gw9508 has been researched along with Neuralgia* in 2 studies
2 other study(ies) available for gw9508 and Neuralgia
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Activation of GPR40 produces mechanical antiallodynia via the spinal glial interleukin-10/β-endorphin pathway.
The G protein-coupled receptor 40 (GPR40), broadly expressed in various tissues such as the spinal cord, exerts multiple physiological functions including pain regulation. This study aimed to elucidate the mechanisms underlying GPR40 activation-induced antinociception in neuropathic pain, particularly related to the spinal glial expression of IL-10 and subsequent β-endorphin.. Spinal nerve ligation-induced neuropathic pain model was used in this study. β-Endorphin and IL-10 levels were measured in the spinal cord and cultured primary microglia, astrocytes, and neurons. Double immunofluorescence staining of β-endorphin with glial and neuronal cellular biomarkers was also detected in the spinal cord and cultured primary microglia, astrocytes, and neurons.. GPR40 was expressed on microglia, astrocytes, and neurons in the spinal cords and upregulated by spinal nerve ligation. Intrathecal injection of the GPR40 agonist GW9508 dose-dependently attenuated mechanical allodynia and thermal hyperalgesia in neuropathic rats, with E. Our results illustrate that GPR40 activation produces antinociception via the spinal glial IL-10/β-endorphin antinociceptive pathway. Topics: Animals; Animals, Newborn; beta-Endorphin; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Gene Expression Regulation; Hyperalgesia; Interleukin-10; Male; Methylamines; Nerve Tissue Proteins; Neuralgia; Neuroglia; Pain Measurement; Propionates; Rats; Rats, Wistar; Receptors, G-Protein-Coupled; RNA, Messenger; Signal Transduction | 2019 |
Attenuation of inflammatory and neuropathic pain behaviors in mice through activation of free fatty acid receptor GPR40.
The G-protein-coupled receptor 40 (GPR40) is suggested to function as a transmembrane receptor for medium- to long-chain free fatty acids and is implicated to play a role in free fatty acids-mediated enhancement of glucose-stimulated insulin secretion from pancreas. However, the functional role of GPR40 in nervous system including somatosensory pain signaling has not been fully examined yet.. Intrathecal injection of GPR40 agonist (MEDICA16 or GW9508) dose-dependently reduced ipsilateral mechanical allodynia in CFA and SNL models and thermal hyperalgesia in carrageenan model. These anti-allodynic and anti-hyperalgesic effects were almost completely reversed by a GPR40 antagonist, GW1100. Immunohistochemical analysis revealed that GPR40 is expressed in spinal dorsal horn and dorsal root ganglion neurons, and immunoblot analysis showed that carrageenan or CFA inflammation or spinal nerve injury resulted in increased expression of GPR40 in these areas. Patch-clamp recordings from spinal cord slices exhibited that bath-application of either MEDICA16 or GW9508 significantly decreased the frequency of spontaneous excitatory postsynaptic currents in the substantia gelatinosa neurons of the three pain models.. Our results indicate that GPR40 signaling pathway plays an important suppressive role in spinal nociceptive processing after inflammation or nerve injury, and that GPR40 agonists might serve as a new class of analgesics for treating inflammatory and neuropathic pain. Topics: Analgesics; Animals; Behavior, Animal; Disease Models, Animal; Excitatory Postsynaptic Potentials; Fatty Acids, Nonesterified; Ganglia, Spinal; Inflammation; Male; Methylamines; Mice, Inbred C57BL; Neuralgia; Neurons; Propionates; Receptors, G-Protein-Coupled; Spinal Nerves | 2015 |