Neural and endocrine mechanisms mediating noxious stimulus-induced inhibition of bradykinin plasma extravasation in the rat.
We studied the mechanisms by which activation of primary afferent nociceptors inhibits bradykinin-induced plasma extravasation in the rat. First, capsaicin, administered into the plantar surface of the hindpaw, dose-dependently inhibited bradykinin-induced plasma extravasation in the knee joint, a site distant from the noxious stimulus. The inhibitory effect of capsaicin was markedly attenuated after T(12)/L(1) spinal transection combined with lumbar preganglionic sympathectomy, which interrupts ascending spinal tracts to rostral sites and to spinal sympathetic and sympathoadrenal outflow. Second, interruption of the sympathetics (cutting the L(1-3) white rami) or surgical adrenal denervation significantly attenuated capsaicin-induced inhibition of bradykinin-induced plasma extravasation. Interruption of the sympathoadrenal pathway produced the largest attenuation. Lesioning of the hypothalamic-pituitary-adrenal axis did not affect the inhibitory action of capsaicin. Third, intra-articular perfusion with phentolamine (10(-5) M, an alpha-adrenoceptor antagonist), propranolol (10(-5) M, a beta-adrenoceptor antagonist), and naloxone (10(-5) M, an opioidergic receptor antagonist) each attenuated the inhibitory action of capsaicin. Propranolol and naloxone produced the largest attenuation. Blocking glucocorticoid receptors (RU-38, 486, 30 mg/kg s.c.) did not affect the inhibitory action of intraplantar capsaicin. Fourth, the magnitude of the attenuation of capsaicin-induced inhibition of bradykinin-induced plasma extravasation after a combined treatment of surgical lumbar sympathetic decentralization with intra-articular phentolamine or surgical adrenal denervation with intra-articular propranolol or naloxone was similar to each of the surgical or pharmacological treatments of the same axis alone. These results support the suggestion that two neural/endocrine circuits, sympathoadrenal and sympathetic, account for most, if not all, of nociceptor activity-induced inhibition of bradykinin-induced plasma extravasation produced by capsaicin.
Miao
F J
FJ
Department of Medicine, University of California at San Francisco, Schools of Medicine and Dentistry, San Francisco, California 94143-0440, USA. fjmiao@itsa.ucsf.edu
Levine
J D
JD
D000311:Adrenal Glands / Q000294:innervation / Q000502:physiology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D002211:Capsaicin / Q000008:administration & dosage / Q000494:pharmacology; D004558:Electric Stimulation; D004702:Endocrine Glands / Q000502:physiology*; D007016:Hypophysectomy; D007719:Knee Joint / Q000502:physiology; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009424:Nervous System Physiological Phenomena; D009475:Neurons, Afferent / Q000502:physiology; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology; D013582:Synovial Fluid / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D009292:Narcotic Antagonists; D015735:Mifepristone; D009270:Naloxone; D011433:Propranolol; D002211:Capsaicin; D001920:Bradykinin; D010646:Phentolamine