Partners in Crime: NGF and BDNF in Visceral Dysfunction

Abstract

: Neurotrophins (NTs), particularly Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF), have attracted increasing attention in the context of visceral function for some years. Here, we examined the current literature and presented a thorough review of the subject. : After initial studies linking of NGF to cystitis, it is now well-established that this neurotrophin (NT) is a key modulator of bladder pathologies, including Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC) and Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS. NGF is upregulated in bladder tissue and its blockade results in major improvements on urodynamic parameters and pain. Further studies expanded showed that NGF is also an intervenient in other visceral dysfunctions such as endometriosis and Irritable Bowel Syndrome (IBS). : More recently, BDNF was also shown to play an important role in the same visceral dysfunctions, suggesting that both NTs are determinant factors in visceral pathophysiological mechanisms. Manipulation of NGF and BDNF improves visceral function and reduce pain, suggesting that clinical modulation of these NTs may be important; however, much is still to be investigated before this step is taken. : Another active area of research is centered on urinary NGF and BDNF. Several studies show that both NTs can be found in the urine of patients with visceral dysfunction in much higher concentration than in healthy individuals, suggesting that they could be used as potential biomarkers. However, there are still technical difficulties to be overcome, including the lack of a large multicentre placebo-controlled studies to prove the relevance of urinary NTs as clinical biomarkers.

Blockade of BDNF signalling attenuates chronic visceral hypersensitivity in an IBS‐like rat model

“…Brain-derived neurotrophic factor (BDNF) and protein kinase Mζ (PKMζ), two of the molecules we examine in this study, critically contribute to LTP, memory and pain (Ji et al, 2003;Melemedjian et al, 2013;Price & Ghosh, 2013;Sacktor & Hell, 2017). Overexpression of BDNF has been linked to bladder inflammation, and the Val66Met mutation of BDNF can affect pain processing at the cortical level (Coelho, Oliveira, Antunes-Lopes, & Cruz, 2019). Recent studies have shown that BDNF contributes to visceral hypersensitivity in the colon (Fu et al, 2018;Zhang, Qin, Liu, Wang, & Yao, 2019).…”

Expression of BDNF and TrKB in Patients With Endometriosis and Their Correlation With Dysmenorrhea

“…A research found that there were no nerve cells in endometriotic lesions originally, but BDNF and NGF can promote the generation of nerve tissue in endometriotic lesions ( 28) and the expression level of BDNF and NGF is correlated with pain degree of endometriosis patients (29). However, another study showed that the expression level of BDNF and NGF was no signi cant correlation with the degree of pain (30). The manifestations of endometriosis pain in different types and locations are varying and the mechanisms are different between peritoneal endometriosis and deep in ltrating endometriosis (DIE), the former may be correlated with the stimulation of cytokines and growth factor generated by lesions, while the latter is correlated with stimulation of various factors, as well as the deep lesions as reported in previous study (31) (Fig.…”

BDNF and IL-8, But Not UCHL-1 and IL-11, Are Markers of Brain Injury in Children Caused by Mild Head Trauma

“…NGF binds to the tropomyosin receptor kinase A (TrkA) receptor, which activates ERK 1/2 and Akt pathways and stimulates the transcription of pro-survival genes and inhibits cell apoptosis. BDNF binds to the TrkB receptor [ 19 , 20 ]. Both NGF and BDNF bind to the non-specific neurotrophin (NT) receptor p75 [ 18 ].…”

“…A previous study presented that children with traumatic brain injury showed statistically higher BDNF than NGF levels, both in the cerebrospinal fluid and plasma [ 16 ]. BDNF plays a pivotal role in the survival of neurons, regulation of neurite outgrowth and maintenance of synaptic connectivity of the central nervous system [ 19 ]. Studies on animal models show that exogenous administration of neurotropic factors reduces or even prevents neurological deficits and cell death after brain injury [ 17 ].…”