GABA acting on GABA(B) receptors located in a medullary pain facilitatory area enhances nociceptive behaviors evoked by intraplantar formalin injection

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Maria Isabel Martins (Author) FMUP; Carvalho, P (Author) Other; de Vries, MG (Author) Other; Teixeira Pinto, A (Author) Other; Wilson, SP (Author) Other; Westerink, BHC (Author) Other; Isaura Tavares (Author) FMUP

Journal

Title: Pain

Vol. 156

Pages: 1555-1565

ISSN: 0304-3959

Publisher: Wolters Kluwer Health

Indexing

ISI Web of Knowledge - 10 Citations

Scopus - 11 Citations

Other information

Authenticus ID: P-00G-FJB

DOI: 10.1097/j.pain.0000000000000203

Abstract (EN): The dorsal reticular nucleus (DRt) plays a key role in facilitation of nociceptive transmission at the spinal cord. In this study, we evaluated the mechanisms involved in GABA-mediated control of the DRt focusing on the role of local GABA(B) receptors. First, we used in vivo microdialysis to study the release of GABA in the DRt during the course of the formalin test. An increase of GABA levels in comparison with baseline values was detected in the second phase of the test. Because we previously showed that GABA(B) receptors are expressed by opioidergic DRt neurons, which respond to nociceptive stimuli and inhibit spinally projecting DRt neurons involved in descending pronociception, we then interfered with local GABA(B) receptors using gene transfer and pharmacological approaches. Lentiviral-mediated knockdown of GABA(B1a) expression decreased nociceptive responses during the second phase of the test. Local administration of the GABA(B) receptor antagonist CGP 35348 also decreased nociceptive responses in the second phase of the test, whereas the opposite was detected after injection of the GABA(B) agonist baclofen. Finally, we determined the GABAergic afferents of the DRt, namely those arising from its main brain afferents, which are located at the telencephalon and diencephalon. For that purpose, we combined retrograde tract-tracing from the DRt with immunodetection of glutamate decarboxylase, the GABA-synthesizing enzyme. The higher numbers of retrogradely labelled glutamate decarboxylase-immunoreactive neurons were located at insular, somatosensory, and motor cortices. Collectively, the results suggest that GABA acting on GABA(B) receptors may enhance pain facilitation from the DRt during inflammatory pain.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11