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The molecular and cellular basis of structural plasticity and reorganisation in chronic pain

The molecular and cellular basis of structural plasticity and reorganisation in chronic pain

Objective

Chronic pain is a serious medical problem and a socioeconomic burden that severely reduces quality of life worldwide. Neural plasticity constitutes a key element of pathological pain, which can come about over various anatomical and temporal scales. Apart from functional plasticity, tremendous potential exists for changes in the structure, connectivity and representation of pain, which can account for long-term persistence of pathological pain. This grant aims to study structural plasticity processes in the somatosensory nociceptive system, test their functional significance and address underlying molecular and cellular mechanisms, a topic not adequately studied so far owing to technical constraints.
On the background of our established repertoire of mouse models for chronic pain and transgenic/viral gene delivery/RNA interference approaches for molecular manipulations, two key complementary methodologies will be employed to visualize and modify structural plasticity, namely non-invasive multiphoton in vivo imaging and optogenetic reversible modulation of neuronal activity in vivo, respectively. We will dynamically study sprouting, regeneration and rewiring of sensory nerves over the progression of neuropathic and tumor-evoked pain and image invasion of tumor cells into nerves. Moreover, we will directly image remodelling of synaptic contacts in brain regions processing pain. Importantly, the impact of structural changes on function will be studied by measuring pain behavior concurrently in the same animals and via targeted molecular interventions. Secondly, optogenetic activation and reversible silencing of nociceptors or specific areas in the brain in vivo will be used to directly measure peripheral and central contributions to plasticity and chronic pain behavior.
These innovative, multidisciplinary approaches promise to deliver important novel insights into mechanisms driving chronic pain and provide a basis for new ways of reversing pathological processes.
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Principal Investigator

Rohini Kuner (Prof.)

Host institution

UNIVERSITATSKLINIKUM HEIDELBERG

Address

Im Neuenheimer Feld 672
69120 Heidelberg

Germany

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 1 992 000

Principal Investigator

Rohini Kuner (Prof.)

Administrative Contact

Thorsten Brietz (Mr.)

Beneficiaries (1)

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UNIVERSITATSKLINIKUM HEIDELBERG

Germany

EU Contribution

€ 1 992 000

Project information

Grant agreement ID: 294293

Status

Closed project

  • Start date

    1 July 2012

  • End date

    30 June 2018

Funded under:

FP7-IDEAS-ERC

  • Overall budget:

    € 1 992 000

  • EU contribution

    € 1 992 000

Hosted by:

UNIVERSITATSKLINIKUM HEIDELBERG

Germany