Modulation of spinal nociceptive transmission from nuclei tractus solitarii: A relay for effects of vagal afferent stimulation

Academic Article

Abstract

  • 1. The effects of electrical and chemical stimulation in the nucleus tractus solitarii (NTS) on spinal nociceptive transmission were examined in pentobarbital sodium-anesthetized, paralyzed rats. These studies also examined the role of the NTS as a relay for the effects of vagal afferent stimulation (VAS) on spinal nociceptive transmission. All 75 neurons studied were located in laminae I-VI in the L3-L5 spinal segments, with receptive fields on the glabrous skin of the plantar surface of the ispilateral hindpaw. The units responded to mechanical (low and/or high intensities) and thermal stimuli (42-52°C). 2. Electrical stimulation in the NTS either ipsilateral or contralateral to the spinal unit inhibited neuronal responses to noxious thermal stimuli. The magnitude of inhibition did not significantly differ as a function of either ipsilateral (15 units) or contralateral (12 units) NTS stimulation (NTSS) as indicated by extrapolated thresholds for inhibition of responses to heat, intensities to produce 50% inhibition of responses to heat, and the slope of recruitment lines for inhibition. Tracking experiments also revealed that stimulation in the area ventral to the NTS produced a greater magnitude of inhibition of these units than did NTSS. 3. NTSS significantly decreased the slope of the stimulus-response functions (SRFs) of dorsal horn units to graded thermal stimuli (42-52°C), whereas response threshold was unaffected by NTSS. The apparent latency of NTSS to produce inhibition of unit responses to heating of the hindpaw was determined to be 50 ± 10 ms (mean ± SE). 4. Microinjection of 50 nmol of glutamate into the NTS ipsilateral to the spinal unit also inhibited neuronal responses to thermal stimuli in 17/21 units; responses of 2/21 units were facilitated. Inhibition typically lasted 4-7 min and was shown to be dose-volume dependent. 5. The effects of VAS and NTSS on spinal nociceptive transmission were directly compared. The responses of 17 units to 50°C heating of the hindpaw were facilitated by low and inhibited by greater intensities of VAS (Biphasic units); the responses of 12 units were only inhibited by VAS (Inhib units); three were only facilitated (Facil units), and 2 were unaffected by VAS. In contrast, NTSS generally inhibited the same spinal units, although modest facilitation was produced by NTSS contralateral to the recording site. NTSS produced greater inhibition of the Biphasic units than did VAS, shown by a leftward shift of the recruitment line of inhibition and greater inhibition at the same intensity of electrical stimulation. There were no significant differences between NTSS- and VAS-produced inhibition of Inhib units. 6. Microinjection of the local anesthetic lidocaine (4% 0.5 μl) into the NTS significantly attenuated VAS-produced inhibition of unit responses to heat and abolished VAS-produced depressor effects. Unit responses were inhibited by VAS to a mean of 51% of control before lidocaine microinjection but were inhibited to only 70 and 83% after the sequential administration of lidocaine into the contralateral and then ipsilateral NTS, respectively. At 46 min after the last microinjection of lidocaine, VAS-produced inhibition of spinal units had recovered to 62% of control values. When the order of microinjection of lidocaine was reversed (i.e., ipsilateral-contralateral sequential administration), inhibition by VAS was reduced from 59% of control to 80 and 88% of control, respectively. Microinjection of normal saline (0.5 μl) into the NTS had no significant effect on VAS-produced inhibition. VAS-produced facilitation of unit responses to heat was eliminated after microinjection of lidocaine into the contralateral but not ipsilateral NTS. 7. Potent descending inhibition of spinal nociceptive transmission is produced by NTSS. The efficacy of stimulation was equal from ipsilateral and contralateral NTS. Similar inhibitory effects are obtained by activating cells in the NTS with microinjections of glutamate. The inhibitory effect of NTSS is comparable with that of VAS on Inhib neurons, and local anesthesia of the NTS significantly attenuates VAS-produced inhibition of spinal nociceptive transmission. It is likely, therefore, that the NTS mediates the purely inhibitory effects of VAS. In contrast, NTSS is more efficacious than VAS in producing inhibition of Biphasic units, suggesting that facilitation produced by VAS may mask inhibition and relay in the NTS ipsilateral to the vagus stimulated.
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    Author List

  • Ren K; Randich A; Gebhart GF
  • Start Page

  • 971
  • End Page

  • 986
  • Volume

  • 63
  • Issue

  • 5