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Molecular Pain

, 11:50

First Online: 18 August 2015Received: 18 January 2015Accepted: 28 July 2015


BackgroundThe periaqueductal gray region PAG is one of several brain areas identified to be vulnerable to structural and functional change following peripheral nerve injury. Sciatic nerve constriction injury CCI triggers neuropathic pain and three distinct profiles of changes in complex behaviours, which include altered social and sleep–wake behaviours as well as changes in endocrine function. The PAG encompasses subgroups of the A10 dopaminergic and A6 noradrenergic cell groups; the origins of significant ascending projections to hypothalamic and forebrain regions, which regulate sleep, complex behaviours and endocrine function. We used RT-PCR, western blots and immunohistochemistry for tyrosine hydroxylase to determine whether 1 tyrosine hydroxylase increased in the A10-A6 cells and-or; 2 de novo synthesis of tyrosine hydroxylase, in a ‘TH-naïve’ population of ventral PAG neurons characterized rats with distinct patterns of behavioural and endocrine change co-morbid with CCI evoked-pain.

ResultsEvidence for increased tyrosine hydroxylase transcription and translation in the constitutive A10-A6 cells was found in the midbrain of rats that showed an initial 2–3 day post-CCI, behavioural and endocrine change, which recovered by days 5–6 post-CCI. Furthermore these rats showed significant increases in the density of TH-IR fibres in the vPAG.

ConclusionsOur data provide evidence for: 1 potential increases in dopamine and noradrenaline synthesis in vPAG cells; and 2 increased catecholaminergic drive on vPAG neurons in rats in which transient changes in social behavior are seen following CCI. The data suggests a role for dopaminergic and noradrenergic outputs, and catecholaminergic inputs of the vPAG in the expression of one of the profiles of behavioural and endocrine change triggered by nerve injury.

KeywordsPeriaqueductal gray Sciatic nerve Injury Pain Social behavior Dopamine Dorsal raphe AbbreviationsDAdopamine

DRNdorsal raphe nucleus

CCIchronic constriction injury

lPAGlateral periaqueductal grey column

mPFCmedial prefrontal cortex

NAcnucleus accumbens

PAGperiaqueductal grey

SWSslow wave sleep

RT-PCRreverse transcription polymerase chain reaction

THtyrosine hydroxylase

TH-IRtyrosine hydroxylase immunoreactive

vPAGventral periaqueductal grey region

VTAventral tegmental area

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Autor: David Mor - James W M Kang - Peter Wyllie - Vignaraja Thirunavukarasu - Hayden Houlton - Paul J Austin - Kevin A Keay


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