Role of the spinal cord in intracisternal β-endorphin-evoked suppression of liver DNA synthesis in 10-day-old rats

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Previously, we have shown that intracisternal (i.c.) administration of β-endorphin (an opioid peptide naturally occurring in the brain) to preweanling rats markedly decreases DNA synthesis (an index of cell proliferation) in both brain and liver. This observation is consistent with our hypothesis that endogenous CNS β-endorphin plays an important role in controlling postnatal growth. The current research specifically undertook to investigate, in 10-day-old rats, whether or not i.c. β-endorphin-evoked suppression of liver DNA synthesis is actually mediated by spinal opioid receptors and/or by descending endorphinergic pathways. In contrast to the i.c. route of administration, β-endorphin given directly into the spinal subarachnoid space via intrathecal (i.t.) injection did not alter liver DNA synthesis, yet was able to evoke profound antinociceptive responses. This demonstrates that intracisternally applied β-endorphin exerts its effect on liver DNA by acting at supraspinal sites, and not by directly stimulating spinal opioid receptors after diffusion from its intracerebral site of injection. As it is possible that β-endorphin's supraspinal actions may activate a descending inhibitory endorphinergic pathway to reduce DNA synthesis, we conducted studies in rat pups administered naloxone intrathecally. Naloxone i.t. was completely ineffective in preventing β-endorphin i.c. from inhibiting liver DNA synthesis. On the other hand, i.t. coinjection of naloxone plus β-endorphin was able to block the analgesic response, while their i.c. coinjection reversed the DNA effect. The results from these studies indicate that opioid systems within the spinal cord do not play a major role in mediating CNS β-endorphin's regulation of DNA synthesis in peripheral tissues. However, the data obtained do not necessarily exclude other spinal neurochemical systems (e.g. adrenergic or serotonergic) from participating in this process.