The persistent release of HMGB1 contributes to tactile hyperalgesia in a rodent model of neuropathic pain

Polina Feldman, Michael R. Due, Matthew S. Ripsch, Rajesh Khanna, Fletcher White

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Background: High-mobility group box-1 protein (HMGB1) is a nuclear protein that regulates gene expression throughout the body. It can also become cytoplasmic and function as a neuromodulatory cytokine after tissue damage or injury. The manner in which HMGB1 influences the peripheral nervous system following nerve injury is unclear. The present study investigated the degree to which HMGB1 signaling contributes to the maintenance of neuropathic pain behavior in the rodent.Results: Redistribution of HMGB1 from the nucleus to the cytoplasm occurred in both sensory neurons derived from a tibial nerve injured (TNI) rat and in a sensory neuron-like cell line following exposure to a depolarizing stimulus. We also observe that exogenous administration of HMGB1 to acutely dissociated sensory neurons derived from naïve or TNI rodents elicit increased excitability. Furthermore systemic injection of glycyrrhizin (50 mg/kg; i.p.), a known inhibitor of HMGB1, reversed TNI-induced mechanical hyperalgesia at fourteen days and three months following nerve injury.Conclusions: We have identified that a persistent endogenous release of HMGB1 by sensory neurons may be a potent, physiologically relevant modulator of neuronal excitability. More importantly, the use of the anti-inflammatory compound and known inhibitor of HMGB1, glycyrrhizin, has the ability to diminish persistent pain behavior in a model of peripheral neuropathy, presumably through its ability to neutralize the cyotkine. The identification of HMGB1 as a potential therapeutic target may contribute to a better understanding of mechanisms associated with chronic pain syndromes.

Original languageEnglish
Article number180
JournalJournal of Neuroinflammation
Volume9
DOIs
StatePublished - Jul 23 2012

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HMGB1 Protein
Hyperalgesia
Neuralgia
Rodentia
Sensory Receptor Cells
Tibial Nerve
Glycyrrhizic Acid
Aptitude
Wounds and Injuries
Peripheral Nervous System
Peripheral Nervous System Diseases
Nuclear Proteins
Chronic Pain
Cytoplasm
Anti-Inflammatory Agents
Maintenance
Cytokines
Gene Expression
Pain
Cell Line

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology
  • Immunology
  • Neuroscience(all)

Cite this

The persistent release of HMGB1 contributes to tactile hyperalgesia in a rodent model of neuropathic pain. / Feldman, Polina; Due, Michael R.; Ripsch, Matthew S.; Khanna, Rajesh; White, Fletcher.

In: Journal of Neuroinflammation, Vol. 9, 180, 23.07.2012.

Research output: Contribution to journalArticle

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abstract = "Background: High-mobility group box-1 protein (HMGB1) is a nuclear protein that regulates gene expression throughout the body. It can also become cytoplasmic and function as a neuromodulatory cytokine after tissue damage or injury. The manner in which HMGB1 influences the peripheral nervous system following nerve injury is unclear. The present study investigated the degree to which HMGB1 signaling contributes to the maintenance of neuropathic pain behavior in the rodent.Results: Redistribution of HMGB1 from the nucleus to the cytoplasm occurred in both sensory neurons derived from a tibial nerve injured (TNI) rat and in a sensory neuron-like cell line following exposure to a depolarizing stimulus. We also observe that exogenous administration of HMGB1 to acutely dissociated sensory neurons derived from na{\"i}ve or TNI rodents elicit increased excitability. Furthermore systemic injection of glycyrrhizin (50 mg/kg; i.p.), a known inhibitor of HMGB1, reversed TNI-induced mechanical hyperalgesia at fourteen days and three months following nerve injury.Conclusions: We have identified that a persistent endogenous release of HMGB1 by sensory neurons may be a potent, physiologically relevant modulator of neuronal excitability. More importantly, the use of the anti-inflammatory compound and known inhibitor of HMGB1, glycyrrhizin, has the ability to diminish persistent pain behavior in a model of peripheral neuropathy, presumably through its ability to neutralize the cyotkine. The identification of HMGB1 as a potential therapeutic target may contribute to a better understanding of mechanisms associated with chronic pain syndromes.",
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