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Presynaptic BDNF-TrkB signaling contributes to mechanical allodynia in a mouse model of chronic neuropathic pain

Year: 2025

Type: article

Abstract: In the spinal cord, brain-derived neurotrophic factor (BDNF) exerts its regulatory role on neuropathic pain through its receptor TrkB. This study constructed a conditional TrkB gene knockout mouse model, targeting all nociceptive neurons (SNS Cre ;TrkB fl/fl ) or all sensory neurons (Advillin Cre ;TrkB fl/fl ) in the dorsal root ganglia (DRG), to investigate the function of presynaptic BDNF-TrkB signaling in the dorsal horn and its impact on specific sensory modalities. In situ hybridization (ISH) was used to detect TrkB expression in nociceptive SNS tdTomato neurons, revealing that TrkB is expressed in both sensory neurons and nociceptors in the DRG. Triple immunofluorescence techniques were employed to detect the co-expression of neuron-specific markers NF200, CGRP, and IB4 with TrkB mRNA, and the co-expression ratios were analyzed. To assess motor function and aversive behavior, CatWalk (CW), home cage (HC), and wheel rotation (WR) tests were conducted; basic pain and touch sensitivity were evaluated using von Frey, cotton swabs, brush, pinprick, acetone, cold plate, Hargreaves, and hot plate tests, as well as tapping and hair clamp tests, with no effects observed on neurodevelopment, motor function, or aversive behavior. In addition, this study used the CCI model to conduct behavioral tests related to nerve injury in SNS Cre ;TrkB fl/fl and Advillin Cre ;TrkB fl/fl mice. After CCI surgery, both mouse strains exhibited severe dynamic and punctate mechanical allodynia deficits, while thermal and cold allodynia developed normally. Ultimately, by administering exogenous BDNF via intrathecal (IT) injection, mechanical allodynia deficits were observed in Advillin Cre ;TrkB fl/fl and SNS Cre ;TrkB fl/fl mice. The results confirmed that TrkB is expressed presynaptically and plays a role in the development of dynamic and punctate mechanical allodynia during BDNF-induced spinal plasticity responses, but has no effect on thermal or cold allodynia. In conjunction with previous studies, these findings suggest that BDNF may partially regulate presynaptic inhibition following nerve injury through TrkB. Fig. Abstract graphic of Presynaptic BDNF-TrkB signaling contributes to mechanical allodynia • TrkB is expressed in sensory neurons of the DRG and also in a small number of nociceptors. • The experiment successfully established SNS Cre ;TrkB fl/fl and Advillin Cre ;TrkB fl/fl mouse models, during the growth and development of these mice, the number and function of neurons remained intact, and there were no significant changes in motor ability and aversion response. • After CCI surgery, both SNS Cre ;TrkB fl/fl and Advillin Cre ;TrkB fl/fl mice showed defects in the formation and maintenance of punctate and dynamic mechanical allodynia, while no significant effects were observed in other sensory patterns such as thermal pain, etc. • In Both SNS Cre ;TrkB fl/fl and Advillin Cre ;TrkB fl/fl mice, IT injection of BDNF induced thermal pain sensitivity, but had no significant effect on mechanical pain hypersensitivity

Source: Brain Research Bulletin

DOI: 10.1016/j.brainresbull.2025.111625

Authors: Ting Ding, Lanying Zhang, Jingqing Xu, Maomao Liu, Yao Ou-Yang, Sheng Liu

Institutions: Zunyi Medical University, Heidelberg University

Language: English

Topic: Pain Mechanisms and Treatments

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,280