American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Mar 2005
Elimination of rat spinal neurons expressing neurokinin 1 receptors reduces bladder overactivity and spinal c-fos expression induced by bladder irritation.
Substance P (SP) binding to neurokinin 1 receptors (NK1R) in the spinal cord reportedly plays an important role in the micturition reflex as well as in nociceptive responses. We therefore investigated the effect of ablation of NK1R-expressing neurons in the spinal cord using saporin, a ribosome-inactivating protein, conjugated with [Sar9, Met (O2)11]SP, a specific ligand of NK1R (SSP-saporin), on the micturition reflex in rats. In female Sprague-Dawley rats, SSP-saporin (1.0 or 1.5 microM) or saporin (1.5 microM) only was injected through an intrathecal catheter implanted at the L6-S1 level of the spinal cord. ⋯ SSP-saporin treatment also decreased c-fos expression in the dorsal horn of the spinal cord induced by instillation of capsaicin into the bladder. These data indicate that NK1R-expressing neurons in the superficial layer of the dorsal horn play an important role in transmission of nociceptive afferent information from the bladder to induce bladder overactivity and spinal c-fos expression elicited by bladder irritation. Toxin-induced damage of NK1R-expressing neurons in the lumbosacral spinal cord may provide an effective modality for treating overactivity and/or nociceptive responses in the bladder without affecting normal micturition.