E. Pertens et al., Intraspinal and behavioral consequences of nerve growth factor-induced nociceptive sprouting and nerve growth factor-induced hyperalgesia compared inadult rats, J COMP NEUR, 410(1), 1999, pp. 73-89
Intraspinal and behavioral events were studied in adult rats with nocicepti
ve nerves that were undergoing collateral sprouting into adjacent denervate
d skin. This sprouting, which is driven by endogenous nerve growth factor (
NGF), did not cause hyperalgesia. For comparison, we studied an exogenous N
GF administration that induced hyperalgesia but was too brief to evoke spro
uting. When nociceptive nerves sprouted in skin, back-labeling with wheat g
erm agglutinin-conjugated horseradish peroxidase revealed that their projec
tions sprouted in the cord. The sprouted peripheral nerves now activated mo
re c-Fos-containing interneurons, which stimulus-response studies showed wa
s not due to an increased afferent discharge. We attribute the interneuron
recruitment to synaptogenesis following the intraspinal sprouting. Nocicept
ive stimulation of dorsal skin reflexly activates underlying cutaneous trun
ci muscle (CTM). When a nociceptive field expanded by nerve sprouting, so d
id the area of the evoked CTM reflex: this implies a recruitment of CTM mot
oneurons. We interpret this "matching" of response to stimulus as an adapti
ve phenomenon ensured by an adaptive intraspinal sprouting of the nocicepti
ve projections. Neither the intraspinal changes nor the reflex changes occu
rred if peripheral sprouting was blocked by systemic anti-NGF treatment, in
dicating that the role of endogenous NGF was only in that sprouting. No com
parable adaptive events occurred during NGF-induced hyperalgesia. Neither n
ociceptive fields nor CTM reflexes were affected; however there was a recru
itment of c-Fos-expressing interneurons. This recruitment was not explained
by peripheral sensitization, and, because sprouting was not involved here,
we attribute the recruitment to "synaptic unmasking," i.e., an increased e
ffectiveness of the preexisting excitatory circuitry. (C) 1999 Wiley-Liss,
Inc.