Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury.

Increasing evidence points to a role for spinal neuroimmune dysregulation (glial cell activation and cytokine expression) in the pathogenesis of chronic pain. Suppression of astrocytic and microglial activation with the methylxanthine derivative, propentofylline, pre-emptively attenuates the development of nerve injury-induced allodynia. Currently, we investigated the ability of systemic propentofylline to reverse existing, long-term allodynia after nerve injury--a clinically relevant paradigm. Rats received L5 spinal nerve transection or sham surgery and the development of mechanical allodynia was assessed daily for 2 weeks, at which time injured rats exhibited robust responses to non-noxious von Frey filaments. On days 14-27, rats received either saline or 101 mg/kg propentofylline by intraperitoneal (i.p.) injection. On day 28 or 42 (after a 14-day drug washout period), lumbar spinal cord sections were processed for assessment of astrocytic glial fibrillary acidic protein (GFAP) and microglial OX-42 (antibody against CR3/CD11b). Propentofylline treatment to nerve injured rats resulted in significant reversal of allodynia that lasted throughout the 14-day washout period. Spinal microglial activation was observed at days 28 and 42 post-injury at the protein level, in the absence of mRNA level changes. Less robust increases in GFAP immunoreactivity were observed at days 28 and 42 post-transection. Interestingly, propentofylline treatment suppressed microglial activation at both time points in this paradigm. Taken together, our results highlight the clinical potential of the glial modulating agent, propentofylline, for the treatment of neuropathic pain as well as a role for microglia in the long-term maintenance of allodynia.
AuthorsVivianne L Tawfik, Nancy Nutile-McMenemy, Michael L Lacroix-Fralish, Joyce A Deleo
JournalBrain, behavior, and immunity (Brain Behav Immun) Vol. 21 Issue 2 Pg. 238-46 (Feb 2007) ISSN: 0889-1591 [Print] United States
PMID16949251 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD11b
  • Glial Fibrillary Acidic Protein
  • Macrophage-1 Antigen
  • Neuroprotective Agents
  • RNA, Messenger
  • Xanthines
  • propentofylline
  • Animals
  • Antigens, CD11b (genetics, metabolism)
  • Glial Fibrillary Acidic Protein (genetics, metabolism)
  • Macrophage-1 Antigen (genetics, metabolism)
  • Male
  • Mechanoreceptors (drug effects, physiology)
  • Neuroglia (drug effects, metabolism)
  • Neuroprotective Agents (pharmacology)
  • Pain Threshold (drug effects, physiology)
  • Peripheral Nervous System Diseases (drug therapy, metabolism)
  • RNA, Messenger (analysis)
  • Rats
  • Rats, Sprague-Dawley
  • Spinal Cord (cytology, drug effects, metabolism)
  • Xanthines (pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: