The Journal of Neurophysiology Vol. 81 No. 3 March 1999, pp. 1379-1390
Copyright ©1999 by the American Physiological Society
Primary Afferent Fibers That Contribute to Increased Substance P
Receptor Internalization in the Spinal Cord After Injury
Brian J.
Allen,1
Jun
Li,1,2
Patrick M.
Menning,1
Scott D.
Rogers,1
Joseph
Ghilardi,1
Patrick W.
Mantyh,1,2,3,4 and
Donald A.
Simone1,2,3
1Department of Preventive Sciences,
2Department of Psychiatry, and
3Graduate Program in Neuroscience,
University of Minnesota, Minneapolis, 55455; and
4Molecular Neurobiology Laboratory, Veterans
Affairs Medical Center, Minneapolis, Minnesota 55417
Allen, Brian J.,
Jun Li,
Patrick M. Menning,
Scott D. Rogers,
Joseph Ghilardi,
Patrick W. Mantyh, and
Donald A. Simone.
Primary afferent fibers that contribute to increased substance P
receptor internalization in the spinal cord after injury. Upon
noxious stimulation, substance P (SP) is released from primary afferent
fibers into the spinal cord where it interacts with the SP receptor
(SPR). The SPR is located throughout the dorsal horn and undergoes
endocytosis after agonist binding, which provides a spatial image of
SPR-containing neurons that undergo agonist interaction. Under normal
conditions, SPR internalization occurs only in SPR+ cell bodies and
dendrites in the superficial dorsal horn after noxious stimulation.
After nerve transection and inflammation, SPR immunoreactivity
increases, and both noxious as well as nonnoxious stimulation produces
SPR internalization in the superficial and deep dorsal horn. We
investigated the primary afferent fibers that contribute to enhanced
SPR internalization in the spinal cord after nerve transection and
inflammation. Internalization evoked by electrical stimulation of the
sciatic nerve was examined in untreated animals, at 14 days after
sciatic nerve transection or sham surgery and at 3 days after hindpaw
inflammation. Electrical stimulation was delivered at intensities to
excite A
fibers only, A and A
fibers or A and C fibers as
determined by the compound action potential recorded from the tibial
nerve. Electrical stimuli were delivered at a constant rate of 10 Hz
for a duration of 5 min. Transection of the sciatic nerve and
inflammation produced a 33.7 and 32.5% increase in SPR and
immunoreactivity in lamina I, respectively. Under normal conditions,
stimulation of A or C fibers evoked internalization that was
confined to the superficial dorsal horn. After transection or
inflammation, there was a 20-24% increase in the proportion of SPR+
lamina I neurons that exhibited internalization evoked by stimulation
of A fibers. The proportion of lamina I SPR+ neurons that exhibited
internalization after stimulation of C-fibers was not altered by
transection or inflammation because this was nearly maximal under
normal conditions. Moreover, electrical stimulation sufficient to
excite C fibers evoked SPR internalization in 22% of SPR+ lamina III
neurons after nerve transection and in 32-36% of SPR+ neurons in
lamina III and IV after inflammation. Stimulation of A fibers alone
never evoked internalization in the superficial or deep dorsal horn.
These results indicate that activation of small-caliber afferent fibers contributes to the enhanced SPR internalization in the spinal cord
after nerve transection and inflammation and suggest that recruitment
of neurons that possess the SPR contributes to hyperalgesia.
