Convergence of sensory pathways in the development of somatic and visceral hypersensitivity

Abstract

Sensory neurons innervating different tissues converge onto second-order neurons in the spinal cord. We examined whether inflammation or transient overexpression of nerve growth factor (NGF) in one tissue triggers hypersensitivity in referral sites. Thresholds to mechanical and thermal stimulation of the hindpaw, visceromotor responses to colorectal distension, and cystometrograms were performed in appropriate controls and mice with experimentally induced cystitis, inflammation of the hindpaw or front paw, or injection of viral vectors encoding NGF or green fluorescent protein (GFP). Cystitis and NGF but not GFP overexpression in the bladder triggered bladder hyperactivity associated with mechanical and thermal hypersensitivity in cutaneous referral sites and enhanced responses to colorectal distension. Hindpaw inflammation and injection of the NGF- but not GFP-encoding viral vector or front paw inflammation induced mechanical and thermal hyperalgesia in the affected hindpaw and increased responses to colorectal distension without altering the micturition reflex. In conclusion, sensitization of sensory pathways by inflammation or NGF contributes to the development of hypersensitivity in neighboring organs and cutaneous referral sites and provides a potential mechanism underlying the coexistence of pain syndromes in patients with functional diseases.

Overexpression of NGF in mouse urothelium leads to neuronal hyperinnervation, pelvic sensitivity, and changes in urinary bladder function

“…Urinary bladder inflammation and hyperactivity induced by CYP (34) or intravesical turpentine (42), acrolein (35), or NGF (34) also triggers somatic hyperalgesia referred to the hindpaw, and this is attenuated by blockade of NGF by TrkAIgG (42) or immunoneutralization (35), or by blockade of Trk receptors using the nonselective tyrosine kinase inhibitor K252a (34,35). In one recent study (7), urinary bladder NGF overexpression led to enhanced responses to colorectal distension in addition to somatic mechanical and thermal hyperalgesia referred to the hindpaw, suggesting a role for NGF in the development of referred visceral and somatic hyperalgesia.…”

Urinary Bladder Function and Somatic Sensitivity in Vasoactive Intestinal Polypeptide (VIP)−/− Mice

“…Both neurotrophins (e.g., NGF) and cytokines/chemokines may contribute to urinary bladder hyperreflexia (Lamb et al, 2004;Vera and Meyer-Siegler, 2004;Hu et al, 2005;Yoshimura et al, 2006;Zvara and Vizzard, 2007) and increased somatic sensitivity (Abbadie, 2005;Bielefeldt et al, 2006;Guerios et al, 2006;Martinez and Melgar, 2008) in the presence of visceral inflammation. Current studies are determining if increased NGF expression drives cytokine/chemokine expression in the urinary bladder using an NGF-overexpressing mouse line under the control of the uroplakin II promoter.…”

Early assessment of patient satisfaction and health-related quality of life following robot-assisted radical prostatectomy

“…Convergence occurs through neurons at variable levels to innervate multiple pelvic organs and causes interactive cross-sensitization [14,15]. This phenomenon has been proposed to explain chronic pelvic pain disorders, and concurrent development of pelvic visceraviscero cross-talk irritation [15,16]. Thus, a comparison based on surgical technique based-comparison to assess pelvic visceral sensory convergence should be considered.…”