Behavioral Pain Scores Research Articles

Suppressive Effect of Bortezomib on LPS-Induced Inflammatory Responses in Horses

Equine endotoxemia is a serious clinical problem with high mortality. Only a few treatments have been proved the therapeutic efficacy for equine endotoxemia. Excessive nuclear factor-kappa B (NF-κB) activation and production of proinflammatory cytokines, which were induced by reaction to lipopolysaccharide (LPS), would play a key role in the pathogenesis of endotoxemia. Bortezomib, a proteasome inhibitor, inhibits NF-κB signaling pathway through blocking proteasomal degradation of NF-κB inhibitor alpha. This study aimed to evaluate the effect of bortezomib on tumor necrosis factor-alpha (TNF-α) production by LPS-stimulated equine monocytes in vitro and on clinical and inflammatory parameters in an in vivo endotoxemia model. Bortezomib significantly inhibited LPS-induced TNF-α production through inhibition of NF-κB activity in vitro. In a cross over design, horses received pretreatment of either bortezomib (1.3 mg/m2) or vehicle (dimethyl sulfoxide) before the infusion of 30 ng/kg LPS. Clinical parameters including behavioral pain scores and hoof wall surface temperature (HWST) were measured over 7 hours. In an endotoxemia model, bortezomib had a tendency to improve painful reaction and reduction of HWST. Bortezomib would have a potential as a therapeutic agent for equine endotoxemia.

Abstract PR116

Background & Objectives: The ideal sedative agent should have both sedative and analgesic, minimal cardiovascular side effect, controllable respiratory side effect, rapid onset and offset of action, no accumulation in renal or hepatic dysfunction, has inactive metabolite and minimal interaction with other drugs. The aim of this study was to assess the efficacy between remifentanil and dexmedetomidine in term of haemodynamic, sedation and pain control during weaning in mechanically ventilated ICU patients. Materials & Methods: A prospective, randomized controlled trial was carried out in the SICU, after ethical approval. All patients were started on regular sedation with infusion midazolam and morphine until the decision for weaning was made by the specialist in-charge based on clinical assessment and investigations. During the weaning period, these drugs were discontinued and was replaced by either one of the study drugs. A total of 44 patients in the weaning process, were randomized equally into two groups for sedation in ICU for 6–72 hours. Patients in remifentanil group (R) received remifentanil with dosage range of 6-12microgram/kg/hour. Meanwhile, patient in dexmedetomidine group (D) received dexmedetomidine infusion with a range of 0.2–0.7 microgram/kg/hour. The patients were kept at Richmond Agitation Sedation Scale (RASS) of +1 to -1. Propofol (0.5–4.0 mg/kg/hour) was supplemented only in case of insufficient sedation at maximal remifentanil or dexmedetomidine dose. For remifentanil infusion, the infusion rate was titrated in stages to 0.1mcg/kg/min (6mcg/kg/hour) over a period of one hour prior to extubation. Patient’s haemodynamic RASS and Behavioral Pain Scale were documented. Patients will be excluded if they had not been extubated after 72 hours of starting the study drug infusion. Results: A total of 44 patients were enrolled in this study; 22 patients were given remifentanil infusion and another 22 patients were given dexmedetomidine infusion as sedation in ICU in the weaning process. There was no significant difference for SBP, MAP, HR, sedation score and behavioral pain score between (R) and (D) group during treatment period. However, there was a significant difference in DBP between (R) and (D) group with a mean (95% CI) of 67.29 (56.58, 112.64) and 84.61 (62.87,71.72) during the treatment period. There was a significant difference for sedation score when intragroup comparison for baseline and treatment period in remifentanil group (p =0.01). Similar result also was seen in the dexmedetomidine group, (p = 0.008). Conclusion: In conclusion, both remifentanil and dexmedetomidine regime can be used as sedation in patients with anticipated short-term duration of mechanical ventilation. Both regimes are equally well tolerated. Disclosure of Interest: None declared

Differential Effectiveness of Clinically-Relevant Analgesics in a Rat Model of Chemotherapy-Induced Mucositis.

Chemotherapy-induced intestinal mucositis is characterized by pain and a pro-inflammatory tissue response. Rat models are frequently used in mucositis disease investigations yet little is known about the presence of pain in these animals, the ability of analgesics to ameliorate the condition, or the effect that analgesic administration may have on study outcomes. This study investigated different classes of analgesics with the aim of determining their analgesic effects and impact on research outcomes of interest in a rat model of mucositis. Female DA rats were allocated to 8 groups to include saline and chemotherapy controls (n = 8). Analgesics included opioid derivatives (buprenorphine; 0.05mg/kg and tramadol 12.5mg/kg) and NSAID (carprofen; 15mg/kg) in combination with either saline or 5-Fluorouracil (5-FU; 150mg/kg). Research outcome measures included daily clinical parameters, pain score and gut histology. Myeloperoxidase assay was performed to determine gut inflammation. At the dosages employed, all agents had an analgesic effect based on behavioural pain scores. Jejunal myeloperoxidase activity was significantly reduced by buprenorphine and tramadol in comparison to 5-FU control animals (53%, p = 0.0004 and 58%, p = 0.0001). Carprofen had no ameliorating effect on myeloperoxidase levels. None of the agents reduced the histological damage caused by 5-FU administration although tramadol tended to increase villus length even when administered to healthy animals. These data provide evidence that carprofen offers potential as an analgesic in this animal model due to its pain-relieving efficacy and minimal effect on measured parameters. This study also supports further investigation into the mechanism and utility of opioid agents in the treatment of chemotherapy-induced mucositis.

Current Use of Pain Scores in Dutch Intensive Care Units: A Postal Survey in the Netherlands.

Pain is a common problem for critically ill patients treated in the intensive care unit (ICU) and can have serious consequences. For this reason, the appropriate recognition and treatment of pain is of extreme importance. However, pain assessment in critically ill patients can be challenging because these patients are often unable to self-report. To identify attitudes and practices regarding the assessment and management of pain in ICU patients unable to self-report, we surveyed all adult ICUs in the Netherlands. A multicenter, exploratory survey was sent by mail to all adult ICUs in the Netherlands. Eighty-four of 107 ICUs returned the questionnaire for a response rate of 79%. In patients able to self-report, 94% (n = 79; 95% confidence interval [CI], 86.7%-98%) of the ICUs used a standardized pain score. Visual Analog Scale and Numerical Rating Scale were used in 57% (n = 48; 99.3% CI, 41%-72%) and 48% (n = 40; 99.3% CI, 33%-64%), respectively. Nonteaching hospitals used pain assessment tools more often than teaching hospitals (P = 0.012). In patients not able to self-report, pain assessment tools were used in 19% (n = 16) of the ICUs. In the ICUs that used behaviorally based scoring systems, the Critical Care Pain Observation Tool and Behavioral Pain Scale (BPS) were used in 6% (n = 5; 99.5% CI, 1.1%-17%) and 5% (n = 4; 99.5% CI, 0.1%-15%), respectively. Among Dutch nurses, nursing opinion was considered the gold standard assessment in 36% (n = 30; 98.8% CI, 23%-50%) of the respondents, even when a patient was able to self-report and pain scales were used. In patients unable to self-report, nurses judged themselves to be more accurate than a behavioral pain assessment tool in 98% (n = 82; 98.8% CI, 89.7%-99.9%) of the patients. In the Netherlands, most ICUs used a standardized pain score in patients able to self-report. Nonteaching hospitals used pain assessment tools more often than teaching hospitals. In patients unable to self-report, pain is not routinely measured with a validated behavioral pain assessment tool. Almost all nurses in our survey felt that their assessment of patient pain was more accurate than behavioral pain assessment tools in patients unable to self-report. More research is needed to identify factors preventing more widespread acceptance of validated behavioral pain scores in patients unable to self-report.

Acupressure at BL60 and K3 Points Before Heel Lancing in Preterm Infants

Acupressure is an ancient Chinese healing art. In this pain-relieving method, the fingers are used to press key acupuncture points on the skin surface that stimulates the body׳s regulatory processes. The aim of this study was to investigate the effect of acupressure at Kun Lun (UB60) and Taixi (K3) points for pain management in preterm infants prior to heel lancing for blood collection. This was a prospective, randomized controlled study. The study setting was the neonatal intensive care unit at Baskent University Hospital in Turkey. A total of 32 preterm infants between 28 and 36 weeks׳ gestational age were randomly assigned to one of two groups: an acupressure group (n = 16) or a control group (n = 16). In the acupressure group, immediately before the heel prick, acupressure was applied for three minutes at UB60 and K3 points. A behavioral pain score was determined using the Premature Infant Pain Profile (PIPP) scale. There were no significant differences between the groups with respect to gestational age, birth weight, sex, mode of delivery, age at time of procedure, weight at time of procedure, or PIPP score. Mean duration of procedure and mean duration of crying were both shorter in the acupressure group (both P = .001). Applying acupressure at the BL60 and K3 points before heel lancing was associated with shorter procedural time and shorter duration of crying in preterm infants.

Cortical activity evoked by inoculation needle prick in infants up to one-year old.

Inoculation is one of the first and most common experiences of procedural pain in infancy. However, little is known about how needle puncture pain is processed by the central nervous system in children. In this study, we describe for the first time the event-related activity in the infant brain during routine inoculation using electroencephalography. Fifteen healthy term-born infants aged 1 to 2 months (n = 12) or 12 months (n = 5) were studied in an outpatient clinic. Pain behavior was scored using the Modified Behavioral Pain Scale. A distinct inoculation event-related vertex potential, consisting of 2 late negative-positive complexes, was observable in single trials after needle contact with the skin. The amplitude of both negative-positive components was significantly greater in the 12-month group. Both inoculation event-related potential amplitude and behavioral pain scores increased with age but the 2 measures were not correlated with each other. These components are the first recordings of brain activity in response to real-life needle pain in infants up to a year old. They provide new evidence of postnatal nociceptive processing and, combined with more traditional behavioral pain scores, offer a potentially more sensitive measure for testing the efficacy of analgesic protocols in this age group.

Ultrasound guided transversus abdominis plane block in pediatric patients undergoing laparoscopic surgery

ObjectiveTo assess safety and effectiveness of ultrasound-guided TAP block in children undergoing laparoscopic surgery for undescended testis.Subjects and methodsThis randomized controlled trial involved 108 children, 3–7 years old, randomly allocated into one of two equal groups; TAP Group and Control Group. All children received general anesthesia using propofol 1.5–2.5 mg/kg, atracurium 0.5 mg/kg and fentanyl 2 μg/kg. TAP Group received 0.5 ml/kg of ropivacaine 0.375% bilaterally under ultrasound guidance and control group received regular analgesics. Quality of analgesia was assessed using Children’s Hospital Eastern Ontario Pain Scale (CHEOPS) and Objective behavioral pain score (OPS). The primary outcome measures were hemodynamic parameters and degree of pain. Secondary outcome measures were intraoperative fentanyl requirement, postoperative rescue analgesia (time and dose), complications, hospital stay and degree of satisfaction of patients and their parents.ResultsTAP block group had significantly lower intraoperative fentanyl dose (p < 0.001), significantly longer time to first postoperative request of analgesic (p < 0.001), lower analgesic dose during the first postoperative 24 h (p < 0.001) and lower pain scores along the whole 24 postoperative hours. Mean arterial pressure and heart rate were within the clinically accepted range in the two groups. Parents’ satisfaction was significantly higher (p < 0.001) in the TAP block group.ConclusionTAP block under ultrasound guidance was easy, safe, reliable and effective analgesic in children undergoing laparoscopic surgery for undescended testis.

Analgesic effect of intra-articularly administered morphine, dexmedetomidine, or a morphine-dexmedetomidine combination immediately following stifle joint surgery in dogs.

To compare the analgesic effects of intra-articularly administered saline (0.9% NaCl) solution, morphine, dexmedetomidine, and a morphine-dexmedetomidine combination in dogs undergoing stifle joint surgery for cranial cruciate ligament rupture. Randomized, controlled, clinical trial. 44 dogs with cranial cruciate ligament rupture that underwent tibial tuberosity advancement (TTA) or tibial plateau leveling osteotomy (TPLO). Dogs received intra-articular injections of saline solution (0.2 mL/kg [0.09 mL/lb]), morphine (0.1 mg/kg [0.045 mg/lb]), dexmedetomidine (2.5 μg/kg [1.14 μg/lb]), or a combination of morphine (0.1 mg/kg) and dexmedetomidine (2.5 μg/kg). Intra-articular injections of the stifle joint were performed after completion of the corrective osteotomy procedure, just prior to skin closure. Signs of pain were assessed every 2 hours thereafter on the basis of mean behavioral and objective pain scores. Dogs with pain scores exceeding predetermined thresholds were given hydromorphone (0.05 mg/kg [0.023 mg/lb], SC) as rescue analgesia. Time to rescue analgesia did not significantly differ between dogs that underwent TTA versus TPLO. No significant difference in time to rescue analgesia was found among dogs receiving intra-articular injections of dexmedetomidine (median, 6 hours; range, 2 to 10 hours), morphine (median, 7 hours; range, 4 to 10 hours), or saline solution (median, 5 hours; range, 4 to 10 hours). However, time to rescue analgesia for dogs receiving intra-articular injection of the morphine-dexmedetomidine combination (median, 10 hours; range, 6 to 14 hours) was significantly longer than the time to rescue analgesia for other treatment groups. Intra-articular administration of the morphine-dexmedetomidine combination provided longer-lasting postoperative analgesia, compared with either morphine or dexmedetomidine alone, in dogs undergoing TTA or TPLO.

The Effect of Being in Mother’s Hug on Neonates’ Pain during Immunization

Abstract Background and aim: Pain is a complex phenomenon, which in the past were easily overlooked in infants. Pain relief is a basic need and rights of all human beings. The most obvious and most effective strategy for reducing neonatal pain and painful process of restricting the use of drugs and non-pharmacological methods of pain relief. The aim of this study was to examine the effect of being in mother’s hug on neonates’ pain during immunization Materials and methods: Mothers of 60 infants 2 to 4 months of your infant for vaccination were brought to health centers were invited to cooperate in the investigation. Samples were available. Infants were randomly divided into two groups of mothers and infants in arms control were. Data collection tools included a demographic questionnaire; Modified Behavioral Pain Scale. Data analysis using descriptive and inferential analyzes were conducted. Results: There were significant differences in Behavioral Pain Scores of two groups include: facial expression, cry, and movements (p<0.001). Conclusion: Findings regarding severity of pain in infants in the control group compared to the intervention group, Shows that Parents can be fed in order to reduce pain during painful procedures using safe and simple way to encourage. Key Words: Pain, Immunization, Neonate

CCL-1 in the spinal cord contributes to neuropathic pain induced by nerve injury

Cytokines such as interleukins are known to be involved in the development of neuropathic pain through activation of neuroglia. However, the role of chemokine (C-C motif) ligand 1 (CCL-1), a well-characterized chemokine secreted by activated T cells, in the nociceptive transmission remains unclear. We found that CCL-1 was upregulated in the spinal dorsal horn after partial sciatic nerve ligation. Therefore, we examined actions of recombinant CCL-1 on behavioural pain score, synaptic transmission, glial cell function and cytokine production in the spinal dorsal horn. Here we show that CCL-1 is one of the key mediators involved in the development of neuropathic pain. Expression of CCL-1 mRNA was mainly detected in the ipsilateral dorsal root ganglion, and the expression of specific CCL-1 receptor CCR-8 was upregulated in the superficial dorsal horn. Increased expression of CCR-8 was observed not only in neurons but also in microglia and astrocytes in the ipsilateral side. Recombinant CCL-1 injected intrathecally (i.t.) to naive mice induced allodynia, which was prevented by the supplemental addition of N-methyl-𝒟-aspartate (NMDA) receptor antagonist, MK-801. Patch-clamp recordings from spinal cord slices revealed that application of CCL-1 transiently enhanced excitatory synaptic transmission in the substantia gelatinosa (lamina II). In the long term, i.t. injection of CCL-1 induced phosphorylation of NMDA receptor subunit, NR1 and NR2B, in the spinal cord. Injection of CCL-1 also upregulated mRNA level of glial cell markers and proinflammatory cytokines (IL-1β, TNF-α and IL-6). The tactile allodynia induced by nerve ligation was attenuated by prophylactic and chronic administration of neutralizing antibody against CCL-1 and by knocking down of CCR-8. Our results indicate that CCL-1 is one of the key molecules in pathogenesis, and CCL-1/CCR-8 signaling system can be a potential target for drug development in the treatment for neuropathic pain.

2360 – Infants’ vaccination pain management and effect of breast feeding, sucking the pacifier and mother's hug: a randomized control trial

Infants’ vaccination pain management by using lowest side effect methods is very important. The aim of this study was to examine pain relieving effect of breast- feeding, sucking pacifier or being in mother's hug during DPT vaccination. This controlled trial study, was performed on 152) healthy2- 4 months term infants, whom was brought to the health centers of west of Tehran for DPT vaccination and their parents filled in informed consent. (Year 2008–2010) By randomized collection infants divided to three intervention group (Breast feeding, Sucking pacifier and being in mothers hug, and each group had intervention 2 minutes before, during, and 15 seconds after the injection) and control group, whom lied on the examining bed as routine of clinics (38 in each group). Objective changes in appearance of Neonates were assessed by Modified Behavioral Pain Scale (MBPS) during 5 second before immunization to 15 second after it. Descriptive and inferential statistics were used. All ethical points were considered and approved by Research ethics committee of TUMS and had registered in Iranian Registry of Clinical Trials (IRCT). Equality of age, gender and the time of feeding prior to vaccination were controlled. There were significant differences in Behavioral Pain Scores of four groups. (P < 0.0001) and routine group had highest pain score. Breast feeding is more analgesic than pacifier use with maternal holding. Maternal holding had less effect, but had more significant effect than routine. It is suggested to use these simple interventions during infant's vaccination.

The Use of the Faces, Legs, Activity, Cry and Consolability Scale to Assess Procedural Pain and Distress in Young Children

Young children frequently undergo diagnostic and therapeutic procedures in the emergency department (ED). Although developed and validated for postoperative pain, Face, Legs, Activity, Cry, Consolability (FLACC) behavioral pain scores have been recommended and used for the assessment of procedural pain as well. We set out to assess if FLACC scores can differentiate pain and distress and establish a hierarchy of FLACC scores experienced during common ED procedures. Prospective observational study at an urban tertiary children's hospital ED. We aimed to recruit 30 children each aged 6 to 42 months undergoing intravenous cannula (IV) insertion, nasogastric tube (NGT) insertion, metered dose inhaler (MDI) use and oxygen saturation (SpO(2)) measurement. Based on videotapes, 2 independent observers assessed pain and distress using FLACC scores during all procedural phases. A total of 125 patients were recruited and filmed for IV (33), NGT (30), MDI (34), and SpO2 (28). Median FLACC scores were as follows: NGT, 10 (interquartile range [IQR] 8.75-10); IV, 6.5 (IQR, 4.5-9.75); MDI, 6.5 (IQR, 0-9); and SpO(2), 0 (IQR, 0-0.5). The FLACC scores increased during each of the 3 phases, before the procedure, during restraint, and during the procedure. Procedural distress decreased with age except for NGT insertions, which remained very high irrespective of age. FLACC scores can be high during nonpainful procedures and the during restraint phase of painful procedures. This indicates that FLACC measures a composite of pain and distress in young children. This study identified substantial levels of pain and distress in young children by FLACC during commonly performed ED procedures, with nasogastric tube insertion having very high and intravenous cannulation/venepuncture and MDI having high FLACC scores.

Analysis of acute pain scores and skin conductance measurements in infants

BackgroundSkin conductance (SC) has been previously used to measure acute post-operative pain in adults and older children (>1year old).We have investigated the ability of SC to predict the severity of post-operative pain scores in the exclusively infant population. MethodsInfants (ages 6–12months) scheduled for elective surgery were recruited for the study. Data for behavioral pain scores and SC values — frequency of electrodermal responses per second (EDR/s), peak and basal levels, were recorded in the post-anesthesia care unit (PACU). Blood samples were collected for genomic studies, including single nucleotide polymorphisms (SNP) in morphine opioid receptor (MOR) A118G and the catechol-O-methyltransferase (COMT) G1947A genes. Results31 infants, mean age 8.9months (±1.9); mean weight 8.5kg (±1.1) were included in the final study analysis. With every 0.1 unit increase in peak values noted on SC, the odds of higher pain scores were found to be 5% greater (p=0.03). For predictability of moderate to severe pain, the area under the curve, sensitivity and specificity were 0.64, 90.9% and 51.4% respectively for peak values and 0.66, 54.5% and 79.4% respectively for EDR/s values. Genotyping performed in 16 out of 31 infants demonstrated that the carriers of MOR 118G allele had consistently higher basal SC values in the PACU. ConclusionPeak SC values may serve as indicators of unmitigated pain. Further studies are needed to fully investigate the effect of MOR A118G SNP on the post operative pain scores and SC values in the larger infant population in order to validate both the clinical significance of the skin conductance for routine pain assessment in infants and the observed genetic effect.

P-911 - Effect of breast feeding on infant's behavioral pain scale during DPT vaccination

Pain management is the challenging concepts in neonatal care. Since Neonates have higher pain sensitivity in comparison of childhood and adults, pain management has become crucial part of neonatal care and cure. To examine the pain relieving effect of breast feeding during DPT immunization injections in healthy neonates. 76 healthy 2– 4 months years old term infants, which had been brought to the health centers of Tehran University of Medical Sciences in West of Tehran for DPT vaccination by their mothers was involved in this randomized controlled trial study. (Their parents signed informed consent, Year 2008–2009) By randomized collection one group were breast-fed, 2 minutes before, during, and 15 seconds after the DPT immunization injection, and second group according to routine of clinic lied on the examining table during DPT Vaccination. Objective changes in appearance of Neonates were assessed by Modified Behavioral Pain Scale (MBPS) during 5 second before immunization till 15 second after it. The equality between two groups according to age, gender and the time of feeding prior to vaccination were checked, there weren’t correlation. There were significant differences in Behavioral Pain Scores of two groups in all parts include: facial expression (4 items), cry (5 items), and movements (6 items). (P < 0.0001) Regarding to significant difference in behavioral of Pain responds in two groups, it is suggested that, with simple and safe intervention of straight breast feeding, health care workers, and physicians reduce pain during immunization and muscular injections too.

1460 Pain Relief Effect of Mothers‚ Hug on Infants‚ Vaccination Pain in West of Tehran, 2009

Pain management of neonate is important.Aim: To Comprise pain relieving effect of mothers' hug with routine procedure of health centers during Infants' Vaccination.Material and Method: This controlled trial study, was performed on 76 healthy term infants with 2- 4 months years old, which was brought to the health centers of Iran University of Medical Sciences in west of Tehran by their parents and had DPT Vaccination. Volunteer parents filled in informed consent of research. By randomized collection 35 infants were given in their mothers' hug, during 2 minutes before vaccination till 15 seconds after it. Second group according to routine of clinics lied on the examining bed during Vaccination. Changes in appearance of Neonates were assessed by Modified Behavioral Pain Scale (MBPS) during 5 second before immunization till 15 second after it.Descriptive and inferential statistics were used. Median scores of 2 groups were compared with the Independent sample T test. Pre and post-scores of each group were compared with the Paired sample T test.Result: 15 second after vaccination average of pain was 8.36 in control group and 6.68 in experimental group. There were significant differences in Behavioral Pain Scores of two groups in all parts of tools. (P < 0.0001) There was no significant difference between the groups regarding gender.Conclusions: Regarding to significant difference in behavioral of pain responds in two groups, it is suggested that, with simple and safe intervention of hugging infants by their mothers reduce pain during vaccination and muscular injections too.

Oral sucrose as an analgesic drug for procedural pain in newborn infants: a randomised controlled trial

SummaryBackgroundMany infants admitted to hospital undergo repeated invasive procedures. Oral sucrose is frequently given to relieve procedural pain in neonates on the basis of its effect on behavioural and physiological pain scores. We assessed whether sucrose administration reduces pain-specific brain and spinal cord activity after an acute noxious procedure in newborn infants.MethodsIn this double-blind, randomised controlled trial, 59 newborn infants at University College Hospital (London, UK) were randomly assigned to receive 0·5 mL 24% sucrose solution or 0·5 mL sterile water 2 min before undergoing a clinically required heel lance. Randomisation was by a computer-generated randomisation code, and researchers, clinicians, participants, and parents were masked to the identity of the solutions. The primary outcome was pain-specific brain activity evoked by one time-locked heel lance, recorded with electroencephalography and identified by principal component analysis. Secondary measures were baseline behavioural and physiological measures, observational pain scores (PIPP), and spinal nociceptive reflex withdrawal activity. Data were analysed per protocol. This study is registered, number ISRCTN78390996.Findings29 infants were assigned to receive sucrose and 30 to sterilised water; 20 and 24 infants, respectively, were included in the analysis of the primary outcome measure. Nociceptive brain activity after the noxious heel lance did not differ significantly between infants who received sucrose and those who received sterile water (sucrose: mean 0·10, 95% CI 0·04–0·16; sterile water: mean 0·08, 0·04–0·12; p=0·46). No significant difference was recorded between the sucrose and sterile water groups in the magnitude or latency of the spinal nociceptive reflex withdrawal recorded from the biceps femoris of the stimulated leg. The PIPP score was significantly lower in infants given sucrose than in those given sterile water (mean 5·8, 95% CI 3·7–7·8 vs 8·5, 7·3–9·8; p=0·02) and significantly more infants had no change in facial expression after sucrose administration (seven of 20 [35%] vs none of 24; p<0·0001).InterpretationOur data suggest that oral sucrose does not significantly affect activity in neonatal brain or spinal cord nociceptive circuits, and therefore might not be an effective analgesic drug. The ability of sucrose to reduce clinical observational scores after noxious events in newborn infants should not be interpreted as pain relief.FundingMedical Research Council.

Effects of different time administration of parecoxib sodium on acute opioid tolerance after remifentanilbased anesthesia

Objective To investigate the effects of different time administration of parecoxib sodium on acute opioid tolerance after remifentanil-based anesthesia in patients.Methods Fifty-four ASA Ⅰ or Ⅱ patients aged 30-64 yr undergoing transabdominal cholecystectomy were randomly divided into 3 groups(n=18 each):group I received parecoxib 40 mg at 30 rain before anesthesia;group Ⅱ received parecoxib 40 mg at 30 min before termination of anesthesia;group C control.Anesthesia was induced and maintained with propefol and remifentanil administered via TCI.The target plasma concentration of propofol was set at 3μg/ml and that of remifentanil at 4 ng/ml.Tracheal intubation was facilitated with rocuronium 0.6 ms/ks.Muscle relaxation was maintained with intermittent iv boluses of vecuronium during operation.Pain was assessed using behavioral pain score(O=quiet and no pain,1=complaining,2=severe pain and/or agitation).When the pain score >0,the patients received iv injection of morphine and then PCIA with morphine(bolus dose 1 mg,lockout interval 5 min,no background infusion)30 min later.Morphine consumption and side effects were recorded within 30 min,and during 30 min-24 h and 24-48 h after operation.Results Compared with group C,the morphine consumption was significantly decreased during all the time periods within 48 h after operation in group I and during 30 rain-24 h and 24-48 h after operation in groupⅡ(P<0.05).The morphine cousumption was significantly higher within 30 min after operation in group Ⅱ than in group Ⅰ (P<0.05).No obvious side effects occurred in the 3 groups.Conclusion Parecoxib sodium 40 mg given before anesthesia can reduce acute opioid tolerance after remifentanil-based anesthesia in patients. Key words: Cyclooxygenuse inhibitors; Piperidines; Analgesics,opioid; Drug tolerance

Pre-natal stress amplifies the immediate behavioural responses to acute pain in piglets

Pre-natal stress (PNS) or undernutrition can have numerous effects on an individual's biology throughout their lifetime. Some of these effects may be adaptive by allowing individuals to tailor their phenotype to environmental conditions. Here we investigated, in the domestic pig Sus scrofa, whether one possible consequence of a predicted adverse environment could be altered pain perception. The behavioural response of piglets to the surgical amputation ('docking') of their tail or a sham procedure was measured for 1 min in piglets born to mothers who either experienced mid-gestation social stress or were left undisturbed throughout pregnancy. A behavioural pain score was found to predict the docked status of piglets with high discriminant accuracy. Piglets exposed to PNS had a significantly higher pain score than controls, and for each litter of tail-docked piglets, the average pain score was correlated with mid-gestation maternal cortisol levels. The data presented here provide evidence that the experience of stress in utero can result in a heightened acute response to injury in early life. Speculatively, this may represent an adaptive alteration occurring as a consequence of a pre-natal 'early warning' of environmental adversity.

Sucrose Decreases Infant Biobehavioral Pain Response to Immunizations: A Randomized Controlled Trial

To evaluate the effectiveness and age-related changes in analgesia of oral sucrose as a preprocedural intervention during routine immunizations in infants at 2 and 4 months of age. A double-blind, randomized, placebo-controlled clinical trial of 40 healthy term infants scheduled to receive routine immunizations from a pediatric ambulatory care clinic during May 2005 to July 2005. Infants received 24% oral sucrose solution or the control solution of sterile water 2 minutes before routine immunizations at both their 2- and 4-month, well-child visits. The University of Wisconsin Children's Hospital pain scale was used to measure serial acute behavioral pain responses at baseline, 2, and 5 minutes after administration of the solution. Repeated measures ANOVA was used to examine between-group differences and within-subject variability of the effects of treatment on overall behavioral pain scores. Infants receiving oral sucrose (n=20) showed a significant reduction in behavioral pain response 5 minutes after administration compared to those in the placebo group (n=20). At 2 minutes following solution administration, both sucrose and sterile water showed the highest mean pain score (4.54 and 4.39 respectively) indicating a severe amount of pain. At 5 minutes, the sucrose group returned to near normal at 0.27 while the placebo group remained at 3.02 indicating a percentage difference in mean pain scores relative to sterile water pain scores of 90.9. No statistically significant age-related change in behavioral pain response was noted between 2- and 4-month-old infants at 2 minutes and 5 minutes following treatment administration. Sucrose is an effective preprocedural intervention for decreasing behavioral pain response in infants after immunizations. Efforts to decrease the pain associated with immunizations can promote parental adherence to recommended immunizations schedules, prevent a resurgence of vaccine-preventable diseases and mitigate adverse neurologic outcomes in infants.

Regional brain activation in conscious, nonrestrained rats in response to noxious visceral stimulation

Preclinical drug development for visceral pain has largely relied on quantifying pseudoaffective responses to colorectal distension (CRD) in restrained rodents. However, the predictive value of changes in simple reflex responses in rodents for the complex human pain experience is not known. Male rats were implanted with venous cannulas and with telemetry transmitters for abdominal electromyographic (EMG) recordings. [ 14C]-iodoantipyrine was injected during noxious CRD (60 mmHg) in the awake, nonrestrained animal. Regional cerebral blood flow (rCBF)-related tissue radioactivity was quantified by autoradiography and analyzed in the three-dimensionally reconstructed brain by statistical parametric mapping. 60-mmHg CRD, compared with controls (0 mmHg) evoked significant increases in EMG activity (267 ± 24% vs. 103 ± 8%), as well as in behavioral pain score (77 ± 6% vs. 3 ± 3%). CRD elicited significant increases in rCBF as expected in sensory (insula, somatosensory cortex), and limbic and paralimbic regions (including anterior cingulate cortex and amygdala). Significant decreases in rCBF were seen in the thalamus, parabrachial nucleus, periaqueductal gray, hypothalamus and pons. Correlations of rCBF with EMG and with behavioral pain score were noted in the cingulate, insula, lateral amygdala, dorsal striatum, somatosensory and motor regions. Our findings support the validity of measurements of cerebral perfusion during CRD in the freely moving rat as a model of functional brain changes in human visceral pain. However, not all regions demonstrating significant group differences correlated with EMG or behavioral measures. This suggests that functional brain imaging captures more extensive responses of the central nervous system to noxious visceral distension than those identified by traditional measures.