Abstract
Nerve growth factor (NGF) is thought to play a key role in chronic pain felt by bladder pain syndrome/interstitial cystitis (BPS/IC) patients by activating its high affinity receptor tropomyosin-related kinase subtype A (Trk A). Whether this pathway is also involved in the aggravation of pain sensation during stress events was here investigated. The levels of plasmatic NGF were increased in rats submitted to Water Avoidance Stress test (WAS), compared to controls. The administration of the alpha1A adrenoceptors blocker silodosin prevented the increase of plasmatic NGF. Urinary NGF levels were also moderately increased in animals submitted to WAS. WAS increased pain behaviour score, lowered abdominal mechanical pain threshold and increase voiding bladder reflex activity. These changes were prevented by the administration of TrkA antagonist GW441756. These findings prompt the use of plasmatic NGF as diagnosis tool for chronic visceral painful conditions and opens therapeutic opportunities for TrkA receptors antagonist/NGF sequestration.
Highlights
Nerve growth factor (NGF) is a master modulator of neural plasticity in particular of nociceptive peptidergic neurons, by recruiting, phosphorylating and activating the tropomyosin-related kinase subtype A (TrkA) receptor[1]
The administration of the apha1A antagonist silodosin during Water Avoidance Stress (WAS) induction prevented the increase in serum NGF levels (17.50 ± 0.53 pg/ml; ANOVA followed by Tukey’s multiple comparison test: p = 0.0001 compared to WAS and p = 1 compared with sham)
In animals stimulated by WAS test, serum NGF levels increased 114 times, by far exceeding the 3 times increment observed in the urine of the same animals
Summary
NGF is a master modulator of neural plasticity in particular of nociceptive peptidergic neurons, by recruiting, phosphorylating and activating the tropomyosin-related kinase subtype A (TrkA) receptor[1]. The high levels of NGF observed in BPS/IC patients have been attributed to the excess of synthesis and release of the neurotrophin from the bladder urothelium and detrusor smooth muscle cells[9,10]. BPS/IC patients report an increase in bladder pain intensity during stressful events[11] If such events cause an increase of NGF in the urine or in the serum, contributing to pain exacerbation, it is presently unknown. This information can be highly relevant in order to determine if patients under stressful conditions benefit from NGF sequestering strategy. We investigated the serum and urinary levels of NGF and the effect of the blockade of TrkA, the high affinity NGF receptor, in bladder pain and bladder function
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