Quantitative neuropathology of a focal nerve injury causing hyperalgesia.
The chronic constriction injury (CCI) model of neuropathy in the rat produces hyperalgesia and allodynia in the sciatic distribution of one hindlimb. We previously described the pathology of the affected nerves at the light microscopic and electron microscopic levels and in this report quantify the morphological changes of the nerves. This analysis gives new insights into the pathophysiology and pain-related mechanisms in this model of human neuropathy. We observed that total fascicular area increased up to fourfold due to an initial massive increase in edema and, later, endoneurial cells. Intact myelinated nerve fibers were reduced from 75% of fascicular area to 29.7% on day 1 and to a minimum of less than 0.5% on day 14 when edema had resolved. The few surviving myelinated fibers were in the small to medium size range. Fiber size histograms revealed an increase in fiber size early on, corresponding to fiber swelling, and the later loss of large as well as small myelinated fibers. Unmyelinated nerve fibers dropped from 19.36/1,000 microns 2 to 6.08/1,000 microns 2 on day 5, and increased from there on. Sprouts were first visible on light micrographs on day 7, occupying 6.8% of fascicular area, while regenerating fibers that were undergoing myelination reached 42.6% of fascicular area by day 42. Macrophage numbers were maximal on day 14 and were still increased on day 42. These data support the hypothesis that the pathogenesis of the extended hyperalgesia following chronic constrictive nerve injury is temporally linked with Wallerian-like degeneration and macrophage activation.(ABSTRACT TRUNCATED AT 250 WORDS)
Sommer
C
C
Department of Anesthesiology, University of California, San Diego 92093-0629, USA.
Lalonde
A
A
Heckman
H M
HM
Rodriguez
M
M
Myers
R R
RR
D000818:Animals; D004487:Edema; D005260:Female; D006614:Hindlimb; D006930:Hyperalgesia / Q000473:pathology / Q000503:physiopathology*; D008854:Microscopy, Electron; D009410:Nerve Degeneration; D009412:Nerve Fibers / Q000473:pathology* / Q000648:ultrastructure; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000648:ultrastructure; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology* / Q000648:ultrastructure; D013997:Time Factors