Vitamin A active metabolite, all-trans retinoic acid, induces spinal cord sensitization. II. Effects after intrathecal administration.
OBJECTIVE
In our previous study (see accompanying paper) we observed that all-trans retinoic acid (ATRA) p.o. induces changes in spinal cord neuronal responses similar to those observed in inflammation-induced sensitization. In the present study we assessed the it. effects of ATRA, and its mechanisms of action.


METHODS
The effects of all drugs were studied after it. administration in nociceptive withdrawal reflexes using behavioural tests in awake male Wistar rats.


RESULTS
The administration of ATRA in normal rats induced a dose-dependent enhancement of nociceptive responses to noxious mechanical and thermal stimulation, as well as responses to innocuous stimulation. The intensity of the responses was similar to that observed in non-treated animals after carrageenan-induced inflammation. The effect induced by ATRA was fully prevented by the previous administration of the retinoic acid receptor (RAR) pan-antagonist LE540 but not by the retinoid X receptor (RXR) pan-antagonist HX531, suggesting a selective action on spinal cord RARs. The COX inhibitor dexketoprofen and the interleukin-1 receptor antagonist IL-1ra inhibited ATRA effect. The results indicate that COX and interleukin-1 are involved in the effects of ATRA in the spinal cord, similar to that seen in inflammation.


CONCLUSIONS
In conclusion, ATRA induces changes in the spinal cord similar to those observed in inflammation. The sensitization-like effect induced by ATRA was mediated by RARs and associated with a modulation of COX-2 and interleukin-1 activities. ATRA might be involved in the mechanisms underlying the initiation and/or maintenance of sensitization in the spinal cord.
Alique
M
M
Facultad de Medicina, Departamento de Fisiología, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain.
Lucio
F J
FJ
Herrero
J F
JF
D000818:Animals; D003984:Dibenzazepines / Q000494:pharmacology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced; D007278:Injections, Spinal; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D010147:Pain Measurement / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017208:Rats, Wistar; D018168:Receptors, Retinoic Acid / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects*; D014212:Tretinoin / Q000008:administration & dosage* / Q000494:pharmacology*
D003984:Dibenzazepines; D007375:Interleukin-1; C104183:LE 540; D018168:Receptors, Retinoic Acid; D014212:Tretinoin