Increased spinal prodynorphin gene expression in reinflammation-associated hyperalgesia after neonatal inflammatory insult.
BACKGROUND
Neuroplasticity induced by neonatal inflammation is the consequence of a combination of activity-dependent changes in neurons. We investigated neuronal sensitivity to a noxious stimulus in a rat model of neonatal hind-paw peripheral inflammation and assessed changes in pain behaviour at the physiological and molecular levels after peripheral reinflammation in adulthood.


RESULTS
A decrease in paw withdrawal latency (PWL) after a heat stimulus was documented in rats that received inflammatory injections in their left hind paws on postnatal day one (P1) and a reinflammation stimulus at postnatal 6-8 weeks of age, compared with normal rats. An increase in the expression of the prodynorphin (proDYN) gene was noted after reinflammation in the spinal cord ipsilateral to the afferents of the neonatally treated hind paw. The involvement of the activation of extracellular signal-regulated kinases (ERK) in peripheral inflammatory pain hypersensitivity was evidenced evident by the increase in phospho-ERK (pERK) activity after reinflammation.


CONCLUSIONS
Our results indicate that peripheral inflammation in neonates can permanently alter the pain processing pathway during the subsequent sensory stimulation of the region. Elucidation of the mechanism underlying the developing pain circuitry will provide new insights into the understanding of the early pain behaviours and the subsequent adaptation to pain.
Lin
Jack Yu-Shih
JY
Graduate Institute of Systems Biology and Bioinformatics, National Central University, Chungli, Taiwan.
Cheng
Yu-Che
YC
Chen
Julia Yi-Ru
JY
Chien
Chih-Cheng
CC
Lin
Shih-Chang
SC
Wen
Yeong-Ray
YR
Tsou
Tsung-Shan
TS
Ling
Qing-Dong
QD
D000818:Animals; D000831:Animals, Newborn; D004195:Disease Models, Animal; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation / Q000502:physiology*; D006614:Hindlimb; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010812:Physical Stimulation / Q000379:methods; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics*
D004745:Enkephalins; D011498:Protein Precursors; C033660:preproenkephalin