INHIBITION OF SPINAL 5-HT3R REVERTED DIABETES-INDUCED MECHANICAL HYPERSENSITIVITY IN A GABA(A)R-MEDIATED NEUROTRANSMISSION-DEPENDENT MANNER

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

Authors

Silva, M (Author) Other; Martins, D (Author) Other; Isaura Tavares (Author) FMUP; Morgado, C (Author) Other

Journal

Title: Neuroscience

Vol. 304

Pages: 228-239

ISSN: 0306-4522

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 1 Citation

Other information

Authenticus ID: P-00G-KHV

DOI: 10.1016/j.neuroscience.2015.07.050

Abstract (EN): Spinal 5-HT3 receptor (5-HT3R) has been implicated in chronic pain development. The extent to which 5-HT3R contributes to spinal sensitization and diabetic neuropathic pain (DNP) remains elusive and the mechanisms subserving the effects of 5-HT3R activation on spinal pain processing during chronic pain are still unclear. In this study, we evaluated the contribution of spinal 5-HT3R to pain facilitation and spinal sensitization during DNP, exploiting the role of GABA(A)R-mediated neurotransmission and glial activation in the effects elicited by intrathecal administration of a 5-HT3R antagonist. Mechanical nociception was evaluated by paw pressure test in streptozotocin (STZ)-diabetic and control rats after intrathecal (i.t.) administration of a 5-HT3R antagonist (Y25130). The spinal activation of extracellular signal-regulated kinases (ERKs) pathway and the expression of 5-HT3R, glial fibrillary acidic protein (GFAP; marker of astroglia activation) and ionized calcium binding adaptor molecule 1 (IBA-1; marker of microglia activation) were evaluated at the peak maximum effect of Y25130. The involvement of GABA(A)R-mediated neurotransmission in the behavioral pain effect of Y25130, was assessed in STZ-diabetic animals receiving i.t. administrations of muscimol (GABA(A)R agonist). Intrathecal administration of Y25130 reverted mechanical hyperalgesia and decreased the activation of ERKs in STZ-diabetic rats, while no effects were observed in control animals. The spinal activation of GABA(A)R by i.t. administration of muscimol abolished Y25130-driven antinociception. The expression of IBA-1, GFAP and 5-HT3R was unaltered by treatment. These findings point to a GABA-mediated pronociceptive role of spinal 5-HT3R during DNP.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12