Differential modulatory effects of cholera toxin and pertussis toxin on pain behavior induced by TNF-alpha, interleukin-1beta and interferon-gamma injected intrathecally.
The present study was designed to characterize the possible roles of spinally located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in pro-inflammatory cytokine induced pain behaviors. Intrathecal injection of tumor necrosis factor-alpha (TNF-alpha; 100 pg), interleukin-1beta (IL-1beta; 100 pg) and interferon-gamma (INF-gamma; 100 pg) showed pain behavior. Intrathecal pretreatment with CTX (0.05, 0.1 and 0.5 mg) attenuated pain behavior induced by TNF-alpha and INF-gamma administered intrathecally. But intrathecal pretreatment with CTX (0.05, 0.1 and 0.5 microg) did not attenuate pain behavior induced by IL-1beta. On the other hand, intrathecal pretreatment with PTX further increased the pain behavior induced by TNF-alpha and IL-1beta administered intrathecally, especially at the dose of 0.5 microg. But intrathecal pretreatment with PTX did not affect pain behavior induced by INF-gamma. Our results suggest that, at the spinal cord level, CTX- and PTX-sensitive G-proteins appear to play important roles in modulating pain behavior induced by pro-inflammatory cytokines administered spinally. Furthermore, TNF-alpha, IL-1beta and INF-gamma administered spinally appear to produce pain behavior by different mechanisms.
Department of Pharmacology, College of Medicine, and Institute of Natural Medicine, Hallym University, Gangwon-Do 200-702, Korea.
Min-Soo
MS
Kwon
Eon-Jeong
EJ
Shim
Young-Jun
YJ
Seo
Seong-Soo
SS
Choi
Jin-Young
JY
Lee
Han-Kyu
HK
Lee
Hong-Won
HW
Suh
D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000502:physiology; D006930:Hyperalgesia / Q000139:chemically induced* / Q000517:prevention & control; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D037342:Pertussis Toxin / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002772:Cholera Toxin; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins