title: Negative feedback neuroendocrine control of inflammatory response in the rat is dependent on the sympathetic postganglionic neuron.
abstract: Negative feedback control of inflammation is mediated by activation of nociceptive afferents that in turn activates the hypothalamic-pituitary-adrenal axis to release corticosteroids. Plasma extravasation (PE) produced by the potent inflammatory mediator, bradykinin (BK), but not that induced by another potent inflammatory mediator, platelet-activating factor (PAF), is inhibited by released corticosterone. Because bradykinin, but not PAF, produces PE by a mechanism that is, in part, dependent on the sympathetic postganglionic neuron (SPGN) terminal, we tested the hypothesis that the negative feedback control of inflammation is dependent on the SPGN terminal in the inflamed tissue. In sympathectomized rats, the residual (i.e., SPGN-independent) PE in the knee joint produced by BK was not inhibited by noxious electrical stimulation. Furthermore, intravenous administration of corticosterone potently inhibited, with a similar time-course, the SPGN-dependent, but not the SPGN-independent, component of BK-induced PE. Neither electrical stimulation nor corticosterone inhibited PAF-induced PE. Finally, corticosterone's actions do not appear to be mediated by release of norepinephrine from the SPGN terminal, because neither the alpha-adrenergic receptor antagonist phentolamine nor the beta2-adrenergic receptor antagonist ICI 118, 551 antagonized the inhibition of BK-induced PE by corticosterone. We conclude that in the rat knee joint, negative feedback control of the inflammatory response is dependent on the presence of the SPGN terminal. Further, our data suggest that a significant component of corticosteroid-induced inhibition of PE produced by inflammatory mediators is SPGN-dependent.
authors.affiliation: Department of Oral Surgery, University of California, San Francisco, California 94143, USA.
authors.forename: P G
authors.initials: PG
authors.lastname: Green
authors.forename: W
authors.initials: W
authors.lastname: Jänig
authors.forename: J D
authors.initials: JD
authors.lastname: Levine
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000818:Animals; D001920:Bradykinin / Q000502:physiology*; D004558:Electric Stimulation; D005246:Feedback / Q000502:physiology*; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000305:Adrenal Cortex Hormones; D001920:Bradykinin