Spinal NK1 receptor is upregulated after chronic bladder irritation.
It has been suggested that there is a significant upregulation of the NK1 receptor (NK1R) on neurons in the dorsal spinal cord after long-term somatic inflammation. This upregulation appears to play a significant role in central sensitization in chronic pain states. However, it is not clear whether such a change is also observed after chronic visceral (bladder) inflammation. Changes in NK1R immunoreactivity after chronic bladder irritation were investigated in order to evaluate the existence of hypersensitive states in the spinal cord after chronic bladder irritation. Experiments were performed on a total of 12 adult female Sprague-Dawley rats. In six animals, cyclophosphamide (CPA) was administered intraperitoneally for 2 weeks. Another six animals were given intraperitoneal saline injections and served as the control group. After these treatments, immunohistochemical staining for NK1Rs and substance P in rat lumbosacral spinal cord was performed. In CPA-treated animals, NK1R-positive areas and staining intensity within the dorsal spinal cord were significantly increased in the L5 to S2 spinal cord areas, especially in the L6 and S1 segments. In the L6 spinal segment, CPA-treatment enhanced NK1R immunostaining in the medial and the lateral dorsal horn, as well as in the lateral laminae including the sacral parasympathetic nucleus to a lesser extent. In CPA-treated animals, substance P staining intensity increased in the same regions in which NK1R immunoreactivity was increased. This finding probably implies the upregulation of spinal NK1R and the occurrence of central sensitization within the spinal cord after chronic visceral inflammation.
Ishigooka
Manabu
M
Department of Urology, Yamagata University School of Medicine, 2-2-2 Iida-Nishi, Yamagata 990-9585, Japan Neurourology Unit, Division of Urology, Colorado University Health Sciences Center, Denver, CO, USA.
Zermann
Dirk-Henrik
DH
Doggweiler
Ragi
R
Schmidt
Richard A
RA
Hashimoto
Tohru
T
Nakada
Teruhiro
T
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D003556:Cystitis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*; D001743:Urinary Bladder / Q000473:pathology
D018040:Receptors, Neurokinin-1