Fjp. Miao et al., ROLE OF VAGAL AFFERENTS AND SPINAL PATHWAYS MODULATING INHIBITION OF BRADYKININ-INDUCED PLASMA EXTRAVASATION TRY INTRATHECAL NICOTINE, Journal of neurophysiology, 72(3), 1994, pp. 1199-1207
1. Nicotine, a major active component of tobacco smoke, has been shown
to modulate the inflammatory response via both peripheral and central
nervous system pathways. Recently we found that spinal intrathecal ad
ministration of nicotine dose-dependently inhibits bradykinin-induced
plasma extravasation (BK-induced PE) in the knee joint of the rat and
that the dose-response curve for the inhibition of BK-induced PE by in
trathecal nicotine is shifted to the left, by six orders of magnitude,
after surgical interventions in the abdominal cavity, which might hav
e interrupted visceral afferents to the neuraxis. Therefore we focused
, in this study, on the contribution of the vagal afferents to depress
ion of BK-induced PE by intrathecal nicotine. Furthermore, the effect
of acute spinalization at the level C-6-C-8 was investigated. The hypo
thesis was that impulse activity in vagal afferents has a pronounced i
nhibitory effect on the modulation of BK-induced PE by intrathecal nic
otine and that spinal pathways are important in mediating this effect.
2. Chronic subdiaphragmatic vagotomy and elimination of vagal afferen
ts, by neonatal capsaicin treatment or by application of kainic acid t
o the nodose ganglia, enhanced the potency of intrathecal nicotine dep
ression of BK-induced PE, by six to seven orders of magnitude when com
pared with the control. 3. Acute subdiaphragmatic vagotomy enhanced th
e potency of intrathecal nicotine-induced depression of BK-induced PE
(without changing its maximum effect), by about three to four orders o
f magnitude when compared with the sham-operated (control) animals wit
h intact vagus nerves). 4. Electrical stimulation of the central stump
of the crushed subdiaphragmatic vagus nerve reduced the potency of in
trathecal nicotine, which reversed the enhancing effects of the origin
al crush injury. 5. Acute spinalization, at the level of C-6-C-8, near
ly abolished the depression of BK-induced PE generated by intrathecal
nicotine. 6. These results strongly favor the view that activity in va
gal afferents from abdominal viscera regulate the suppression of BK-in
duced PE that is generated by intrathecal infusion of nicotine. The in
teraction may occur in the spinal cord or in the brain stem. Identific
ation of the mechanism by which the signal gets from the CNS to the si
te of plasma extravasation awaits further study.