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Constitutively active 5-HT2/α1 receptors facilitate muscle spasms after human spinal cord injury
- Publication Year :
- 2012
- Publisher :
- American Physiological Society, 2012.
-
Abstract
- In animals, the recovery of motoneuron excitability in the months following a complete spinal cord injury is mediated, in part, by increases in constitutive serotonin (5-HT2) and norepinephrine (α1) receptor activity, which facilitates the reactivation of calcium-mediated persistent inward currents (CaPICs) without the ligands serotonin and norepinephrine below the injury. In this study we sought evidence for a similar role of constitutive monoamine receptor activity in the development of spasticity in human spinal cord injury. In chronically injured participants with partially preserved sensory and motor function, the serotonin reuptake inhibitor citalopram facilitated long-lasting reflex responses (spasms) previously shown to be mediated by CaPICs, suggesting that in incomplete spinal cord injury, functional descending sources of monoamines are present to activate monoamine receptors below the lesion. However, in participants with motor or motor/sensory complete injuries, the inverse agonist cyproheptadine, which blocks both ligand and constitutive 5-HT2/α1 receptor activity, decreased long-lasting reflexes, whereas the neutral antagonist chlorpromazine, which only blocks ligand activation of these receptors, had no effect. When tested in noninjured control participants having functional descending sources of monoamines, chlorpromazine was effective in reducing CaPIC-mediated motor unit activity. On the basis of these combined results, it appears that in severe spinal cord injury, facilitation of persistent inward currents and muscle spasms is mainly mediated by the activation of constitutive 5-HT2 and α1 receptor activity. Drugs that more selectively block these constitutively active monoamine receptors may provide better oral control of spasticity, especially in motor complete spinal cord injury where reducing motoneuron excitability is the primary goal.
- Subjects :
- Adult
Male
Recruitment, Neurophysiological
Physiology
Chlorpromazine
Serotonin reuptake inhibitor
Action Potentials
Pharmacology
Citalopram
Norepinephrine
Receptors, Adrenergic, alpha-1
Reflex
medicine
Humans
Biogenic Monoamines
Receptor, Serotonin, 5-HT2A
Spasticity
Receptor
Muscle, Skeletal
Spinal cord injury
Spinal Cord Injuries
Aged
Motor Neurons
business.industry
General Neuroscience
Articles
Middle Aged
medicine.disease
Motor unit
Monoamine neurotransmitter
Muscle Spasticity
Case-Control Studies
Dopamine Antagonists
Calcium
Female
Serotonin
medicine.symptom
business
Neuroscience
Selective Serotonin Reuptake Inhibitors
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....8272a9af0e5ccb6534eb506a31a94bfd