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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.
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1 Departamento de Biomedicina -Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal; Departamento de Urologia, Centro Hospitalar de São João, Porto, Portugal
2 Departamento de Biomedicina - Unidade de Farmacêutica e Terapêutica, Faculdade de Medicina da Universidade do Porto, Porto, Portugal; MedInUP – Center for Drug Discovery and Innovative Medicines, University Porto, Porto, Portugal
3 Departamento de Urologia, Centro Hospitalar de São João, Porto, Portugal; Serviço de Urologia Faculdade de Medicina da Universidade do Porto, Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal
4 Departamento de Biomedicina -Unidade de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, Porto, Portugal; i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal; IBMC – Instituto de Biologia Molecular e Celular, Universidade do Porto, Porto, Portugal