Dynorphin (DYN), an opioid peptide, plays an important role in the neural circuitry of nociception. DYN mRNA is expressed at a low constitutive level in dorsal horn neurons. Following noxious stimulation of the periphery, there is a dramatic induction in DYN mMRNA. We have used changes in DYN mRNA expression as an indicator of activity in spinal pain pathways. The aging process is associated with physiological and behavioral changes that may influence neuronal processing of noxious inputs. Genetic differences in rat strains may also impact the molecular response to noxious stimulation. This study examined the impact of rat strain and age on the behavioral response and regulation of spinal DYN mRNA after peripheral inflammation. F344 rats developed greater inflammation, hyperalgesia and DYN induction than SD and LEW rats. These results indicate that both genetic factors and aging have roles in the response to peripheral inflammation and hyperalgesia. Spinal nociceptive neural circuits undergo considerable postnatal (P) changes. This study compares neonatal and adult response to noxious inputs. At P9 there was induction of spinal DYN at near peak levels by 8 hrs which was significantly reduced by day 3. In contrast, in adult rats DYN reached peak levels at day 1 and persisted at high levels through day 3. These data demonstrate a robust inflammation induced hyperalgesia in neonates and a corresponding dramatic response in spinal nociceptive neuronal circuits that occurs faster than seen in the adult. These data stress the importance of pain control in neonates. Glucocorticoids (GC) function peripherally to suppress inflammation by acting on the inflammatory/immune response and centrally at neuronal steroid receptors to modify gene expression. Adrenalectomized (ADX) rats with steroid receptors to modify gene expression. Adrenalectomized (ADX) rats with, and without, GC replacement were compared to normal (N) an sham (SH) surgery rats. ADX markedly increase the induction of DYN mRNA related to inflammation and hyperalgesia. GC replacement reversed the DYN enhancement. These data demonstrate profound effects of GC on both the peripheral and central response to inflammation and hyperalgesia.
