Naslov
Sulfasalazine blocks the development of tactile allodynia in diabetic rats

Autori
Berti-Mattera, L. N. ; Kern, T. S. ; Siegel, R. E. ; Nemet, Ina ; Mitchell, R.

Izvornik
Diabetes (New York, N.Y.) (0012-1797) 57 (2008), 10; 2801-2808

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
sulfasalazine ; tactile allodynia ; diabetic rats

Sažetak
Background/Objectives: Diabetic neuropathy is manifested either by loss of nociception (painless syndrome) or by mechanical hyperalgesia and tactile allodynia (pain in response to non-painful stimuli). While therapies with vasodilators or neurotrophins reverse some functional and metabolic abnormalities in diabetic nerves, they only partially ameliorate neuropathic pain. The reported link between nociception and targets of the anti-inflammatory drug sulfasalazine (SFZ) prompted us to investigate its effect on neuropathic pain in diabetes. Research Design: We examined the effects of SFZ, salicylates and the poly(ADP-ribose) polymerase-1 (PARP-1) inhibitor PJ34 on altered nociception in streptozotocin-induced diabetic rats. We also evaluated the levels of SFZ targets in sciatic nerves and dorsal root ganglia (DRG) of treated animals. Finally, we analyzed the development of tactile allodynia in diabetic mice lacking expression of the SFZ target nuclear factor kappa B (NF-κ B) p50. Results: SFZ completely blocked the development of tactile allodynia in diabetic rats, while relatively minor effects were observed with other salicylates and PJ34. Along with the behavioral findings, sciatic nerves and DRG from SFZ-treated diabetic rats displayed a decrease in NF-κ B p50 expression compared with untreated diabetic animals. Importantly, the absence of tactile allodynia in diabetic NF-κ B p50-/- mice supported a role for NF-κ B in diabetic neuropathy. SFZ treatment also increased inosine levels in sciatic nerves of diabetic rats. Conclusions: The complete inhibition of tactile allodynia in experimental diabetes by SFZ may stem from its ability to regulate both NF-κ B and inosine. SFZ might be useful in the treatment of nociceptive alterations in diabetic patients.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA