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Targeting neuroinflammation to combat pathological pain in neurodegenerative diseases and chronic pain syndromes

Periodic Reporting for period 1 - TOBeATPAIN (Targeting neuroinflammation to combat pathological pain in neurodegenerative diseases and chronic pain syndromes)

Reporting period: 2018-08-01 to 2020-07-31

TOBeATPAIN partners and ESRs have not started to publish their work. However, KCL partners have acknowledged the ITN in four review articles on pain in Parkinson’s disease; the role of the immune system in neuropathic pain and the translational value of preclinical models for rheumatoid arthritis pain.Chronic pain contributes, with an ageing population, to increased EU health and social care costs. A better management of chronic pain conditions, which would improve the quality of life of European citizens, is dependent on more studies that address the mechanisms of pathological pain and identification of novel targets for pain relief. Currently available painkillers for chronic pain conditions are partially effective and leave a third of pain sufferers untreated. Antidepressants, anti-epileptic drugs and opioids are used for neuropathic pain relief with varying levels of success. NSAIDs are the main class of analgesics used in rheumatoid arthritis people. Paracetamol is used as analgesic medication to address pain in people with dementia. However, over-the-counter analgesics are associated with severe side effects, which limit their application in neurodegeneration disease patients. TOBeATPAIN proposes that our investigation into mechanisms of neuroinflammation in CNS and PNS will offer innovative, non-neuronal targets for pathological pain treatment.

The aim of TOBeATPAIN research is to investigate the underlying mechanisms of chronic pain with a specific focus on neuro-immune interactions in neurodegenerative diseases associated with pathological pain (workpackage [WP]1), rheumatic diseases (WP2) and peripheral neuropathies (WP3). We have recruited 11 Early Stage Researchers (ESRs) who have begun to address the research objectives (RO) associated with each WP, which are as follows:

• RO1: Pathophysiology of pain in Alzheimer’s disease and Parkinson’s disease which are characterised by neuroinflammation
• RO2: Pathophysiology of neuroinflammation in fibromyalgia and rheumatoid arthritis pain
• RO3: Pathophysiology of neuroinflammation in painful peripheral neuropathies
We use rodent models of Alzheimer’s disease (AD) in which we have observed that the development of chronic pain associated with systemic inflammation is altered alongside changes in AD brain pathology and associated neuroinflammation.

In rodent models of Parkinson’s disease (PD), we have observed the development of pain-like behaviour that resembles pain observed in patients with PD. We are investigating the involvement of neuroinflammation in the brain in pain-like behaviour.

In models of fibromyalgia (FM) and rheumatoid arthritis (RA) we have observed changes in immune cells that are in the vicinity of pain neurons and we are evaluating their potential role in pain-like behaviour with special attention to pro-inflammatory factors. In patients with fibromyalgia we are investigating possible changes in the ability to modulate pain perception. In a mouse model of Fabry disease (FD) we have observed the development of neuroinflammation in the brain and we are investigating the effect of new compounds as analgesics in FD and other peripheral neuropathies (PN) associated with pain
AD: Improved pain control of patients with AD to reduce the impact that chronic pain has on psychiatric symptoms. Thus, identification of targets for pain treatment would reduce societal costs and would improve patients’ quality of life.
PD: In 2015, an estimated 127,000 people in the UK were living with Parkinson’s disease - 6.2 million worldwide – and up to 80% of these patients are affected by pain. Of these approximately half gain no relief with current analgesics, there is a clear unmet medical need for better pain relief for people with Parkinson’s. The impact of this project on society will ultimately depend on the outcome of any subsequent clinical trials with analgesics borne out of the work conducted through TOBeATPAIN. If an effective analgesic is identified, this would have significant positive impact on enhancing the quality of life of people living with PD Ultimately, obtained results could be considered by pharmaceutical companies in order to develop novel treatments for pain in PD or to improve existing ones.
FM and RA: The impact of this project is likely to be broadening our knowledge on immune mechanisms contributing to pain. Depending on the data this knowledge may contribute to the development of new products and in that way have a more direct impact on our society.
FD and PN: This project will advance our knowledge of Fabry disease and help with clinical treatment of pain and CNS-related symptoms. The elucidation of the active principle of medical marijuana bioactive substances is expected to have a positive impact on the social acceptance of medical marijuana as a therapeutic agent. The quality of life of patients, who could benefit from the use of medical marijuana pharmaceuticals, could significantly increase.
The potential impact of TOBeATPAIN findings on society would be disseminated in the following ways: i) publication of acquired outcomes in scientific journals; ii) use of the results for lectures; iii) dissemination of the results to scientists and clinicians during participation in conferences and meetings; iv) discussion fora held with patient groups.
TOBeATPAIN Impact
TOBeATPAIN Project Logo designed by Andrea Ebersberger UKJ