BDNF as a biomarker for neuropathic pain: Consideration of mechanisms of action and associated measurement challenges

• Published in: Brain and behavior Vol. 13; no. 3; pp. e2903 - n/a
• Main Authors: Thakkar, Bhushan, Acevedo, Edmund O.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-03-2023; John Wiley and Sons Inc; Wiley
• Subjects: Animals; BDNF; biomarker; Biomarkers; Brain-Derived Neurotrophic Factor; Central Nervous System; Chronic Pain; Endometriosis; Fibromyalgia; Humans; measurement; Measurement techniques; mechanisms; Nervous system; Neuralgia - diagnosis; neuropathic pain; Ovaries; Physiology; Plasma; Quality of life; Review; Schizophrenia; Spinal cord; Temporomandibular joint disorders; Tumors; neuropathic pain; biomarker; BDNF; mechanisms; measurement
• ISSN: 2162-3279; 2162-3279
• DOI: 10.1002/brb3.2903

Introduction
The primary objective of this paper is to (1) provide a summary of human studies that have used brain derived neurotrophic factor (BDNF) as a biomarker, (2) review animal studies that help to elucidate the mechanistic involvement of BDNF in the development and maintenance of neuropathic pain (NP), and (3) provide a critique of the existing measurement techniques to highlight the limitations of the methods utilized to quantify BDNF in different biofluids in the blood (i.e., serum and plasma) with the intention of presenting a case for the most reliable and valid technique. Lastly, this review also explores potential moderators that can influence the measurement of BDNF and provides recommendations to standardize its quantification to reduce the inconsistencies across studies.
Methods
In this manuscript we examined the literature on BDNF, focusing on its role as a biomarker, its mechanism of action in NP, and critically analyzed its measurement in serum and plasma to identify factors that contribute to the discrepancy in results between plasma and serum BDNF values.
Results
A large heterogenous literature was reviewed that detailed BDNF's utility as a potential biomarker in healthy volunteers, patients with chronic pain, and patients with neuropsychiatric disorders but demonstrated inconsistent findings. The literature provides insight into the mechanism of action of BDNF at different levels of the central nervous system using animal studies. We identified multiple factors that influence the measurement of BDNF in serum and plasma and based on current evidence, we recommend assessing serum BDNF levels to quantify peripheral BDNF as they are more stable and sensitive to changes than plasma BDNF.
Conclusion
Although mechanistic studies clearly explain the role of BDNF, results from human studies are inconsistent. More studies are needed to evaluate the methodological challenges in using serum BDNF as a biomarker in NP.
Graphical
Preclinical studies support the role of BDNF as a biomarker in Neuropathic Pain. This study identified several methodological considerations that need to be accounted for when measuring BDNF peripherally. Additional longitudinal investigations are needed to develop standardized guidelines to measure serum BDNF and to clearly determine its role in the diagnosis and treatment of neuropathic pain.