Decreased PPARgamma in the trigeminal spinal subnucleus caudalis due to neonatal injury contributes to incision-induced mechanical allodynia in female rats

Abstract

Abstract Whisker pad skin incision in a neonatal rat causes prolonged mechanical allodynia after reincision in adulthood. However, sex differences in reincision-induced mechanical allodynia in the orofacial region are not fully understood. In rats that received a neonatal whisker pad incision, mechanical allodynia was significantly prolonged after adulthood reincision when compared with rats who received a neonatal sham injury. No significant sex differences were observed in the duration of mechanical allodynia. Intracisternal minocycline administration shortened the duration of mechanical allodynia in male rats but had no effect in female rats. In contrast, intracisternal administration of pioglitazone markedly suppressed mechanical allodynia in female rats after reincision. Following reincision, the number of peroxisome proliferator-activated receptor gamma (PPARγ)-positive cells was reduced in the trigeminal spinal subnucleus caudalis (Vc) in female rats that experienced neonatal injury. Immunohistochemical analyses revealed that PPARγ was predominantly expressed in Vc neurons. Pioglitazone increased the number of PPARγ-positive Vc neurons, upregulated heme oxygenase 1, and downregulated the NR1 subunit in the Vc in female rats after reincision. Together, PPARγ signaling in Vc neurons is a female-specific pathway for whisker pad skin incision-induced mechanical allodynia.