1. Functional interaction between TRPV1 and mu-opioid receptors in the descending antinociceptive pathway activates glutamate transmission and induces analgesia
- Author
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Francesca Guida, Livio Luongo, Katarzyna Starowicz, Vito de Novellis, Sabatino Maione, Francesca Rossi, Enza Palazzo, Luigia Cristino, Ida Marabese, Vincenzo Di Marzo, Maione, Sabatino, Starowicz, K, Cristino, L, Guida, Francesca, Palazzo, Enza, Luongo, Livio, Rossi, Francesca, Marabese, Ida, DE NOVELLIS, Vito, and DI MARZO, V.
- Subjects
Male ,Pain Threshold ,Enkephalin ,Microinjections ,Physiology ,TRPV1 ,Receptors, Opioid, mu ,Action Potentials ,Glutamic Acid ,TRPV Cation Channels ,Transient receptor potential channel ,medicine ,Reaction Time ,Animals ,Periaqueductal Gray ,Rats, Wistar ,Receptor ,Pain Measurement ,Medulla Oblongata ,Dose-Response Relationship, Drug ,Chemistry ,Naloxone ,General Neuroscience ,Glutamate receptor ,Enkephalin, Ala(2)-MePhe(4)-Gly(5) ,Peripheral ,Rats ,Nociception ,Opioid ,nervous system ,Hyperalgesia ,lipids (amino acids, peptides, and proteins) ,Capsaicin ,Diterpenes ,Neuroscience ,medicine.drug - Abstract
The transient receptor potential vanilloid-1 (TRPV1) receptor is involved in peripheral and spinal nociceptive processing and is a therapeutic target for pain. We have shown previously that TRPV1 in the ventrolateral periaqueductal gray (VL-PAG) tonically contributes to brain stem descending antinociception by stimulating glutamate release into the rostral ventromedial medulla and off neuron activity. Because both opioid and vanilloid systems integrate and transduce pain sensation in these pathways, we studied the potential interaction between TRPV1 and μ-opioid receptors in the VL-PAG–rostral ventromedial medulla (RVM) system. We found that the TRPV1 agonist, capsaicin, and the μ-receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin, when coadministered into the ventrolateral-PAG at doses nonanalgesic per se, produce 1) antinociception in tests of thermal nociception; 2) stimulation of glutamate release into the RVM; and 3) inhibition of on neuron activity in the RVM. These effects were all antagonized by the TRPV1 and opioid receptor antagonists 5′-iodo-resiniferatoxin and naloxone, respectively, thus suggesting the existence of a TRPV1–μ-opioid interaction in the VL-PAG–RVM system. By using double immunofluorescence techniques, we found that TRPV1 and μ-opioid receptors are coexpressed in several neurons of the VL-PAG. These findings suggest that μ-receptor activation not only acts on inhibitory neurons to disinhibit PAG output neurons but also interacts with TRPV1 activation at increasing glutamate release into the RVM, possibly by acting directly on PAG output neurons projecting to the RVM.
- Published
- 2009