Background and Objective: Recent reports have implicated inflammation in morphine tolerance. However, its mechanisms and site of action in the brain remain to be understood. We aim to examine changes in the expression of some long non-coding RNAs (lncRNAs), inflammatory cytokines and their receptors in the hypothalamus in morphine-tolerant rats. Materials and Methods: Two groups of male Wistar rats received saline (1 ml/kg) or morphine (10 mg/kg) twice daily for 8 consecutive days. A hotplate test of analgesia was used to assess the induction of morphine analgesic tolerance on day 8 of the schedule. On day 8 of the treatments, each rat was anesthetized, decapitated and the hypothalamus was dissected on an ice-chilled surface. The gene expression of TNF, IL1, IL6 and their receptors, as well as MIAT1 and BC1 long-non-coding RNAs were examined using a real-time quantitative polymerase chain reaction (qPCR) method. Results: The hotplate test revealed that the 8 days morphine treatments induced anti-nociceptive tolerance to the opioid. The qPCR results indicated that the MIAT1 and BC1 lncRNAs expression and also the gene expression of TNF, IL1 and their receptors were increased but IL6 remained with no significant changes in the hypothalamus of morphine-tolerant group compared to the saline-treated group. Conclusion: It can be concluded that the increases in the lncRNAs expression affects the expression inflammatory cytokines and their receptors in the hypothalamus, which may underlie, at least partly, the neuroinflammation and the decreases in morphine-induced analgesia after repeated use of the opioid.
