Intracerebroventricular saline treatment elevates the pain threshold. Is this phenomenon mediated by peripheral opiate receptors?

Intracerebroventricular (i.c.v.) saline treatment of unanaesthetized mice resulted in moderate but well detectable analgesia. This elevation of pain threshold (by 60-90%) could be observed already 2 min after i.c.v. injection and lasted 15-30 min. Surprisingly, the analgesic action of i.c.v. treatment was not attenuated if naloxone was administered i.c.v. instead of saline. In fact if applying it in higher doses, the opiate antagonist potentiated the antinociceptive action. However, giving naloxone subcutaneously (s.c.) before i.c.v. saline treatment, the resulting analgesia was significantly reduced. It is tentatively put forward that i.c.v. treatment is stressful and in itself may induce mobilization of endogenous opioids and the latters elevate the pain threshold via peripheral opiate mechanisms.