title: Reduction of spinal sensory transmission by facilitation of 5-HT1B/D receptors in noninjured and spinal cord-injured humans.
abstract: Activation of receptors by serotonin (5-HT1) and norepinephrine (α2) on primary afferent terminals and excitatory interneurons reduces transmission in spinal sensory pathways. Loss or reduction of descending sources of serotonin and norepinephrine after spinal cord injury (SCI) and the subsequent reduction of 5-HT1/α2 receptor activity contributes, in part, to the emergence of excessive motoneuron activation from sensory afferent pathways and the uncontrolled triggering of persistent inward currents that depolarize motoneurons during muscle spasms. We tested in a double-blind, placebo-controlled study whether facilitating 5-HT1B/D receptors with the agonist zolmitriptan reduces the sensory activation of motoneurons during an H-reflex in both noninjured control and spinal cord-injured participants. In both groups zolmitriptan, but not placebo, reduced the size of the maximum soleus H-reflex with a peak decrease to 59% (noninjured) and 62% (SCI) of predrug values. In SCI participants we also examined the effects of zolmitriptan on the cutaneomuscular reflex evoked in tibialis anterior from stimulation to the medial arch of the foot. Zolmitriptan, but not placebo, reduced the long-latency, polysynaptic component of the cutaneomuscular reflex (first 200 ms of reflex) by ∼50%. This ultimately reduced the triggering of the long-lasting component of the reflex (500 ms poststimulation to end of reflex) known to be mediated by persistent inward currents in the motoneuron. These results demonstrate that facilitation of 5-HT1B/D receptors reduces sensory transmission in both monosynaptic and polysynaptic reflex pathways to ultimately reduce long-lasting reflexes (spasms) after SCI.
authors.affiliation: Centre for Neuroscience, Univ. of Alberta, 5-005 Katz Group - Rexall Centre, Edmonton, AB, Canada T6G 2E1.
authors.forename: Jessica M
authors.initials: JM
authors.lastname: D'Amico
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Li
authors.forename: David J
authors.initials: DJ
authors.lastname: Bennett
authors.forename: Monica A
authors.initials: MA
authors.lastname: Gorassini
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006181:H-Reflex / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism / Q000502:physiology; D009128:Muscle Spasticity / Q000378:metabolism / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000294:innervation / Q000503:physiopathology; D023303:Oxazolidinones / Q000494:pharmacology*; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D044346:Receptor, Serotonin, 5-HT1D / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000503:physiopathology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014363:Tryptamines / Q000494:pharmacology*
chemical_list: D023303:Oxazolidinones; D044302:Receptor, Serotonin, 5-HT1B; D044346:Receptor, Serotonin, 5-HT1D; D018341:Receptors, Adrenergic, alpha-2; D058825:Serotonin 5-HT1 Receptor Agonists; D014363:Tryptamines; C089750:zolmitriptan