomitant impairment of glutamate vesicular release machinery in Merkel cells. Part of the theory is that the Merkel cell–neurite complex contributes to proprioception; hence, to the stretch of the skin. Piezo2 channelopathy could result in the imbalanced control of Piezo1 on keratinocytes in a clustered manner, leading to dysregulated keratinocyte proliferation and differentiation. Furthermore, the author proposes the role of mtHsp70 leakage from damaged mitochondria through somatosensory terminals in the initiation of autoimmune and autoinflammatory processes in psoriasis. The secondary phase is harsher epidermal tissue damage due to the primary impaired proprioception. The third injury phase refers to re-injury and sensitization with the derailment of healing to a state when part of the wound healing is permanently kept alive due to genetical predisposition and environmental risk factors. Finally, the quadric damage phase is associated with the aging process and associated inflammaging. In summary, this opinion piece postulates that the primary microinjury of our “sixth sense”, or the Piezo2 channelopathy of the somatosensory terminals contributing to proprioception, could be the principal gateway to pathology due to the encroachment of our preprogrammed genetic encoding.

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The effect of IL-6/Piezo2 on the trigeminal neuropathic pain

Cited by 23 publications

References 31 publications

Mu and Delta Opioid Receptor Targeting Reduces Connexin 43-Based Heterocellular Coupling during Neuropathic Pain

Mu and Delta Opioid Receptor Targeting Reduces Connexin 43-Based Heterocellular Coupling during Neuropathic Pain

Piezo1 Channels as Force Sensors in Mechanical Force-Related Chronic Inflammation

Psoriasis, Is It a Microdamage of Our “Sixth Sense”? A Neurocentric View

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