A new model of sciatic inflammatory neuritis (SIN):... : PAIN (original) (raw)

Research papers

A new model of sciatic inflammatory neuritis (SIN): induction of unilateral and bilateral mechanical allodynia following acute unilateral peri-sciatic immune activation in rats

Chacur, Maruciaa; Milligan, Erin D.b; Gazda, Lawrence S.b; Armstrong, Charlesb; Wang, Haichaoc; Tracey, Kevin J.c; Maier, Steven F.b; Watkins, Linda R.b,*

a_Laboratory of Pathophysiology, Butantan Institute, Avenue Vital Brazil, 1500, 05503-900 Sao Paulo, SP, Brazil_

b_Department of Psychology and the Center for Neurosciences, University of Colorado at Boulder, Boulder, CO 80309-0345, USA_

c_Laboratory of Biomedical Science, North Shore University Hospital, 350 Community Drive, Manhasset, NY 11030, USA_

*Corresponding author. Tel.: +1-303-492-7034; fax: +1-303-492-2967

E-mail: [email protected]

Submitted December 18, 2000; revised April 11, 2001; accepted May 21, 2001.

Abstract

Immune activation near healthy peripheral nerves may have a greater role in creating pathological pain than previously recognized. We have developed a new model of sciatic inflammatory neuritis to assess how such immune activation may influence somatosensory processing. The present series of experiments reveal that zymosan (yeast cell walls) acutely injected around the sciatic nerve of awake unrestrained rats rapidly (within 3 h) produces low threshold mechanical allodynia in the absence of thermal hyperalgesia. Low (4 μg) doses of zymosan produce both territorial and extra-territorial allodynia restricted to the ipsilateral hindpaw. Higher (40–400 μg) doses of zymosan again produce both territorial and extra-territorial allodynia. However, allodynia is now expressed both in the ipsilateral as well as contralateral hindpaws. Several lines of evidence are provided that the appearance of this contralateral (‘mirror’) allodynia reflects local actions of zymosan on the sciatic nerve rather than spread of this immune activator to the general circulation. Since many clinical neuropathies result from inflammation/infection of peripheral nerves rather than frank physical trauma, understanding how immune activation alters pain processing may suggest novel approaches to pain control.