Galectin-3 Inhibition Is Associated with Neuropathic Pain Attenuation after Peripheral Nerve Injury

PLoS One. 2016 Feb 12;11(2):e0148792. doi: 10.1371/journal.pone.0148792. eCollection 2016.


Neuropathic pain remains a prevalent and persistent clinical problem because it is often poorly responsive to the currently used analgesics. It is very urgent to develop novel drugs to alleviate neuropathic pain. Galectin-3 (gal3) is a multifunctional protein belonging to the carbohydrate-ligand lectin family, which is expressed by different cells. Emerging studies showed that gal3 elicits a pro-inflammatory response by recruiting and activating lymphocytes, macrophages and microglia. In the study we investigated whether gal3 inhibition could suppress neuroinflammation and alleviate neuropathic pain following peripheral nerve injury. We found that L5 spinal nerve ligation (SNL) increases the expression of gal3 in dorsal root ganglions at the mRNA and protein level. Intrathecal administration of modified citrus pectin (MCP), a gal3 inhibitor, reduces gal3 expression in dorsal root ganglions. MCP treatment also inhibits SNL-induced gal3 expression in primary rat microglia. SNL results in an increased activation of autophagy that contributes to microglial activation and subsequent inflammatory response. Intrathecal administration of MCP significantly suppresses SNL-induced autophagy activation. MCP also inhibits lipopolysaccharide (LPS)-induced autophagy in cultured microglia in vitro. MCP further decreases LPS-induced expression of proinflammatory mediators including IL-1β, TNF-α and IL-6 by regulating autophagy. Intrathecal administration of MCP results in adecreased mechanical and cold hypersensitivity following SNL. These results demonstrated that gal3 inhibition is associated with the suppression of SNL-induced inflammatory process andneurophathic pain attenuation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Autophagy
  • Cells, Cultured
  • Drug Evaluation, Preclinical
  • Galectin 3 / antagonists & inhibitors*
  • Galectin 3 / metabolism
  • Ganglia, Spinal / drug effects
  • Ganglia, Spinal / metabolism
  • Ganglia, Spinal / pathology
  • Hyperalgesia / drug therapy
  • Lipopolysaccharides / pharmacology
  • Male
  • Microglia / drug effects
  • Microglia / immunology
  • Microglia / metabolism
  • Neuralgia / drug therapy*
  • Pectins / pharmacology*
  • Peripheral Nerve Injuries / drug therapy*
  • Peripheral Nerve Injuries / immunology
  • Peripheral Nerve Injuries / physiopathology
  • Rats, Sprague-Dawley


  • Anti-Inflammatory Agents
  • Galectin 3
  • Lipopolysaccharides
  • citrus pectin
  • Pectins

Grant support

This work was supported by the Shanghai Key Laboratory of Clinical Geriatric Medicine (13dz2260700). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.