How effective is tetracaine 4% gel, before a peripherally inserted central catheter, in reducing procedural pain in infants: a randomized double-blind placebo controlled trial [ISRCTN75884221]

BACKGROUND: Procedural pain relief is sub-optimal in infants, especially small and vulnerable ones. Tetracaine gel 4% (Ametop(®), Smith-Nephew) provides pain relief in children and larger infants, but its efficacy in smaller infants and for peripherally inserted central catheters (PICC) remains uncertain. The objective of this trial was to assess the safety and efficacy of tetracaine gel on the pain response of very low birth weight (VLBW) infants during insertion of a PICC. METHODS: Medically stable infants greater than or equal to 24 weeks gestation, requiring a non-urgent PICC, were included. Following randomization and double blinding, 1.1 g of tetracaine or placebo was applied to the skin for 30 minutes. The PICC was inserted according to a standard protocol. Pain was assessed using the Premature Infant Pain Profile (PIPP). A 3-point change in the pain score was considered clinically significant, leading to a sample size of 54 infants, with 90% statistical power. Local skin reactions and immediate adverse cardiorespiratory events were noted. The primary outcome, PIPP score at 1 minute, was analysed using an independent Student's t-test. RESULTS: Fifty-four infants were included, 27 +/- 2 weeks gestation, 916 +/- 292 grams and 6.5 +/- 3.2 days of age. Baseline characteristics were similar between groups. The mean PIPP score in the first minute was 10.88 in the treatment group as compared to 11.74 in the placebo group (difference 0.86, 95% CI -1.86, 3.58). Median duration of crying in non-intubated infants was 181 seconds in the tetracaine group compared to 68 seconds in the placebo group (difference -78, 95% CI -539, 117). Local skin erythema was observed transiently in 4 infants (3 in the treatment and 1 in the placebo group). No serious harms were observed. CONCLUSION: Tetracaine 4% when applied for 30 minutes was not beneficial in decreasing procedural pain associated with a PICC in very small infants

Genetic Evidence for Involvement of Neuronally Expressed S1P1 Receptor in Nociceptor Sensitization and Inflammatory Pain

Sphingosine-1-phosphate (S1P) is a key regulator of immune response. Immune cells, epithelia and blood cells generate high levels of S1P in inflamed tissue. However, it is not known if S1P acts on the endings of nociceptive neurons, thereby contributing to the generation of inflammatory pain. We found that the S1P1 receptor for S1P is expressed in subpopulations of sensory neurons including nociceptors. Both S1P and agonists at the S1P1 receptor induced hypersensitivity to noxious thermal stimulation in vitro and in vivo. S1P-induced hypersensitivity was strongly attenuated in mice lacking TRPV1 channels. S1P and inflammation-induced hypersensitivity was significantly reduced in mice with a conditional nociceptor-specific deletion of the S1P1 receptor. Our data show that neuronally expressed S1P1 receptors play a significant role in regulating nociceptor function and that S1P/S1P1 signaling may be a key player in the onset of thermal hypersensitivity and hyperalgesia associated with inflammation

A vibração torácica na fisioterapia respiratória de recém-nascidos causa dor? Does chest vibration during respiratory physiotherapy in neonates cause pain?

OBJETIVO: Avaliar a dor em recém-nascidos pré-termo (RNPT) submetidos à fisioterapia respiratória em Unidade de Terapia Intensiva Neonatal. MÉTODOS: Estudo transversal realizado com recém-nascidos prematuros, com indicação de fisioterapia respiratória, em respiração espontânea. Foi aplicada uma técnica de vibração torácica com a mão do terapeuta realizando pequenas oscilações sobre o tórax do paciente e feita a avaliação da frequência cardíaca (FC), frequência respiratória (FR), saturação de pulso de oxigênio (SpO2) e do Sistema de Codificação da Atividade Facial Neonatal (NFCS) para a avaliação da dor antes, durante, imediatamente após (pós-i) e 30 minutos após (pós-30) a vibração no tórax do paciente. Utilizou-se a análise de variância para medidas repetidas para comparação entre as fases, considerando-se significante p<0,05. RESULTADOS: Foram avaliados 13 RNPT, com média de idade gestacional 32,5±2,0 semanas e peso de nascimento 1830±442g. Não foi observada pontuação de dor durante toda a avaliação: pré: 0,5±1,7; durante: 1,5±1,4; pós-i: 1,0±1,3; pós-30: 0±0,3, porém houve diferença estatisticamente significativa entre a fase pós-i e pós-30 na escala NFCS (p<0,05). A FC variou de 120 a 150bpm, a SpO2 permaneceu acima de 95%, e a FR entre 40 e 62rpm, sem diferenças entre os períodos. CONCLUSÕES: Neste grupo de pacientes prematuros internados em UTI neonatal e submetidos à realização de fisioterapia respiratória pela técnica de vibração torácica, não foram observadas alterações fisiológicas e comportamentais de dor<br>OBJECTIVE: To observe pain score during chest physiotherapy (CP) in preterm newborns (PTNB) assisted in a Neonatal Intensive Care Unit. METHODS: A cross-sectional study was carried out with PTNB with spontaneous breathing that needed respiratory physiotherapy. A vibration technique was employed, with the hand of the therapist applying oscillations on the patients' thorax. The following variables were assessed: heart rate (HR), respiratory rate (RR) and oxygen saturation (O2Sat), as well as the Neonatal Facial Coding System (NFCS) to analyze pain before (pre), during, just after and 30 minutes after the thoracic vibration technique. Repeated measures analysis of variance was applied to analyze the protocol phases, being significant p<0.05. RESULTS: Thirteen PTNB were assessed. The mean gestational age was 32.5±2.0 weeks, and the birth weight was 1830±442g. No pain was observed during the evaluation: "pre": 0.5±1.7; "during": 1.5±1.4; "just after": 1.0±1.3; "30 min after": 0±0.3, but there was difference in the NFCS scores between the periods "just after" and "30 minutes after" (p<0.05). The HR varied between 120 and 150bpm, O2Sat levels remained over 95%, and RR oscillated from 40 to 62mpm, without differences between periods. CONCLUSIONS: Preterm patients spontaneously breathing and submitted to respiratory physiotherapy by thoracic vibration, no evidence of physiological or behavioral pain indicators were observe