A new model of sciatic inflammatory neuritis (SIN): induction of unilateral and bilateral mechanical allodynia following acute unilateral peri-sciatic immune activation in rats.
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 3h) produces low threshold mechanical allodynia in the absence of thermal hyperalgesia. Low (4 microg) doses of zymosan produce both territorial and extra-territorial allodynia restricted to the ipsilateral hindpaw. Higher (40-400 microg) 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.
Chacur
Marucia
M
Laboratory of Pathophysiology, Butantan Institute, Avenue Vital Brazil, 1500, 05503-900 Sao Paulo, SP, Brazil Department of Psychology and the Center for Neurosciences, University of Colorado at Boulder, Boulder, CO 80309-0345, USA Laboratory of Biomedical Science, North Shore University Hospital, 350 Community Drive, Manhasset, NY 11030, USA.
Milligan
Erin D
ED
Gazda
Lawrence S
LS
Armstrong
Charles
C
Wang
Haichao
H
Tracey
Kevin J
KJ
Maier
Steven F
SF
Watkins
Linda R
LR
D000208:Acute Disease; D000818:Animals; D002404:Catheterization; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D024243:HMGB1 Protein / Q000493:pharmacokinetics; D006930:Hyperalgesia / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D008198:Lymph Nodes / Q000033:anatomy & histology; D008297:Male; D009929:Organ Size; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology*; D012585:Sciatica / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000033:anatomy & histology; D015054:Zymosan / Q000493:pharmacokinetics
D024243:HMGB1 Protein; D015054:Zymosan