NADPH-d/NOS reactivity in the lumbar dorsal horn of congenitally hypothyroid pups before and after formalin pain induction

We have previously demonstrated that congenitally hypothyroid rat pups exhibit altered behavioral response to formalin pain induction during postnatal period. In the present study, using NADPH-diaphorase histochemistry and NOS immunostaining, we investigated the effect of congenital hypothyroidism on the NOS expression in spinal cord of intact neonates at postnatal days of 15 and 21. We also examined the effect of thyroid dysfunction on the NADPH-d/NOS expression in response to formalin nociception. Congenital hypothyroidism induced by propylthiouracil (PTU) treatment started from gestational day 16 and continued to postnatal day 15 or 21. Congenitally hypothyroid pups exhibited marked reduction in NADPH-d reactive cells (84% and 66% in P15 and P21, respectively; P < 0.001) and NOS-ir cells (52% and 91% in P15 and P21, respectively; P < 0.001) in superficial lumbar dorsal horn laminae (I–II) as compared to that of normal pups. Moreover, in congenitally hypothyroid pups the NADPH-d/NOS expression following hindpaw formalin injection did not change significantly. Our results demonstrate that congenital hypothyroidism affect developmental expression of NOS in spinal dorsal horn, which may in part explain the altered behavioral pain response as we previously reported in hypothyroid pups.