Recruitment of dorsal midbrain catecholaminergic pathways in the recovery from nerve injury evoked disabilities

Molecular Pain

Kevin A Keay¹  Paul J Austin¹  Hayden Houlton¹  Vignaraja Thirunavukarasu¹  Peter Wyllie¹  James W M Kang²  David Mor² 

[1] School of Medical Sciences, Discipline of Anatomy and Histology, The University of Sydney, Sydney 2006, NSW, Australia;School of Medical Sciences, Discipline of Biomedical Sciences, The University of Sydney, C42, Cumberland Campus, Lidcombe 2141, NSW, Australia

关键词: Dorsal raphe;    Dopamine;    Social behavior;    Pain;    Injury;    Sciatic nerve;    Periaqueductal gray;   

Others  :  1226129
DOI  :  10.1186/s12990-015-0049-7

 received in 2015-01-18, accepted in 2015-07-28,  发布年份 2015

【 摘 要 】

Background

The 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.

Results

Evidence 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.

Conclusions

Our 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.

【 授权许可】

   
2015 Mor et al.

【 图 表 】

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