Future efforts could be directed to verifying the roles of these pathways HIF-1α, leptin/TNF/RIPK and estradiol/cadherin-11in mediating the HFD-induced aggravation of IP, in addition to studying how HFD increases the activity of these pathways, and whether iNOS mediates the aggravated pain in other time points in HFD-fed animals. Here, NOS2 is linked to incontinentia pigmenti.