Spinal ERK activation contributes to the regulation of bladder function in spinal cord injured rats.
The extracellular signal-regulated kinase 1 and 2 (ERK) pathway, regulated by phosphorylation on specific amino acids, is emerging as an important signaling cascade in neurones, transducing sensory input into cellular responses. In the mammalian nervous system, the ERK pathway has been found to mediate plasticity events. Particularly, in the spinal cord, ERK play an important role in allodynia and hyperalgesia. Recently, it was demonstrated that ERK activation is upregulated in the spinal cord of rats with chronic bladder inflammation and contributes to bladder overactivity. Thus, in this study we sought to assess the involvement of ERK in micturition reflexes associated to spinal cord injury (SCI) in the rat. Bladder function in chronic SCI rats was altered compared to spinal intact rats. PhosphoERK levels were upregulated in the L6 spinal cord segment, particularly after saline infusion for 2 h. The increase in spinal ERK phosphorylation was specifically restricted to L6 spinal segment. No variation in the levels of total ERK protein was observed. Intrathecal administration of PD98059, a specific inhibitor of ERK phosphorylation, reduced the frequency and amplitude of bladder contractions in SCI animals but not in spinal intact ones. Overall, our results demonstrate increased activation of the ERK pathway in the spinal cord from SCI rats, restricted to spinal segments that receive sensory input arising from the bladder. Since the use of PD98059 reduced the frequency and amplitude of bladder contractions, ERK inhibitors may provide a new therapeutic approach to the treatment of bladder overactivity after spinal injuries.
Cruz
Célia D
CD
Institute of Histology and Embryology, Faculty of Medicine and IBMC, University of Porto, Portugal.
McMahon
Stephen B
SB
Cruz
Francisco
F
D000818:Animals; D004789:Enzyme Activation / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000201:enzymology*; D013119:Spinal Cord Injuries / Q000201:enzymology* / Q000503:physiopathology; D001743:Urinary Bladder / Q000201:enzymology / Q000502:physiology*; D001745:Urinary Bladder Diseases / Q000201:enzymology / Q000503:physiopathology
D048049:Extracellular Signal-Regulated MAP Kinases