Induction of nociceptive responses by intrathecal injection of interleukin-1 in mice.
Intrathecal (i.t.) injection (between lumbar vertebrae 5 and 6) into mice of a markedly low dose of IL-1alpha (3x10(-4) fmol or 5.4 fg in 5 microl per mouse) induced behaviors involving scratching, biting, and licking of non-stimulated hindpaws. The IL-1-induced behaviors appeared within 10 min of the injection of IL-1alpha, peaked at 20-40 min, and had disappeared 60 min after the injection. The IL-1-induced behaviors were similar to the nociceptive responses induced in mice by i.t. injection of substance P (SP) or subcutaneous (s.c.) injection of formalin into the footpad. The IL-1-induced behaviors were suppressed by intraperitoneal morphine, indicating that they are nociceptive responses. The nociceptive responses induced by 3x10(-4) (5.4 fg) of IL-1alpha were almost completely suppressed by co-injection of 0.3 fmol (7.2 pg) of an IL-1 receptor antagonist (IL-1ra). An antiserum against substance P, but not an antiserum against somatostatin, suppressed the IL-1-induced nociceptive responses. The nociceptive responses induced by s.c. injection of 2% formalin into the footpad were also inhibited by i.t. injection of 30 pmol (720 ng) of IL-1ra. These results suggest that IL-1 may play a role in hyperalgesia in mice by acting as a factor augmenting pain transmission in the spinal cord at least in part by either directly or indirectly releasing substance P.
Tadano
T
T
Department of Pharmacology, Tohoku College of Pharmacy, Sendai, Japan.
Namioka
M
M
Nakagawasai
O
O
Tan-No
K
K
Matsushima
K
K
Endo
Y
Y
Kisara
K
K
D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007106:Immune Sera / Q000494:pharmacology; D007278:Injections, Spinal; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013004:Somatostatin / Q000276:immunology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000276:immunology
D000700:Analgesics; D007106:Immune Sera; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D013373:Substance P; D013004:Somatostatin