The Involvement of Enkephalin System in Analgesia Induced by Brain Iron Deficiency

Iron deficiency (ID) induces in rats marked reduction of brain iron and dopamine D2 receptor. The resultant effects are a wide variety of changes in dopamine-mediated behaviors including thermo-regulation, motor activity, stereotyped behavior and diminished learning. Another behavioral change resulting from ID rats is an increase in the pain threshold, which is dependent on the duration and severity of ID. The results showed that peripheral administration of enkaphalines (0.1-3.0 mg/kg I.P.) potentiates ID-induced analgesia and causes a higher pain threshold, a phenomenon not observed in control rats.This effect may be associated with the known functional alteration in blood brain barrier resulting from ID. The opiate antagonists, naloxone (2 mg/kg and MIF-I (1 mg/kg), blocked the opiate-induced pain threshold potentiation in ID. Furthermore, the levels of dynorphin B and met-enkephalin are significantly increased in dopamine opiate-rich brain areas (caudate nucleus, substantia nigra, nucleus accumbens and globus pallidus) during ID. These phenomena can be reversed by placing rats on iron plus (control) diet for 24 days. It is concluded that a decrease in brain dopamine neurotransmission is associated with an increased functional level of the opiate system and that this mechanism mediates not only the analgesic effect but may also be associated with learning deficit observed in ID rats.