Contribution of C-fiber afferent nerves and autonomic pathways in the urinary bladder to spinal c-fos expression induced by bladder irritation.
Previous studies have revealed that chemical irritation of the urinary bladder and urethral mucosa increases the expression of the immediate-early gene, c-fos, in the lumbosacral spinal cord of the rat. The present experiments were undertaken to determine whether drugs known to suppress bladder reflex pathways or spinal nociceptive mechanisms would influence c-fos expression induced by chemical irritation of the lower urinary tract (LUT). Capsaicin (100 mg/kg subcutaneous (s.c.), 7 days prior to the experiment) which does not block bladder reflexes but does desensitize C-fiber afferents, reduced (89%) the number of Fos-positive cells in the lumbosacral spinal cord induced by acetic acid-induced irritation of the LUT. Morphine (2.5 mg/kg, intravenous (i.v.)) or a low dose of baclofen, a GABA(B) agonist, both of which markedly suppressed reflex bladder activity, did not alter spinal c-fos expression induced by LUT irritation. However, a larger dose of baclofen (10 mg/kg, i.v.) reduced by 45% the number of Fos-positive cells. Clonidine (200 microg/kg, i.v.), an alpha2 adrenergic agonist, depressed bladder reflexes but produced only a small decrease (25%) in c-fos expression in lateral laminae V-VII of the cord. The ganglionic blocking agent, hexamethonium, which blocks autonomic but not afferent pathways to the LUT, decreased c-fos expression by 50%. The results indicate that certain drugs can differentially affect reflex bladder activity and c-fos expression and that analgesic drugs which suppress somatic nociceptive pathways do not necessarily affect the c-fos expression induced by visceral nociceptive input.
Birder
L A
LA
University of Pittsburgh, PA 15261, USA. Lbirder+@pitt.edu
de Groat
W C
WC
D019342:Acetic Acid / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000344:Afferent Pathways / Q000502:physiology; D000818:Animals; D001341:Autonomic Nervous System / Q000502:physiology*; D001418:Baclofen / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D007509:Irritants / Q000494:pharmacology*; D009412:Nerve Fibers / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects* / Q000294:innervation
D000316:Adrenergic alpha-Agonists; D018755:GABA Agonists; D007509:Irritants; D016760:Proto-Oncogene Proteins c-fos; D001418:Baclofen; D003000:Clonidine; D019342:Acetic Acid; D002211:Capsaicin