Research Question: Can responders to botulinum toxin, serotype A (BoNT/A) be identified among chronic neuropathic pain patients prior to treatment based on a genetic signature?
Aims: Identify a genetic biomarker to predict which chronic pain patients will likely respond to BoNT/A, avoiding ineffective treatments for non-responders.
Objectives
1. Identify UKB individuals treated with BoNT/A for peripheral neuropathic pain.
2. Determine the number of treatments received.
3. Identify non-responders (stopped after a few injections) and responders (received at least four treatments).
4. Select sufficiently powered groups of responders and non-responders.
5. Retrieve and analyze genetic data of responders and non-responders.
6. Use promising genetic markers for patient stratification in clinical trials and evaluate their predictive value.
Scientific Rationale: Botulinum toxin, particularly Botulinum toxin type A (BoNT/A), has emerged as a promising treatment for peripheral chronic pain. The analgesic mode of action of BoNT/A is not completely understood but likely involves the following processes. Blocking the release of neurotransmitters involved in pain signaling (e.g. substance P, calcitonin gene-related peptide, glutamate) and reduction of pain generating signal transmission to spinal cord and brain. It also reduces the expression of TRPV1 receptors, a validated target in chronic pain.
BoNT/A has shown significant clinical efficacy in reducing intensity of peripheral neuropathic pain, though not all patients respond. Identifying genetic markers in the group of responders could improve treatment strategies. For the development of clinically relevant biomarker assays that apply to larger and diverse patient groups, identification of genetic variations in a large population of chronic pain patients is required.
