Induction of nociceptive responses by intrathecal injection of interleukin-1 in mice

Intrathecal (i.t.) injection (between lumbar vertebrae 5 and 6) into mice o f a markedly low dose of IL-1 alpha (3x10(-4) fmol or 5.4 fg in 5 mu l per mouse) induced behaviors involving scratching, biting, and licking of non-s timulated hindpaws. The IL-1-induced behaviors appeared within 10 min of th e injection of IL-1 alpha, peaked at 20-40 min, and had disappeared 60 min after the injection. The IL-1-induced behaviors were similar to the nocicep tive responses induced in mice by i.t. injection of substance P (SP) or sub cutaneous (s.c.) injection of formalin into the footpad. The IL-1-induced b ehaviors were suppressed by intraperitoneal morphine, indicating that they are nociceptive responses. The nociceptive responses induced by 3x10(-4)(5. 4 fg) of IL-1 alpha were almost completely suppressed by co-injection of 0. 3 fmol (7.2 pg) of an IL-1 receptor antagonist (IL-1 alpha). An antiserum a gainst substance P, but not an antiserum against somatostatin, suppressed t he 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 pa in transmission in the spinal cord at least in part by either directly or i ndirectly releasing substance P.