title: Zeta Inhibitory Peptide as a Novel Therapy to Control Chronic Visceral Hypersensitivity in a Rat Model.
abstract: BACKGROUND
  The pathogenesis of multiple chronic visceral pain syndromes, such as irritable bowel syndrome (IBS), is not well known, and as a result current therapies are ineffective. The objective of this study was to investigate the effect of spinal protein kinase M zeta (PKMζ) on visceral pain sensitivity in rats with IBS to better understand the pathogenesis and investigate the effect of zeta inhibitory peptide (ZIP) as a therapy for chronic visceral pain.
  
  
  METHODS
  Visceral hypersensitivity rats were produced by neonatal maternal separation (NMS). Visceral pain sensitivity was assessed by electromyographic (EMG) responses of abdominal muscles to colorectal distention (CRD). Spinal PKMζ and phosphorylated PKMζ (p-PKMζ) were detected by western blot. Varying doses of ZIP were intrathecally administered to investigate the role of spinal PKMζ in chronic visceral hypersensitivity. The open field test was used to determine if ZIP therapy causes spontaneous motor activity side effects.
  
  
  RESULTS
  Graded CRD pressure significantly increased EMG responses in NMS rats compared to control rats (p < 0.05). p-PKMζ expression increased in the thoracolumbar and lumbosacral spinal cord in the IBS-like rats with notable concomitant chronic visceral pain compared to control rats (p < 0.05). EMG data revealed that intrathecal ZIP injection (1, 5, and 10 μg) dose-dependently attenuated visceral pain hypersensitivity in IBS-like rats.
  
  
  CONCLUSIONS
  Phosphorylated PKMζ may be involved in the spinal central sensitization of chronic visceral hypersensitivity in IBS, and administration of ZIP could effectively treat chronic visceral pain with good outcomes in rat models.
authors: Fujian Medical University, Basic Medical College, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province 350108, PR China.
authors: Ying
authors: Y
authors: Tang
authors: Fujian Medical University, Basic Medical College, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province 350108, PR China.
authors: Aiqin
authors: A
authors: Chen
authors: Fujian Medical University, Basic Medical College, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province 350108, PR China.
authors: Yu
authors: Y
authors: Chen
authors: Department of Pathology, Pingxiang People's Hospital, Pingxiang 337000, Jiangxi, PR China.
authors: Lixia
authors: L
authors: Guo
authors: Fujian Medical University, Basic Medical College, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province 350108, PR China.
authors: Hengfen
authors: H
authors: Dai
authors: Fujian Medical University, Basic Medical College, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province 350108, PR China.
authors: Yang
authors: Y
authors: Huang
authors: Fujian Medical University, Basic Medical College, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province 350108, PR China.
authors: Qianqian
authors: Q
authors: Chen
authors: Fujian Medical University, Basic Medical College, Laboratory of Pain Research, Key Laboratory of Brain Aging and Neurodegenerative Diseases, Neuroscience Research Center, Fuzhou City, Fujian Province 350108, PR China.
authors: Chun
authors: C
authors: Lin
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004576:Electromyography; D010455:Peptides / Q000627:therapeutic use*; D051381:Rats; D059265:Visceral Pain / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D010455:Peptides