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
Metabolism
Motor control
Neurodegeneration
Cross-disciplinary subjects
Muscular system
General activity
Mood Disorders
Other disorders
Joints
Central Nervous System (CNS)
Sensory system
Authors
Kerckhove N, Mallet C, François A, Boudes M, Chemin J, Voets T, Bourinet E, Alloui A, Eschalier A
Lab
Clermont Université, Université d'Auvergne, Pharmacologie Fondamentale et Clinique de la Douleur, 63000 Clermont-Ferrand, France
Journal
Pain.
Abstract
To exert its analgesic action, paracetamol requires complex metabolism to produce a brain-specific lipoamino acid compound, AM404, which targets central transient receptor potential vanilloid receptors (TRPV1). Lipoamino acids are also known to induce analgesia through T-type calcium-channel inhibition (Ca(v)3.2). In this study we show that the antinociceptive effect of paracetamol in mice is lost when supraspinal Ca(v)3.2 channels are inhibited. Therefore, we hypothesized a relationship between supraspinal Ca(v)3.2 and TRPV1, via AM404, which mediates the analgesic effect of paracetamol. AM404 is able to activate TRPV1 and weakly inhibits Ca(v)3.2. Interestingly, activation of TRPV1 induces a strong inhibition of Ca(v)3.2 current. Supporting this, intracerebroventricular administration of AM404 or capsaicin produces antinociception that is lost in Ca(v)3.2(-/-) mice. Our study, for the first time, (1) provides a molecular mechanism for the supraspinal antinociceptive effect of paracetamol; (2) identifies the relationship between TRPV1 and the Ca(v)3.2 channel; and (3) suggests supraspinal Ca(v)3.2 inhibition as a potential pharmacological strategy to alleviate pain.
BIOSEB Instruments Used:
Von Frey Filaments (Bio-VF-M)
