Intraventricular insulin adjacent to the arcuate nucleus reduced the formalin-induced pain through dorsal raphe nucleus opioid receptors in the STZ-induced diabetic rats

Diabetes mellitus is one of the diseases that affect nociception. In type 1 diabetes, the insulin release declines. One of the regions that respond to insulin and have insulin receptors is the hypothalamus, especially the arcuate nucleus. This hypothalamic nucleus has proopiomelanocortin (POMC)-containing neurons that affect the pain endogenous modulatory pathways such as dorsal raphe nucleus (DR) via releasing endorphins. So it was tried to investigate the influence of insulin within the arcuate nucleus with/without DR opioid receptors blockade on the nociception in the formalin test paradigm. In the present study, the role of different doses of insulin (2, 10, and 50 mIU/0.5 µl saline) within the arcuate nucleus was investigated via formalin test in type 1 (STZ-induced) diabetic rats. To perform the formalin test, 50 µl of formalin 2.5% was injected subcutaneously (s.c.) into the right palm. The behavior of the animal after the stimulation of pain receptors by s.c. formalin injection was scored from 0 (no distinguished pain) to 3 (the most nociception and highest pain score). Insulin within the arcuate nucleus diminished the nociception in formalin-induced paw in the STZ-induced diabetic rats. Intra-DR naloxone 0.2 µg/0.5 µl saline prevented this analgesia. A possible suggested mechanism for this observation is that insulin reinforces the POMC and endorphin release from the arcuate nucleus and decreases pain through DR. •Intra-arcuate nucleus insulin diminished the nociception in the type I diabetic rats.•Insulin effect was dose-dependently.•Intra-DR naloxone blocked anti-nociceptive effect of insulin.