Postnatal maturation of endogenous opioid systems within the periaqueductal grey and spinal dorsal horn of the rat.
Significant opioid-dependent changes occur during the fourth postnatal week in supraspinal sites (rostroventral medulla [RVM], periaqueductal grey [PAG]) that are involved in the descending control of spinal excitability via the dorsal horn (DH). Here we report developmentally regulated changes in the opioidergic signalling within the PAG and DH, which further increase our understanding of pain processing during early life. Microinjection of the μ-opioid receptor (MOR) agonist DAMGO (30 ng) into the PAG of Sprague-Dawley rats increased spinal excitability and lowered mechanical threshold to noxious stimuli in postnatal day (P)21 rats, but had inhibitory effects in adults and lacked efficacy in P10 pups. A tonic opioidergic tone within the PAG was revealed in adult rats by intra-PAG microinjection of CTOP (120 ng, MOR antagonist), which lowered mechanical thresholds and increased spinal reflex excitability. Spinal administration of DAMGO inhibited spinal excitability in all ages, yet the magnitude of this was greater in younger animals than in adults. The expression of MOR and related peptides were also investigated using TaqMan real-time polymerase chain reaction and immunohistochemistry. We found that pro-opiomelanocortin peaked at P21 in the ventral PAG, and MOR increased significantly in the DH as the animals aged. Enkephalin mRNA transcripts preceded the increase in enkephalin immunoreactive fibres in the superficial dorsal horn from P21 onwards. These results illustrate that profound differences in the endogenous opioidergic signalling system occur throughout postnatal development.
Laboratory of Developmental Nociception, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK FRAME Laboratory, Queens Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.
Charlie H T
CHT
Kwok
Ian M
IM
Devonshire
Andrew J
AJ
Bennett
Gareth J
GJ
Hathway
D000367:Age Factors; D000701:Analgesics, Opioid / Q000378:metabolism* / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology*; D006930:Hyperalgesia / Q000188:drug therapy; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D010487:Periaqueductal Gray / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism*
D000701:Analgesics, Opioid; D004745:Enkephalins; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D011333:Pro-Opiomelanocortin
Development; Dorsal horn; Neonate; Periaqueductal grey; μ-Opioid receptors