title: Nerve growth factor mediates peripheral mechanical hypersensitivity that accompanies experimental cystitis in mice.
abstract: Increased sensitivity to somatic stimuli has been noted in the presence of visceral inflammation. Cystitis was induced by intraperitoneal injection of cyclophosphamide (CYP) in female mice. Sensitivity of hind paws to mechanical stimuli was determined prior to and 4, 9 and 24 h after CYP, and sensitivity of the tail to thermal stimuli was determined prior to, 4 and 24 h after CYP treatment. To investigate the role of nerve growth factor (NGF) in these processes, other groups of mice received NGF antiserum, normal serum, or K252a intravenously 30 min after CYP administration. CYP induced bladder inflammation that was not ablated by treatment with NGF antiserum or K252a. Sensitivity to mechanical stimuli was increased 4 and 9 h after CYP administration. This was reversed by NGF antiserum or K252a but not by normal serum. After 24 h, no differences were observed in withdrawal threshold among groups. None of the treatments had any effect on sensitivity to thermal stimuli. To further investigate the role of NGF in this process, NGF was instilled into the bladders of mice in the presence or absence of intravenous NGF antiserum. Four hours after intravesical instillation of NGF, the threshold of the hind paws to mechanical stimulation was significantly decreased, and this effect was reversed by prior treatment with NGF antiserum. This model of visceral pain causes increased sensitivity to peripheral application of mechanical stimuli. This effect is at least partially mediated by NGF, and the bladder may be the source of NGF in this process.
authors.affiliation: Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Dr., Madison, 53706, USA.
authors.forename: Simone Domit
authors.initials: SD
authors.lastname: Guerios
authors.forename: Zun-Yi
authors.initials: ZY
authors.lastname: Wang
authors.forename: Dale E
authors.initials: DE
authors.lastname: Bjorling
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D003556:Cystitis / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy* / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000627:therapeutic use*; D009929:Organ Size / Q000187:drug effects; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation / Q000009:adverse effects; D011930:Reaction Time / Q000187:drug effects; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000473:pathology
chemical_list: D003520:Cyclophosphamide; D020932:Nerve Growth Factor