Instituut voor Neuropathische Pijn
English articles Gliopathic pain Glia modulator propentofyllin not active on human non-neuronal cells
| Glia modulator propentofyllin not active on human non-neuronal cells |
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Glial cells are involved in neuropathic pain conditions. Several glial-targeted agents are in development for the treatment of pain conditions. The glial modulating agent, propentofylline, did however not decrease pain reported in association with post-herpetic neuralgia. Why? Because the human non-neuronal cells do not listen to this glia modulator, although rat non neuronal cells do....
The authors measured tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and nitrite release (as an indicator of NO) as downstream indicators and found that LPS treatment did not induce nitrite in human microglia, macrophages or THP-1 cells; however LPS treatment did induce nitrite release in rat microglia and macrophages. Propentofylline blocked TNF-α release in rodent microglia with all the doses tested (1-100μM), and dose-dependently decreased TNF-α release in rodent macrophages. Propentofylline partially decreased TNF-α (35%) at 100μM in human microglia, macrophages and THP-1 macrophages. Propentofylline blocked nitrite release from LPS stimulated rat microglia and inhibited nitrite in LPS-stimulated rat macrophages. IL-1β was decreased in LPS-stimulated human microglia following propentofylline at 100μM. Human microglia appeared to be much less responsive to LPS stimulation and propentofylline treatment than the other cell types. This all explain the differential behavioral effects of propentofylline in rat compared to men.[1] December 2011, J M Keppel Hesselink, MD, PhD Referenties[1]: Landry RP, Jacobs VL, Romero-Sandoval EA, Deleo JA. | Propentofylline, a CNS glial modulator does not decrease pain in post-herpetic neuralgia patients: In vitro evidence for differential responses in human and rodent microglia and macrophages. | Exp Neurol. | 2011 Nov 15. [Epub ahead of print] |