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

Mor D, Kang JW, Wyllie P, Thirunavukarasu V, Houlton H, Austin PJ, Keay KA - Mol Pain (2015)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Medical Sciences, Discipline of Biomedical Sciences, The University of Sydney, C42, Cumberland Campus, Lidcombe, NSW, 2141, Australia. david.mor@sydney.edu.au.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus

TH-expression in the vPAG of rats with distinct patterns of injury-triggered disability. Top rowa–d shows photomicrographs of TH immunoreactivity in the vPAG under brightfield illumination. a −6.3 mm caudal to bregma; b −6.8 mm caudal to bregma; c, −7.3 mm caudal to bregma; and d −7.8 mm caudal to bregma. The scale bar represent 1.0 mm. Directly below each photomicrograph, box and whisker plots illustrate (1) the mean number (±SEM) of TH-IR cells; (2) the mean intensity (±SEM) of staining in TH-IR neurons and; (3) the mean density (±SEM) of TH-IR fibers, at each of these rostro-caudal levels of the vPAG in five rats from each of the behaviourally characterized groups. Significant differences between behavioural groups is shown *p < 0.05 (2-way ANOVA, Bonferroni test).
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Fig3: TH-expression in the vPAG of rats with distinct patterns of injury-triggered disability. Top rowa–d shows photomicrographs of TH immunoreactivity in the vPAG under brightfield illumination. a −6.3 mm caudal to bregma; b −6.8 mm caudal to bregma; c, −7.3 mm caudal to bregma; and d −7.8 mm caudal to bregma. The scale bar represent 1.0 mm. Directly below each photomicrograph, box and whisker plots illustrate (1) the mean number (±SEM) of TH-IR cells; (2) the mean intensity (±SEM) of staining in TH-IR neurons and; (3) the mean density (±SEM) of TH-IR fibers, at each of these rostro-caudal levels of the vPAG in five rats from each of the behaviourally characterized groups. Significant differences between behavioural groups is shown *p < 0.05 (2-way ANOVA, Bonferroni test).

Mentions: In injured rats, TH-IR cells and fibers were observed in midbrain sections under the light microscope. TH-IR cell profiles were found in the intermediate lateral PAG; the ventrolateral PAG and the DRN (Fig. 3, top row). In all rats evaluated the largest numbers of TH-IR cells were found in the DRN at approximately −7.3 mm from bregma (Fig. 3, second row, column c). However these cell numbers did not differ between groups. TH-IR in the neurons of rats with Pain and Transient Disability was significantly greater than that in Pain alone rats at −7.3 mm from bregma (F11,48 = 5.443, p < 0.05) (Fig. 3, third row, column c). Further, rats with Pain andTransient Disability also showed increased densities of TH-IR fibers at 7.3 and 7.8 mm caudal to bregma, compared to both Pain and Disability and Pain alone rats (F11,48 = 19.97, p < 0.001) (Fig. 3, fourth row, columns c, d).Fig. 3


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

Mor D, Kang JW, Wyllie P, Thirunavukarasu V, Houlton H, Austin PJ, Keay KA - Mol Pain (2015)

TH-expression in the vPAG of rats with distinct patterns of injury-triggered disability. Top rowa–d shows photomicrographs of TH immunoreactivity in the vPAG under brightfield illumination. a −6.3 mm caudal to bregma; b −6.8 mm caudal to bregma; c, −7.3 mm caudal to bregma; and d −7.8 mm caudal to bregma. The scale bar represent 1.0 mm. Directly below each photomicrograph, box and whisker plots illustrate (1) the mean number (±SEM) of TH-IR cells; (2) the mean intensity (±SEM) of staining in TH-IR neurons and; (3) the mean density (±SEM) of TH-IR fibers, at each of these rostro-caudal levels of the vPAG in five rats from each of the behaviourally characterized groups. Significant differences between behavioural groups is shown *p < 0.05 (2-way ANOVA, Bonferroni test).
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4538917&req=5

Fig3: TH-expression in the vPAG of rats with distinct patterns of injury-triggered disability. Top rowa–d shows photomicrographs of TH immunoreactivity in the vPAG under brightfield illumination. a −6.3 mm caudal to bregma; b −6.8 mm caudal to bregma; c, −7.3 mm caudal to bregma; and d −7.8 mm caudal to bregma. The scale bar represent 1.0 mm. Directly below each photomicrograph, box and whisker plots illustrate (1) the mean number (±SEM) of TH-IR cells; (2) the mean intensity (±SEM) of staining in TH-IR neurons and; (3) the mean density (±SEM) of TH-IR fibers, at each of these rostro-caudal levels of the vPAG in five rats from each of the behaviourally characterized groups. Significant differences between behavioural groups is shown *p < 0.05 (2-way ANOVA, Bonferroni test).
Mentions: In injured rats, TH-IR cells and fibers were observed in midbrain sections under the light microscope. TH-IR cell profiles were found in the intermediate lateral PAG; the ventrolateral PAG and the DRN (Fig. 3, top row). In all rats evaluated the largest numbers of TH-IR cells were found in the DRN at approximately −7.3 mm from bregma (Fig. 3, second row, column c). However these cell numbers did not differ between groups. TH-IR in the neurons of rats with Pain and Transient Disability was significantly greater than that in Pain alone rats at −7.3 mm from bregma (F11,48 = 5.443, p < 0.05) (Fig. 3, third row, column c). Further, rats with Pain andTransient Disability also showed increased densities of TH-IR fibers at 7.3 and 7.8 mm caudal to bregma, compared to both Pain and Disability and Pain alone rats (F11,48 = 19.97, p < 0.001) (Fig. 3, fourth row, columns c, d).Fig. 3

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: School of Medical Sciences, Discipline of Biomedical Sciences, The University of Sydney, C42, Cumberland Campus, Lidcombe, NSW, 2141, Australia. david.mor@sydney.edu.au.

ABSTRACT

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.

No MeSH data available.


Related in: MedlinePlus