Synchronized cluster firing, a distinct form of sensory neuron activation, drives spontaneous pain

Qin, Zheng; Xie, Wenrui; Lückemeyer, Débora Denardin; Lay, Mark C.; Wang, Xue-Wei; Dong, Xintong; Limjunyawong, Nathachit; Ye, Yaqing; Zhou, Feng‐Quan; Strong, Judith A.; Zhang, Junming; Dong, Xinzhong

doi:10.1016/j.neuron.2021.10.019

Cited by 58 publications

(45 citation statements)

References 58 publications

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“…In addition, Zhang et al 60 discovered a unique form of abnormal spontaneous activity following peripheral nerve injury: synchronous and sporadic firing of adjacent clusters of DRG neurons. Furthermore, they demonstrated that cluster firing is triggered by sympathetic activity and identified NE as a key neurotransmitter regulating this unique firing 60 . As one of the important sympathetic ganglions, SGI intervention may relieve pain associated with sympathetic maintenance by inhibiting sprouting and new nerve growth through sympathetic modulation.…”

Section: Analgesic Mechanisms Of Sgimentioning

confidence: 99%

“…59 Besides, these neurons can be repeatedly activated by sympathetic stimulation. 59 In addition, Zhang et al 60 discovered a unique form of abnormal spontaneous activity following peripheral nerve injury: synchronous and sporadic firing of adjacent clusters of DRG neurons. Furthermore, they demonstrated that cluster firing is triggered by sympathetic activity and identified NE as a key neurotransmitter F I G U R E 1 Methods and indications of stellate ganglion intervention (SGI).…”

Section: Analgesic Mechanisms Of Sgimentioning

confidence: 99%

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Stellate ganglion intervention for chronic pain: A review

Luo

Wen

Tan

et al. 2022

Ibrain

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Stellate ganglion (SG) intervention is currently widely being studied in many kinds of chronic pain. As one of the convenient ways to treat the sympathetic nervous system, the indications for stellate ganglion intervention (SGI) include complex regional pain syndrome, postherpetic neuralgia, cancer pain of different origins, orofacial pain, and so forth. SGI refers to the reversible or irreversible blocking of the cervical sympathetic trunk, cervical sympathetic ganglion, and their innervation range through noninvasive or minimally invasive treatment. Current treatment options include stellate ganglion block (SGB), SG pulsed radiofrequency, continuous radiofrequency treatment, and noninvasive SGB. In particular, SGB continues to be one of the most studied methods in chronic pain management. However, a single SGB usually provides only short-term effects; repeated SGB may result in complications such as hoarseness, light-headedness, and vessel or nerve injury. Meanwhile, the mechanism of SGI is still unclear. This review discusses the research progress of SGI methods, effectiveness, complications, and possible mechanisms in the management of chronic pain.chronic pain, pulse radiofrequency, stellate ganglion, stellate ganglion block | INTRODUCTIONChronic pain is defined as pain that persists or recurs for more than 3 months, usually accompanied by negative emotions including anxiety and/or depression. 1 Chronic pain severely affects not only physical and mental health but also places a huge economic burden on the family and society. The incidence of chronic pain is reported to be over 30% in China. 2 Current conventional methods for the treatment of chronic pain include drug therapy, minimally invasive therapy, psychotherapy, and physical therapy. 3 However, research has found that sympathetic nerves are involved in the maintenance of many kinds of chronic pain. 4 Therefore, inhibition of sympathetic hyperexcitability may improve the therapeutic effect, which may be related to the involvement of sympathetic nerves in regulating glial inflammation. 5 Among them, intervention of stellate ganglion (SG) is effective for pain in the head, face, neck, upper limbs, or upper chest. In this review, we summarize the clinical evidence available for the effectiveness of stellate ganglion intervention (SGI), and demonstrate clinical applications of SGI.

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Section: Analgesic Mechanisms Of Sgimentioning

confidence: 99%

Section: Analgesic Mechanisms Of Sgimentioning

confidence: 99%

Stellate ganglion intervention for chronic pain: A review

Luo

Wen

Tan

et al. 2022

Ibrain

View full text Add to dashboard Cite

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“…However, our present study has some limitations. There are distinct etiologies in different forms of neuropathic pain (68)(69)(70)(71). It is still unclear whether up-regulation of GPR177/WNT5a and enhancement of WNT5a secretion could be induced by other neuropathic pain states such as peripheral nerve injury.…”

Section: Discussionmentioning

confidence: 99%

GPR177 in A-fiber sensory neurons drives diabetic neuropathic pain via WNT-mediated TRPV1 activation

et al. 2022

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Diabetic neuropathic pain (DNP) is a common and devastating complication in patients with diabetes. The mechanisms mediating DNP are not completely elucidated, and effective treatments are lacking. A-fiber sensory neurons have been shown to mediate the development of mechanical allodynia in neuropathic pain, yet the molecular basis underlying the contribution of A-fiber neurons is still unclear. Here, we report that the orphan G protein–coupled receptor 177 (GPR177) in A-fiber neurons drives DNP via WNT5a-mediated activation of transient receptor potential vanilloid receptor-1 (TRPV1) ion channel. GPR177 is mainly expressed in large-diameter A-fiber dorsal root ganglion (DRG) neurons and required for the development of DNP in mice. Mechanistically, we found that GPR177 mediated the secretion of WNT5a from A-fiber DRG neurons into cerebrospinal fluid (CSF), which was necessary for the maintenance of DNP. Extracellular perfusion of WNT5a induced rapid currents in both TRPV1-expressing heterologous cells and nociceptive DRG neurons. Computer simulations revealed that WNT5a has the potential to bind the residues at the extracellular S5-S6 loop of TRPV1. Using a peptide able to disrupt the predicted WNT5a/TRPV1 interaction suppressed DNP- and WNT5a-induced neuropathic pain symptoms in rodents. We confirmed GPR177/WNT5A coexpression in human DRG neurons and WNT5A secretion in CSF from patients with DNP. Thus, our results reveal a role for WNT5a as an endogenous and potent TRPV1 agonist, and the GPR177-WNT5a-TRPV1 axis as a driver of DNP pathogenesis in rodents. Our findings identified a potential analgesic target that might relieve neuropathic pain in patients with diabetes.

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“…After peripheral nerve injury, sympathetic neurons sprout within DRG, sensitizing nociceptive neurons to adrenergic stimulation, although this remains controversial ( Hoffman et al, 2018 ). A new study provided evidence that sympathetic sprouting in the DRG played a role in spontaneous pain in the SNI and related neuropathic pain models ( Zheng et al, 2022 ). They concluded that norepinephrine released from sympathetic induced DRG neuronal clustering discharge, which correlated directly with spontaneous pain behavior caused by nerve injury.…”

Section: Discussionmentioning

confidence: 99%

Potential mechanisms of acupuncture for neuropathic pain based on somatosensory system

Chen

Yang

et al. 2022

Front. Neurosci.

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Neuropathic pain, caused by a lesion or disease of the somatosensory system, is common and distressing. In view of the high human and economic burden, more effective treatment strategies were urgently needed. Acupuncture has been increasingly used as an adjuvant or complementary therapy for neuropathic pain. Although the therapeutic effects of acupuncture have been demonstrated in various high-quality randomized controlled trials, there is significant heterogeneity in the underlying mechanisms. This review aimed to summarize the potential mechanisms of acupuncture on neuropathic pain based on the somatosensory system, and guided for future both foundational and clinical studies. Here, we argued that acupuncture may have the potential to inhibit neuronal activity caused by neuropathic pain, through reducing the activation of pain-related ion channels and suppressing glial cells (including microglia and astrocytes) to release inflammatory cytokines, chemokines, amongst others. Meanwhile, acupuncture as a non-pharmacologic treatment, may have potential to activate descending pain control system via increasing the level of spinal or brain 5-hydroxytryptamine (5-HT), norepinephrine (NE), and opioid peptides. And the types of endogenously opioid peptides was influenced by electroacupuncture-frequency. The cumulative evidence demonstrated that acupuncture provided an alternative or adjunctive therapy for neuropathic pain.

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Synchronized cluster firing, a distinct form of sensory neuron activation, drives spontaneous pain

Cited by 58 publications

References 58 publications

Stellate ganglion intervention for chronic pain: A review

Stellate ganglion intervention for chronic pain: A review

GPR177 in A-fiber sensory neurons drives diabetic neuropathic pain via WNT-mediated TRPV1 activation

Potential mechanisms of acupuncture for neuropathic pain based on somatosensory system

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