Neuropeptide Modulation of a Lumbar Spinal Reflex: Potential Implications for Female Sexual Function

Authors


V. Margaret Jackson, Pfizer, Eastern Point Rd, Groton CT 06340 USA. Tel: (860) 715-3817; Fax: (860) 686 0565; E-mail: margaret.jackson@pfizer.com

ABSTRACT

Introduction.  Neuropeptides are known to modulate female receptivity. However, even though receptivity is a spinal reflex, the role of neuropeptides within the spinal cord remains to be elucidated.

Aim.  The aims were to (i) investigate neuropeptides in the lumbosacral region; and (ii) determine how neuropeptides modulate glutamate release from stretch Ia fibers, touch sensation Aβ fibers and Aδ/C pain fibers.

Main Outcome Measures.  Neuropeptide modulation of the lumbosacral dorsal-root ventral-root reflex in vitro.

Methods.  Spinal cords were removed from Sprague-Dawley rats in compliance with UK Home Office guidelines. Hemisected cords were superfused with aCSF and the dorsal root (L4–S1) was stimulated to evoke glutamate release. A biphasic reflex response was evoked from the opposite ventral root consisting of a monosynaptic (Ia fibers) and polysynaptic (Aβ, Aδ/C fibers) component.

Results.  The µ opioid receptor (MOR) agonist DAMGO inhibited the monosynaptic (EC50 0.02 ± 0.02 nM) and polysynaptic area (EC50 125 ± 167 nM) but not polysynaptic amplitude. Oxytocin and corticotrophin releasing factor (CRF) inhibited the monosynaptic amplitude (EC50, 1.4 ± 1.0 nM and EC50 4.3 ± 3.5 nM, respectively), polysynaptic amplitude (EC50 18.2 ± 28.0 nM and EC50, 9.5 ± 13.3 nM, respectively), and area (EC50 11.6 ± 13.0 nM and EC50, 2.8 ± 3.3 nM, respectively); effects that were abolished by oxytocin and CRF1 antagonists, L-368899 and 8w. Melanocortin agonists solely inhibited the monosynaptic component, which were blocked by the MC3/4 receptor antagonist SHU9119.

Conclusion.  These data suggest endogenous neuropeptides are released within the lumbosacral spinal cord. Melanocortin agonists, oxytocin, CRF, and DAMGO via MC4, oxytocin, CRF1, and MOR inhibit glutamate release but with differing effects on afferent fiber subtypes. Melanocortins, oxytocin, CRF, and DAMGO have the ability to modulate orgasm whereas oxytocin, CRF and DAMGO can increase pain threshold. Oxytocin and CRF may dampen touch sensation. Wilson LA, Wayman CP, and Jackson MV. Neuropeptide modulation of a lumbar spinal reflex: Potential implications for female sexual function. J Sex Med **;**:**–**.

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