PAINSTORM Dundee Chemotherapy Induced Peripheral Neuropathy (CIPN) Study

The PAINSTORM consortium is a collaboration of leading researchers in the field of neuropathic pain (NeuP), genomics, epidemiology and neuropathy, from the UK and Belgium, and Patient Insight Partners. The Patient Insight Partners are people living with NeuP, who have been involved in the design of the study since the pre-funding stage. We are aiming to understand NeuP pathophysiology in terms of risk factors and protective mechanisms ranging from molecular pathways to social factors, and to apply this in order to improve outcomes.

As part of PAINSTORM, the University of Dundee is leading the CIPN study (PAINSTORM Dundee CIPN Study). This will involve recruitment of a cohort of people scheduled to receive potentially neurotoxic chemotherapy for cancer treatment, placing them at risk of CIPN.  This study will use longitudinal deep phenotyping (including clinical, psychosocial and psychophysical factors), with assessments from pre-chemotherapy, during and after completion of chemotherapy.  This will identify any onset and progression of neuropathy and pain, and factors that may be associated with this. Optional components of the study are blood analysis and/ or storage for potential CIPN biomarkers (e.g. neurofilament light chain) and genetic factors (storage) and up to 100 eligible participants will be sequentially offered magnetic resonance imaging (structural and functional).

NeuP is caused by a lesion or disease of the somatosensory nervous system. NeuP is common, affecting 8-10% of the population1. Crucially, not everyone with such an injury/ insult goes on to develop significant NeuP, and those who do develop it have a wide range of severity, impact, and outcomes2. This variation in pain prevalence/severity involves a complex interaction between genetic, environmental and clinical factors2,3. The exact contribution and interaction of these risk/protective factors is currently unknown, but vital to understand, so that treatment and prevention can be informed2,3. The prevalence of NeuP is projected to increase due to an aging population, the diabetes/obesity epidemic and improved cancer survival2. Unfortunately, the management of NeuP is inadequate due to poor efficacy and tolerability of current therapies. First-line therapy is usually analgesic medication, although psychological strategies and neuromodulation may be applied in specialist settings.

Cancer incidence is rising (UK:>363,000 new cases/year) and projected to increase. Combined with improved survival (50% survive for >10 years), the number of people living with cancer, and/or its treatment-related adverse effects, is also projected to increase (cancerresearchuk.org). Unfortunately, many of the commonly used and effective chemotherapies (e.g. platinums, taxanes) can cause CIPN 4. This glove-and-stocking neuropathy presents with sensory dysfunction and pain as prominent features. CIPN can affect ~67% (or more) of patients during chemotherapy; ~33% will suffer long-term problems4. It has a major impact on quality of life and can be severe enough (pain/motor function) to require dose reduction or cessation of chemotherapy, potentially reducing survival 4,5. Current treatments for established painful CIPN are usually extrapolated from other neuropathic conditions, have limited efficacy, and often have unacceptable side effects. There are no proven therapies currently available for CIPN prevention4,5. We do not fully understand why some people develop (painful) CIPN, and others do not, nor why it persists in some and not others.