Central effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity.
To extend the knowledge on the central effects of cytokines, we studied the effects of tumor necrosis factor alpha and interleukin-1 alpha on nociceptive thresholds and spontaneous locomotor activity in rats. After central administration, both tumor necrosis factor alpha and interleukin-1 alpha significantly (P < 0.001) increase the nociceptive thresholds as measured by the hot-plate test. Tumor necrosis factor alpha, but not interleukin-1 alpha decreases spontaneous locomotor activity evaluated by the Animex test. The increase in nociceptive thresholds induced by tumor necrosis factor alpha or interleukin-1 alpha is not affected by the opiate receptor antagonist naloxone, or antisera against the endogenous opioids beta-endorphin, met-enkephalin or dynorphin. The analgesic effect of tumor necrosis factor alpha is completely antagonized by anti-IL-1 antibodies. Moreover, the cyclooxygenase inhibitor indomethacin does not antagonize the increase of nociceptive thresholds induced by either cytokine.
Bianchi
M
M
Department of Pharmacology, School of Medicine, University of Milano, Italy.
Sacerdote
P
P
Ricciardi-Castagnoli
P
P
Mantegazza
P
P
Panerai
A E
AE
D000698:Analgesia; D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003429:Cross Reactions; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010146:Pain / Q000503:physiopathology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012684:Sensory Thresholds / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology*; D001615:beta-Endorphin / Q000032:analysis / Q000378:metabolism; D008083:beta-Lipotropin / Q000032:analysis / Q000378:metabolism
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D001615:beta-Endorphin; D008083:beta-Lipotropin