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 not effective.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 in order to better understand the pathogenesis and investigate the effect of zeta inhibitory peptide(ZIP)as a therapy for chronic visceral pain.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.EMG responses to graded CRD pressure significantly increased in NMS rats compared to control rats(p < 0.05).p-PKMζ 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.Phosphorylated PKMζ may be involved in the spinal central sensitization of chronic visceral hypersensitivity in IBS,and administration of ZIP could be used as an effective treatment for chronic visceral pain with good outcomes in rat models.