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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

Levels of dominance behaviour before and after nerve injury. Top panel mean durations (in seconds) of dominance behaviour (±SEM) measured: pre-injury (days 3–5); days 1–3 post-injury and; days 4–6 post-injury in behavioural controls, sham surgery rats and rats with Pain alone, Pain and Disability and Pain and Transient Disability. Significance with respect to pre-injury days is shown ***p < 0.001 (ANOVA, and post hoc Fischer’s PLSD). Lower panel individual data for Pain alone, Pain and Disability and Pain and Transient Disability post-CCI behavioural groups. Data are expressed as the mean percentage change from pre-CCI levels for days 1–3 post-CCI and days 4–6 post-CCI. The shaded area indicates a 30% reduction from pre-injury dominance behaviours. Rats that showed no differences in their post-CCI dominance behaviour were defined as Pain alone rats. Rats with a decrease of at least 30% in the duration of their dominance behaviours on 4 or more of the 6 days post injury days were defined as Pain and Disability rats. The rats that showed a 30% or more reduction in their dominance behaviours for days 1–3 post-CCI but then returned to pre-CCI levels were considered Pain and Transient Disability rats.
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Fig1: Levels of dominance behaviour before and after nerve injury. Top panel mean durations (in seconds) of dominance behaviour (±SEM) measured: pre-injury (days 3–5); days 1–3 post-injury and; days 4–6 post-injury in behavioural controls, sham surgery rats and rats with Pain alone, Pain and Disability and Pain and Transient Disability. Significance with respect to pre-injury days is shown ***p < 0.001 (ANOVA, and post hoc Fischer’s PLSD). Lower panel individual data for Pain alone, Pain and Disability and Pain and Transient Disability post-CCI behavioural groups. Data are expressed as the mean percentage change from pre-CCI levels for days 1–3 post-CCI and days 4–6 post-CCI. The shaded area indicates a 30% reduction from pre-injury dominance behaviours. Rats that showed no differences in their post-CCI dominance behaviour were defined as Pain alone rats. Rats with a decrease of at least 30% in the duration of their dominance behaviours on 4 or more of the 6 days post injury days were defined as Pain and Disability rats. The rats that showed a 30% or more reduction in their dominance behaviours for days 1–3 post-CCI but then returned to pre-CCI levels were considered Pain and Transient Disability rats.

Mentions: Replicating our previous findings, rats could be categorised into three groups post-CCI based upon changes in their dominance and non-social behaviours in the resident-intruder, social interactions test [14, 19–21]. Of the 55 rats that underwent CCI and daily resident-intruder testing, fifty-four percent (30/55) were classified as Pain alone, as their dominance behaviours in response to the presence of an intruder did not decrease significantly following nerve injury. Twenty-seven percent (15/55) showed persistent reductions in dominance levels following the injury and were classified as Pain and Disability rats. Nineteen percent (10/55) rats showed a transient reduction in dominance levels in the first 2–3 days following injury but returned to pre-injury levels during days 4–6 and were classified as Pain andTransient Disability rats. These findings are summarised in Fig. 1.Fig. 1


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)

Levels of dominance behaviour before and after nerve injury. Top panel mean durations (in seconds) of dominance behaviour (±SEM) measured: pre-injury (days 3–5); days 1–3 post-injury and; days 4–6 post-injury in behavioural controls, sham surgery rats and rats with Pain alone, Pain and Disability and Pain and Transient Disability. Significance with respect to pre-injury days is shown ***p < 0.001 (ANOVA, and post hoc Fischer’s PLSD). Lower panel individual data for Pain alone, Pain and Disability and Pain and Transient Disability post-CCI behavioural groups. Data are expressed as the mean percentage change from pre-CCI levels for days 1–3 post-CCI and days 4–6 post-CCI. The shaded area indicates a 30% reduction from pre-injury dominance behaviours. Rats that showed no differences in their post-CCI dominance behaviour were defined as Pain alone rats. Rats with a decrease of at least 30% in the duration of their dominance behaviours on 4 or more of the 6 days post injury days were defined as Pain and Disability rats. The rats that showed a 30% or more reduction in their dominance behaviours for days 1–3 post-CCI but then returned to pre-CCI levels were considered Pain and Transient Disability rats.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: Levels of dominance behaviour before and after nerve injury. Top panel mean durations (in seconds) of dominance behaviour (±SEM) measured: pre-injury (days 3–5); days 1–3 post-injury and; days 4–6 post-injury in behavioural controls, sham surgery rats and rats with Pain alone, Pain and Disability and Pain and Transient Disability. Significance with respect to pre-injury days is shown ***p < 0.001 (ANOVA, and post hoc Fischer’s PLSD). Lower panel individual data for Pain alone, Pain and Disability and Pain and Transient Disability post-CCI behavioural groups. Data are expressed as the mean percentage change from pre-CCI levels for days 1–3 post-CCI and days 4–6 post-CCI. The shaded area indicates a 30% reduction from pre-injury dominance behaviours. Rats that showed no differences in their post-CCI dominance behaviour were defined as Pain alone rats. Rats with a decrease of at least 30% in the duration of their dominance behaviours on 4 or more of the 6 days post injury days were defined as Pain and Disability rats. The rats that showed a 30% or more reduction in their dominance behaviours for days 1–3 post-CCI but then returned to pre-CCI levels were considered Pain and Transient Disability rats.
Mentions: Replicating our previous findings, rats could be categorised into three groups post-CCI based upon changes in their dominance and non-social behaviours in the resident-intruder, social interactions test [14, 19–21]. Of the 55 rats that underwent CCI and daily resident-intruder testing, fifty-four percent (30/55) were classified as Pain alone, as their dominance behaviours in response to the presence of an intruder did not decrease significantly following nerve injury. Twenty-seven percent (15/55) showed persistent reductions in dominance levels following the injury and were classified as Pain and Disability rats. Nineteen percent (10/55) rats showed a transient reduction in dominance levels in the first 2–3 days following injury but returned to pre-injury levels during days 4–6 and were classified as Pain andTransient Disability rats. These findings are summarised in Fig. 1.Fig. 1

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