[Abstract Title]. - Society for Neuroscience

Title: Expression of c-Fos in a rodent model of central pain syndrome reveals the anatomical
loci of altered pain sensation
Authors: *G. WANG, S. M. THOMSON;
Dept Physiol, Med. Sch. UMB, Baltimore, MD
Abstract: Central pain syndrome (CPS) is defined as pain associated with a lesion of the central
nervous system and is a common consequence of spinal cord injuries. CPS patients experienced
severe, excruciating pain, either spontaneously or in response to non-noxious stimulation, and
are highly resistant to opioid analgesia. The mechanisms underlying the genesis of CPS remain
unclear. We have generated a rodent model of CPS by making unilateral electrolytic lesions
centered on the spinothalamic tract in rats (T8-T9). We observe thermal hyperalgesia and
mechanical allodynia bilaterally in both hind and forepaws beginning 7 days postlesion and
persisting for >31 days postlesion. We also observe an increased probability of burst responses in
the ventral posterior lateral nucleus (VPL), a postsynaptic target of the lesioned spinothalamic
tract axons, in thalamic brain slices after lesion. Both bursting and altered pain sensation are
eliminated by the T-type calcium channel blocker ethosuximide.
In the present study, we used the immunocytochemical detection of the immediate early gene, c-
Fos, to map brain regions displaying pathologically elevated activity levels. We compared c-Fos
expression patterns in brain sections from rats with spinothalamic tract lesions to the pattern of c-
Fos expression induced acutely as a consequence of hind paw inflammation produced by
injection of Complete Freunds Adjuvant. c-Fos expression was negligible in sham control
animals. In CPS animals, in contrast, high levels of nuclear c-Fos expression were observed in
the anterior cingular cortex, somatosensory cortex, thalamic midline nuclei, posterior regions of
the VPL, the tegmentum, and dorsal part of periaqueductal gray. The distribution pattern of c-
Fos expression in CPS animals was similar as that induced by acute hind paw inflammation. In
CPS rats, c-Fos expressing cells were not co-labeled with antibodies against either enkephalin or
GABA.
The pathological bursting activity of VPL neurons and the ability of ethosuximide to block this
bursting and relieve pain behaviors indicates a primary role for the somatosensory thalamic
nuclei in CPS. The widespread pattern of elevated c-Fos expression, however, suggests that the
changes of pain behaviors induced by spinothalamic tract lesion are also accompanied by plastic
changes in many pain related brain regions.
Disclosures: G. Wang , None; S.M. Thomson, None.
Poster
267. Pain: Pain Models II
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 267.8/FF14