Bj. Allen et al., Primary afferent fibers that contribute to increased substance P receptor internalization in the spinal cord after injury, J NEUROPHYS, 81(3), 1999, pp. 1379-1390
Upon noxious stimulation, substance P (SP) is released from primary afferen
t fibers into the spinal cord where it interacts with the SP receptor (SPR)
. The SPR is located throughout the dorsal horn and undergoes endocytosis a
fter agonist binding, which provides a spatial image of SPR-containing neur
ons that undergo agonist interaction. Under normal conditions, SPR internal
ization occurs only in SPR+ cell bodies and dendrites in the superficial do
rsal horn after noxious stimulation. After nerve transection and inflammati
on, SPR immunoreactivity increases, and both noxious as well as nonnoxious
stimulation produces SPR internalization in the superficial and deep dorsal
hem. We investigated the primary afferent fibers that contribute to enhanc
ed SPR internalization in the spinal cord after nerve transection and infla
mmation. Internalization evoked by electrical stimulation of the sciatic ne
rve was examined in untreated animals, at 14 days after sciatic nerve trans
ection or sham surgery and at 3 days after hindpaw inflammation. Electrical
stimulation was delivered at intensities to excite A beta fibers only, A b
eta and A delta fibers or A and C fibers as determined by the compound acti
on potential recorded from the tibial nerve. Electrical stimuli were delive
red 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 a
nd immunoreactivity in lamina I, respectively. Under normal conditions, sti
mulation of A delta or C fibers evoked internalization that was confined to
the superficial dorsal hem. 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 delta 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 nea
rly maximal under normal conditions. Moreover, electrical stimulation suffi
cient to excite C fibers evoked SPR internalization in 22% of SPR+ lamina I
II neurons after nerve transection and in 32-36% of SPR+ neurons in lamina
III and IV after inflammation. Stimulation of A beta fibers alone never evo
ked internalization in the superficial or deep dorsal horn. These results i
ndicate that activation of small-caliber afferent fibers contributes to the
enhanced SPR internalization in the spinal cord after nerve transection an
d inflammation and suggest that recruitment of neurons that possess the SPR
contributes to hyperalgesia.