Tags

Type your tag names separated by a space and hit enter

Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury.
Brain Behav Immun. 2007 Feb; 21(2):238-46.BB

Abstract

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.

Authors+Show Affiliations

Department of Pharmacology, Dartmouth Medical School, Hanover, NH 03755, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16949251

Citation

Tawfik, Vivianne L., et al. "Efficacy of Propentofylline, a Glial Modulating Agent, On Existing Mechanical Allodynia Following Peripheral Nerve Injury." Brain, Behavior, and Immunity, vol. 21, no. 2, 2007, pp. 238-46.
Tawfik VL, Nutile-McMenemy N, Lacroix-Fralish ML, et al. Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury. Brain Behav Immun. 2007;21(2):238-46.
Tawfik, V. L., Nutile-McMenemy, N., Lacroix-Fralish, M. L., & Deleo, J. A. (2007). Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury. Brain, Behavior, and Immunity, 21(2), 238-46.
Tawfik VL, et al. Efficacy of Propentofylline, a Glial Modulating Agent, On Existing Mechanical Allodynia Following Peripheral Nerve Injury. Brain Behav Immun. 2007;21(2):238-46. PubMed PMID: 16949251.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy of propentofylline, a glial modulating agent, on existing mechanical allodynia following peripheral nerve injury. AU - Tawfik,Vivianne L, AU - Nutile-McMenemy,Nancy, AU - Lacroix-Fralish,Michael L, AU - Deleo,Joyce A, Y1 - 2006/09/01/ PY - 2006/06/21/received PY - 2006/07/06/revised PY - 2006/07/07/accepted PY - 2006/9/5/pubmed PY - 2007/3/3/medline PY - 2006/9/5/entrez SP - 238 EP - 46 JF - Brain, behavior, and immunity JO - Brain Behav Immun VL - 21 IS - 2 N2 - 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. SN - 0889-1591 UR - https://www.unboundmedicine.com/medline/citation/16949251/Efficacy_of_propentofylline_a_glial_modulating_agent_on_existing_mechanical_allodynia_following_peripheral_nerve_injury_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0889-1591(06)00258-3 DB - PRIME DP - Unbound Medicine ER -