Sprouting of substance P-expressing primary afferent central terminals and spinal micturition reflex NK1 receptor dependence after spinal cord injury

Xiaoyang Zhang, Kristy L. Douglas, Huixia Jin, Bassem M. Eldaif, Rashid Nassar, Matthew O. Fraser, Paul C. Dolber

    Research output: Contribution to journalArticle

    15 Scopus citations

    Abstract

    The primary afferent neurotransmitter triggering the spinal micturition reflex after complete spinal cord injury (SCI) in the rat is unknown. Substance P detected immunohistochemically in the sacral parasympathetic nucleus was significantly higher in 12 SCI rats than in 12 spinally intact rats (P = 0.008), suggesting substance P as a plausible candidate for the primary afferent neurotransmitter. The effects of the tachykinin NK1 receptor antagonist L-733060 on the spinal micturition reflex were then determined by performing conscious cystometry in an additional 14 intact rats and 14 SCI rats with L-733060 (0.1-100 μg) administered intrathecally at L6-S1. L-733060 was without effect in intact rats, but blocked the spinal micturition reflex in 10 of 14 SCI rats and increased the intermicturition interval in 2 of 4 others at doses ranging from 10 to 100 μg. Both phasic and nonphasic voiding contractions, differentiated according to the presence of phasic external urethral sphincter (EUS) activity, were present in most SCI rats. Both types of contractions were blocked by high doses of L-733060. Interestingly, there was a relative decline in phasic voiding contractions at high doses as well as a decline in contraction amplitude in nonphasic voiding contractions. In other respects, cystometric variables were largely unaffected in either spinally intact or SCI rats. L-733060 did not affect tonic EUS activity at any dose except when the spinal micturition reflex was blocked and tonic activity was consequently lost. These experiments show that tachykinin action at spinal NK1 receptors plays a major role in the spinal micturition reflex in SCI rats.

    Original languageEnglish (US)
    Pages (from-to)R2084-R2096
    JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
    Volume295
    Issue number6
    DOIs
    StatePublished - Dec 1 2008

    Keywords

    • Bladder
    • External urethral sphincter
    • Spinal cord injury
    • Tachykinins

    ASJC Scopus subject areas

    • Physiology
    • Physiology (medical)

    Fingerprint Dive into the research topics of 'Sprouting of substance P-expressing primary afferent central terminals and spinal micturition reflex NK1 receptor dependence after spinal cord injury'. Together they form a unique fingerprint.

  • Cite this