| BackgroundIrritable bowel syndrome(IBS) is one of the most prevalent functional gastrointestinal disorders.The cardinal symptoms are abdominal pain accompanied with a change in bowel habit.However the pathogenesis of IBS is still incompletely known. Visceral hypersensitivity is considered to be an important pathophysiological mechanism in the development of pain or discomforte in IBS.Visceral hypersensitivity(low thresholds of visceral perception) contains both hyperalgesia and allodynia.Hyperalgesia refers to the enhanced response to a painful stimulus,and allodynia means a painful response to an innocuous stimulus.Currently, the descending modulation and accending arousal mechanisms are considered to be the causes or risk factors contributing to the visceral hypersensitivity in IBS.C-fos is an immediate-early gene.Its expression increased when neurons activated, which is considered to be a marker of neuronal activity.After somatic noxious stimulus, induction of c-fos protein mainly occurred in the nucleus of neurons involved in pain transduction pathway.Therefore,the c-fos encoded transcription factor is considered to be a marker of neuronal activity acossaited with visceral noxious stimulus.Serotonin(5-hydroxytryptamin,5-HT) is an important neurotransmitter,which plays a critical role in the signal transduction of nervous system.5%of 5-HT in the body locates in central nervous system(CNS).The dorsal raphe nucleus(DRN) contains most of the CNS 5-HT neurons.Its descending projections,via the nucleus raphe magnus or directly,modulate the spinal dorsal horn neurons,plays an important role on descending modulation of pain.So we assumed that the 5-HT of dorsal raphe nucleus might mediate the visceral hypersensitivity of IBS.AimsTo investigate the expression of 5-HT and c-fos of dorsal raphe nucleus in the model of visceral hypersensitivity,and discuss the role of 5-HT and c-fos expressed in dorsal raphe nucleus in the pathogenesis of IBS.Materials and methods(1) A total of 32 newborn Sprague-Dawley(SD) rats were randomized into two groups,16 rats for each:(A) Maternal separation group:Male neonatal SD rats were performed by a 3-h daily maternal separation on postnatal days 2-21;(B) Control group: no treatment on postnatal days 2-21.(2) On day 60,16 adult SD rats in group(A) were randomized into to two subgroups, subgroup(a) and subgroup(b),8 adult rates for each.As to group(B),16 adult SD rats were randomized into subgroup(c) and subgroup(d),8 adult rates for each.Colorectal distension(CRD) was performed to subgroup(b) and subgroup(d),subgroup(a) and subgroup(c) were left untreated.(3) And then the rats were fixed by perfusion of 40 g/L paraformaldehyde,brain tissue was obtained.(4) According to Paxinos atlas,we found the location of dorsal raphe nucleus,which was stained by immunohistochemistry assay and the expression of c-fos and 5-HT was observed.Results(1) Fo r maternal separation groups,the count of positive cells of c-fos in dorsal raphe nucleus(DRN) of brainstem with CRD was 114.00±9.82,significantly higher than that without CRD,80.88±11.27(#p＜0.001).(2) For control groups,the count of positive cells of c-fos in DRN of brainstem with and without CRD were 83.75±9.74 and 79.5±10.09 respectively(p＞0.05).(3) For maternal separation team,the count of positive cells of 5-HT in DRN of brainstem with and without CRD were 20.38±2.39 and 18.38±3.06 respectively (p＞0.05).(4) For control teams,the count of positive cells of 5-HT in DRN of brainstem with and without CRD were 17.75±4.46,and 18.75±2.49 respectively(p＞0.05).Conclusions(1) Dorsal raphe nucleus may be involved in perception of visceral nociceptive information and regulation of anomalies.(2) Early life stressful event,like neonatal maternal separation can lead to dysfunction of 5-HT system,in responsing to visceral stimuli.It may contribute to the understanding of the association of early life stressful event with visceral hyperalgesia. |
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