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. METHODS: Thresholds to mechanical and thermal stimulation of the hind paw, visceromotor responses to colorectal distension and cystometrograms were performed in appropriate control and mice with experimentally-induced cystitis, inflammation of the hind or front paw, or injection of viral vectors encoding NGF or green fluorescent protein (GFP). RESULTS: 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. Hind paw inflammation and injection of the NGF-, but not the GFP-encoding viral vector or front paw inflammation, induced mechanical and thermal hyperalgesia in the affected hind paw and increased responses to colorectal distension without altering the micturition reflex. 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.