ABSTRACT
Objective To study the effects of painful procedures during neonatal period on rats' hippocampal gene expression in later life.Method A total of 28 newborn male rats were randomly assigned into two equal groups.From day1 (P1) to day7(P7) after birth,rats in the pain group received four times of needle acupuncture at the foot everyday,simulating the infants' experience in the NICU.Rats in control group were touched at the same side of the foot with a cotton swab.Transcriptome sequencing of the hippocampus of the two groups were examined on day 8 (P8) and day 21 (P21).The gene expression profiles were established and the differentially expressed genes were screened for functional analysis.Quantitative Real-time polymerase chain reaction (qRT-PCR) was used to confirm these differentially expressed genes (GABRB1,GRIN2A,IL1 RAPL1) related to pain-stimulated response or brain cognition,and one of the key genes was further verified using Western blotting.Result The sequencing results showed that there were only 6 differentially expressed genes in hippocampal tissues of rats on P8 in the two groups.Howerer,the number increased to 53 on P21 and 85.0％ of these genes were down-regulated (45/53).Gene Ontology (GO) function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the differentially expressed genes were mainly expressed on the cell membrane,voltage-gated ion channels,synapses,neurotransmitter receptors,immune responses,etc.The qRT-PCR and Western-blot results of key genes were consistent with the transcriptome sequencing.Conclusion Pain stimuli at an early stage after birth may trigger differentially expression of voltage-gated ion channel proteins,neurotransmitter receptors,and some key genes such as GABRB1 on hippocampal synaptic cell membranes in rats.These phenomenon may provide initial explanation for the molecular mechanism of early pain stimuli on neonatal brain development.
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Objective To explore the impact of early repetitive painful procedures on subsequent pain behaviors and physiological indicators in full-term infants.Methods Sixty-two full-term neonates were enrolled (male 36 cases,female 26 cases) from the medical center of neonatal care at Nanjing Children's Hospital Affiliated to Nanjing Medical University from March to May in 2009.The data of all painful procedures were performed on those neonates and their responses to them were collected by using digital video recording were collected.The Neonatal Facial Coding System C(NFCS) and Neonatal Infant Pain Scale(NIPS) were used prospectively to evaluate the pain response to painful procedures.Results The average experience of pain caused by operation on newborn at the hospital was 56.5 times (12-249 times),and the daily average was 5.9 times (4-26 times).After they were exposed to more than 10 repetitive pain procedures,the full-term neonates showed the declining pain response assessed by NFCS and NIPS during the subsequent painful procedures (NFCS:P10=0.012,P20=0.015,P30=0.041;NIPS:P10=0.006,P20=0.015,P30=0.049),and the temporarily enhanced pain response was observed in the preparation phase of the subsequent painful procedures (NFCS:P2＜0.001,P3＜0.001,P4=0.004,P5=0.009;NIPS:P2＜0.001,P3＜0.001,P4=0.045,P5 =0.031).Bnt there was no difference in preparation phase.There was no alternation in latency and crying time after repetitiing painful procedures,but the proportion of crying neonates in the preparation phase of the painful procedures was increased(P=0.032).Conclusions After exposed to repetitive pain,full-term neonates expressed hypoalgesia during subsequent painful procedures,but the temporary irritation was enhanced during the following phases exposed to stress.
ABSTRACT
Objective To evaluate the effects of repetitive noxious stimuli during the neonatal period on the pain sensitivity during adulthood in rats.Methods Twenty pathogen-free male neonatal SpragueDawley rats,weighing 6.2-6.8 g,were randomly divided into 2 groups (n=10 each) using a random number table:control group (group C) and repetitive noxious stimuli group (group RNS).In RNS group,neonatal rats sequentially received needle pricks into the dorsal surface of 4 paws at 6 h intervals with a 28 G needle per day during the first postnatal week.In group C,the animals received non-painful tactile stimuli with cotton tip rub.At the age of 10 weeks,complete Freund' s adjuvant was injected into the plantar surface of the right hind paw to induce inflammatory pain.Before injection,and at 24 h and 7 days after injection (T0-2),the mechanical and thermal thresholds were measured,and alcohol preference test was performed for assessment of the behavior at T2.Results The mechanical threshold of the right paws was significantly lower at T1.2 than that of the left paws in the two groups.Compared to group C,the mechanical threshold of the left and right paws at T0-2 and thermal threshold of the right paws at T1 were significantly decreased,and alcohol intake was increased in group RNS.Conclusion Repetitive noxious stimuli during the neonatal period can lead to increase in the pain sensitivity during adulthood in rats.