The Journal of Neurophysiology Vol. 78 No. 3 September 1997, pp. 1285-1292
Copyright ©1997 The American Physiological Society

Inhibition of Bradykinin-Induced Plasma Extravasation Produced by Noxious Cutaneous and Visceral Stimuli and Its Modulation by Vagal Activity

Frederick Jia-Pei Miao¹, Wilfrid Jänig⁴, Paul G. Green¹, and Jon D. Levine^{1, 2}

¹ Department of Medicine, ² Department of Anatomy, and ³ Department of Oral and Maxillofacial Surgery, Schools of Medicine and Dentistry, University of California at San Francisco, San Francisco, California 94143-0452; and ⁴ Physiologisches Institut, Christian-Albrechts-Universität zu Kiel, 24098 Kiel, Germany

Miao, Frederick Jia-Pei, Wilfrid Jänig, Paul G. Green, and Jon D. Levine. Inhibition of bradykinin-induced plasma extravasation produced by noxious cutaneous and visceral stimuli and its modulation by vagal activity. J. Neurophysiol. 78: 1285-1292, 1997. Intrathecally applied nicotine reduces bradykinin-induced plasma extravasation (BK-induced PE) in the rat knee joint. This depression is mediated by the hypothalamo-pituitary-adrenal (HPA) axis and is enhanced by interruption of impulse traffic in afferents of the abdominal vagus nerve. Like intrathecal nicotine, electrical stimulation of unmyelinated cutaneous fibers also depresses BK-induced PE, which is also dependent on an intact HPA axis. In this study, we investigated whether the inhibitory effect of intrathecal nicotine can be mimicked by noxious stimulation of skin and of viscera. Furthermore we determined whether this depression is potentiated after subdiaphragmatic vagotomy. Stimulation of visceral afferents in the peritoneum, by intraperitoneal capsaicin injection, dose-dependently decreased BK-induced PE. The capsaicin dose-response function was shifted by 1.5-2 orders of magnitude to the left after vagotomy. Stimulation of visceral afferents in the urinary bladder by capsaicin also dose-dependently reduced BK-induced PE, which similarly was potentiated after vagotomy. Transcutaneous stimulation of unmyelinated nociceptive afferents from the plantar skin of the paw depressed BK-induced PE. This depression had a threshold of ~0.25 Hz and was maximal at a stimulation frequency of ~1 Hz. After subdiaphragmatic vagotomy, the stimulus response function shifted to the left and the inhibition was significantly larger than in control, in the range of 0.125-1 Hz stimulation. These results show that noxious stimulation of skin and viscera depressed BK-induced PE and that such depression was potentiated after subdiaphragmatic vagotomy in a manner similar to that of intrathecally applied nicotine. Based on these observations, we hypothesize that intrathecal nicotine depresses BK-induced PE by exciting spinal nociceptive neurons or the central projections of nociceptive primary afferent neurons.

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