Peripheral Nerve Injury Triggers Neuroinflammation in the Medial Prefrontal Cortex and Ventral Hippocampus in a Subgroup of Rats with Coincident Affective Behavioural Changes
Nerve damage leads to the development of disabling neuropathic pain in susceptible individuals, where patients present with pain as well as co-morbid affective behavioural disturbances, such as anhedonia, decreased motivation and depression. In this study we aimed to characterise changes in neuroinf...
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Veröffentlicht in: | Neuroscience 2019-09, Vol.416, p.147-167 |
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Sprache: | eng |
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Zusammenfassung: | Nerve damage leads to the development of disabling neuropathic pain in susceptible individuals, where patients present with pain as well as co-morbid affective behavioural disturbances, such as anhedonia, decreased motivation and depression. In this study we aimed to characterise changes in neuroinflammation in the medial prefrontal cortex (mPFC) and hippocampus (HP) in a rat model of neuropathic pain (NP) and behavioural changes. 53 rats underwent sciatic nerve chronic constriction injury (CCI) and were characterised as either, No effect, Acute effect or Lasting effect on the basis of changes in exploration behaviour in a radial-arm maze. Microglial and astrocyte morphology, as well as IL-1β, IL-6, IL-10, MCP-1, p38 MAPK and BDNF expression was quantified throughout the mPFC and HP using protein multiplex assays and immunofluorescence. All behavioural groups of CCI rats displayed equal levels of mechanical allodynia; however, the characteristic withdrawal from pellet-seeking observed in Lasting effect rats was accompanied by neuroimmune activation within the contralateral ventral HP and mPFC. This includes increased expression of IL-1β, IL-6 and MCP-1, increased phospho-p38 MAPK expression in neurons and microglia, and a shift to a reactive microglial morphology in the caudal PL and IL, ventral CA1 and DG. Therefore, neuroinflammation in the mPFC and ventral HP may influence individual differences in radial-arm maze behaviour following CCI. Our data provide further evidence that individual differences in neuroimmune activation in the interconnected ventral HP-mPFC circuitry may play a role in the divergent behavioural trajectories following nerve injury, with neuroinflammation being coincident with affective behavioural changes in susceptible individuals.
•CCI produces impaired exploratory behaviour in a subgroup of rats (Lasting effect) that is not predicted by allodynia.•These rats with ongoing behavioural change have elevated IL-1β, IL-6 and MCP-1 in the contralateral mPFC and ventral HP.•Lasting effect rats have elevated neuronal IL-6 in the contralateral caudal PL and IL, ventral pole CA1 and ventral DG.•Lasting effect rats have p38 MAPK activation in microglia and neurons within the contralateral ventral mPFC and ventral HP.•Lasting effect rats have decreased BDNF and altered astrocyte morphology in the contralateral ventral DG. |
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ISSN: | 0306-4522 1873-7544 |
DOI: | 10.1016/j.neuroscience.2019.08.005 |