A review of dorsal root ganglia and primary sensory neuron plasticity mediating inflammatory and chronic neuropathic pain

Jang, Kyeongran; Garraway, Sandra M.

doi:10.1016/j.ynpai.2024.100151

Cited by 12 publications

(2 citation statements)

References 398 publications

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“…Our understanding of the cellular, synaptic, and molecular mechanisms underlying the genesis of pathological pain primarily stems from various animal models designed to mimic different clinical conditions. Numerous studies have investigated animal models of neuropathic pain induced by nerve injury or chemotherapy [175][176][177], inflammatory pain induced by CFA or carrageenan [177,178], bone cancer pain [177][178][179], arthritic pain [177,180], postoperative pain [177,181], and visceral pain [177,182]. However, our comprehension of the signaling molecules governing the pathology induced by SLE in the context of chronic pain is still in its nascent stage.…”

Section: Conclusion Remarks and Prospectivesmentioning

confidence: 99%

Emerging Molecular and Synaptic Targets for the Management of Chronic Pain Caused by Systemic Lupus Erythematosus

Weng

2024

IJMS

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Patients with systemic lupus erythematosus (SLE) frequently experience chronic pain due to the limited effectiveness and safety profiles of current analgesics. Understanding the molecular and synaptic mechanisms underlying abnormal neuronal activation along the pain signaling pathway is essential for developing new analgesics to address SLE-induced chronic pain. Recent studies, including those conducted by our team and others using the SLE animal model (MRL/lpr lupus-prone mice), have unveiled heightened excitability in nociceptive primary sensory neurons within the dorsal root ganglia and increased glutamatergic synaptic activity in spinal dorsal horn neurons, contributing to the development of chronic pain in mice with SLE. Nociceptive primary sensory neurons in lupus animals exhibit elevated resting membrane potentials, and reduced thresholds and rheobases of action potentials. These changes coincide with the elevated production of TNFα and IL-1β, as well as increased ERK activity in the dorsal root ganglion, coupled with decreased AMPK activity in the same region. Dysregulated AMPK activity is linked to heightened excitability in nociceptive sensory neurons in lupus animals. Additionally, the increased glutamatergic synaptic activity in the spinal dorsal horn in lupus mice with chronic pain is characterized by enhanced presynaptic glutamate release and postsynaptic AMPA receptor activation, alongside the reduced activity of glial glutamate transporters. These alterations are caused by the elevated activities of IL-1β, IL-18, CSF-1, and thrombin, and reduced AMPK activities in the dorsal horn. Furthermore, the pharmacological activation of spinal GPR109A receptors in microglia in lupus mice suppresses chronic pain by inhibiting p38 MAPK activity and the production of both IL-1β and IL-18, as well as reducing glutamatergic synaptic activity in the spinal dorsal horn. These findings collectively unveil crucial signaling molecular and synaptic targets for modulating abnormal neuronal activation in both the periphery and spinal dorsal horn, offering insights into the development of analgesics for managing SLE-induced chronic pain.

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Section: Conclusion Remarks and Prospectivesmentioning

confidence: 99%

Emerging Molecular and Synaptic Targets for the Management of Chronic Pain Caused by Systemic Lupus Erythematosus

Weng

2024

IJMS

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“…Additionally, DRG neurons express numerous cytokines and chemokines and their receptors, underscoring the pivotal role of DRGs in nociception following tissue injury. 69 The TWIK‐related spinal cord K+ (TRESK), a factor in neuropathic pain response, constitutes the major background potassium current in DRGs. Following SCI, TRESK suppression occurs concomitantly with MAPK signaling pathway activation, a process mitigated by ERK antagonist (PD98059) and p38 antagonist (SB203580).…”

Section: Roles Of Mapk In the Treatment Of Scimentioning

confidence: 99%

Advances of the MAPK pathway in the treatment of spinal cord injury

Huang,

Zhang,

Shu

et al. 2024

CNS Neurosci Ther

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Spinal cord injury (SCI) represents a complex pathology within the central nervous system (CNS), leading to severe sensory and motor impairments. It activates various signaling pathways, notably the mitogen‐activated protein kinase (MAPK) pathway. Present treatment approaches primarily focus on symptomatic relief, lacking efficacy in addressing the underlying pathophysiological mechanisms. Emerging research underscores the significance of the MAPK pathway in neuronal differentiation, growth, survival, axonal regeneration, and inflammatory responses post‐SCI. Modulating this pathway post‐injury has shown promise in attenuating inflammation, minimizing apoptosis, alleviating neuropathic pain, and fostering neural regeneration. Given its pivotal role, the MAPK pathway emerges as a potential therapeutic target in SCI management. This review synthesizes current knowledge on SCI pathology, delineates the MAPK pathway's characteristics, and explores its dual roles in SCI pathology and therapeutic interventions. Furthermore, it addresses the existing challenges in MAPK research in the context of SCI, proposing solutions to overcome these hurdles. Our aim is to offer a comprehensive reference for future research on the MAPK pathway and SCI, laying the groundwork for targeted therapeutic strategies.

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