Neuropeptide modulation of a lumbar spinal reflex: potential implications for female sexual function.
BACKGROUND
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.


OBJECTIVE
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 Abeta fibers and Adelta/C pain fibers.


METHODS
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 (Abeta, Adelta/C fibers) component.


RESULTS
The micro opioid receptor (MOR) agonist DAMGO inhibited the monosynaptic (EC(50) 0.02 +/- 0.02 nM) and polysynaptic area (EC(50) 125 +/- 167 nM) but not polysynaptic amplitude. Oxytocin and corticotrophin releasing factor (CRF) inhibited the monosynaptic amplitude (EC(50), 1.4 +/- 1.0 nM and EC(50) 4.3 +/- 3.5 nM, respectively), polysynaptic amplitude (EC(50) 18.2 +/- 28.0 nM and EC(50), 9.5 +/- 13.3 nM, respectively), and area (EC(50) 11.6 +/- 13.0 nM and EC(50), 2.8 +/- 3.3 nM, respectively); effects that were abolished by oxytocin and CRF(1) antagonists, L-368899 and 8w. Melanocortin agonists solely inhibited the monosynaptic component, which were blocked by the MC(3/4) receptor antagonist SHU9119.


CONCLUSIONS
These data suggest endogenous neuropeptides are released within the lumbosacral spinal cord. Melanocortin agonists, oxytocin, CRF, and DAMGO via MC(4), oxytocin, CRF(1), 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
Lesley A
LA
Pfizer Global Research & Development-Discovery Biology, Sandwich, Kent, UK.
Wayman
Chris P
CP
Pfizer Global Research & Development-Discovery Biology, Sandwich, Kent, UK.
Jackson
V Margaret
VM
Pfizer Global Research & Development-Discovery Biology, Sandwich, Kent, UK. Electronic address: margaret.jackson@pfizer.com.
D000818:Animals; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D008159:Lumbar Vertebrae; D009479:Neuropeptides / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects; D012018:Reflex / Q000502:physiology*; D012023:Reflex, Monosynaptic / Q000187:drug effects; D012726:Sexual Behavior, Animal; D013116:Spinal Cord / Q000187:drug effects / Q000601:surgery; D013126:Spinal Nerve Roots / Q000378:metabolism*; D013131:Spine / Q000378:metabolism*
D009479:Neuropeptides; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D018698:Glutamic Acid