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Postnatal maturation of endogenous opioid systems within the periaqueductal grey and spinal dorsal horn of the rat

Bennett, Andrew; Kwok, Charlie H.T.; Devonshire, Ian M.; Hathway, Gareth J.


Charlie H.T. Kwok

Ian M. Devonshire


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 adminstration 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.


Bennett, A., Kwok, C. H., Devonshire, I. M., & Hathway, G. J. (2014). Postnatal maturation of endogenous opioid systems within the periaqueductal grey and spinal dorsal horn of the rat. PAIN, 155(1), 168-178.

Journal Article Type Article
Acceptance Date Sep 20, 2013
Publication Date Jan 1, 2014
Deposit Date Mar 7, 2018
Print ISSN 0304-3959
Publisher Lippincott, Williams & Wilkins
Peer Reviewed Peer Reviewed
Volume 155
Issue 1
Pages 168-178
Public URL
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