Spino-bulbo-spinal pathway mediating vagal modulation of nociceptive-neuroendocrine control of inflammation in the rat

1. Stimulation of nociceptors by intradermal capsaicin produces depression of bradykinin (BK)-induced synovial plasma extravasation (PE) that is markedly enhanced by subdiaphragmatic vagotomy. This depression is mediated by the adrenal medullae, a propriospinal pathway between the afferent nociceptive input and preganglionic neurones projecting to the adrenal medullae, and a spino-bulbo-spinal pathway. Here we investigated the role of spinal ascending and descending pathways in the interaction between noxious and vagal afferent inputs, leading to inhibition of BK-induced PE mediated by the adrenal medullae. Nociceptors in the paw were activated by capsaicin and depression of BK-induced PE was measured in rats with intact or cut subdiaphragmatic vagus nerves. 2. After cutting the dorsolateral funiculus (DLF) contralateral to the stimulated hindpaw (segment;al level C-5/C-6 and T-8/T-9), depression of BK-induced PE was weak or absent both in rats with intact vagus nerves and in vagotomised rats, suggesting that an ascending excitatory pathway was interrupted. 3. After cutting the DLF ipsilateral to the stimulated hindpaw, depression of BK-induced PE was already markedly enhanced, even in the absence of vagotomy. Ipsilateral DLF lesion (L-2/L-3) below the level of the spinal output to the adrenal medullae produced the same effect, suggesting interruption of a descending inhibitory pathway that relays the effect of vagal activity to the level of the capsaicin-induced nociceptive input. 4. Contralateral and ipsilateral hemisection of the spinal cord (C-5/C-6) produced the same changes as the corresponding DLF lesions. 5. Ipsi- or contralateral lesion of the dorsal funiculus at the spinal level T-8/T-9 had no effect on depression of BK-induced PE generated by cutaneous noxious stimulation of the forepaw. 6. We suggest that noxious stimulation activates an ascending pathway of the spino-bulbo-spinal excitatory circuit which projects through the DLF contralateral to the nociceptive input, and that the inhibitory pathway which is activated by vagal afferent activity projects through the DLF ipsilateral to the nociceptive input.