Activity, Motor Control & Coordination
Pain - Thermal Allodynia / Hyperalgesia
Pain - Spontaneous Pain - Postural Deficit
Pain - Mechanical Allodynia / Hyperalgesia
Anxiety & Depression Disorder
Learning/Memory - Attention - Addiction
Physiology & Respiratory Research
Metabolism - Food & Drink Intake
Pain
Central Nervous System (CNS)
Neurodegeneration
Sensory system
Motor control
Mood Disorders
Other disorders
Muscular system
Joints
Metabolism
Cross-disciplinary subjects
Preclinical studies and opioids: role in crisis management in the United States Authors
M Kremer, I Yalcin, Y Goumon, X Wurtz, L Nexon et al
Lab
Centre National de la Recherche Scientifique, Université de Strasbourg, Institut des Neurosciences Cellulaires et Intégratives, Strasbourg, France.
Journal
Journal of Neuroscience
Abstract
Beside depression, antidepressant drugs are also a first-line treatment for neuropathic pain, which is consecutive to a lesion or pathology of the nervous system. Despite a widespread use of these drugs, the mechanism underlying their therapeutic action in this pain context remains partly elusive. The present study combined data collected in male and female mice from a model of neuropathic pain and data from the clinics to understand how antidepressant drugs act. We showed two distinct mechanisms by which the selective inhibitor of serotonin and noradrenaline reuptake duloxetine and the tricyclic antidepressant amitriptyline relieved neuropathic allodynia. One of these mechanisms is acute, central, and requiring descending noradrenergic inhibitory controls and _2A adrenoceptors, as well as the mu and delta opioid receptors. The second mechanism is delayed, peripheral and requires noradrenaline from peripheral sympathetic endings and _2 adrenoceptors, as well as the delta opioid receptors. We then conducted a transcriptomic analysis in dorsal root ganglia which suggested that the peripheral component of duloxetine action involves the inhibition of neuroimmune mechanisms accompanying nerve injury, including the downregulation of the TNF_-NF_B signaling pathway. Accordingly, immunotherapies against either TNF_ or TLR2 provided allodynia relief. We also compared duloxetine plasma levels in the animal model and in patients and we observed that patients drug concentrations are compatible with those measured in animals under chronic treatment involving the peripheral mechanism. Our study highlights a peripheral neuroimmune component of antidepressant drugs that is relevant to their delayed therapeutic action against neuropathic pain.
BIOSEB Instruments Used:
Von Frey Filaments (Bio-VF-M)
