The analgesic effect of refeeding on acute and chronic inflammatory pain.

Pain is susceptible to various cognitive factors. Suppression of pain by hunger is well known, but the effect of food intake after fasting (i.e. refeeding) on pain remains unknown. In the present study, we examined whether inflammatory pain behavior is affected by 24 h fasting and 2 h refeeding. In formalin-induced acute inflammatory pain model, fasting suppressed pain behavior only in the second phase and the analgesic effect was also observed after refeeding. Furthermore, in Complete Freund's adjuvant-induced chronic inflammatory pain model, both fasting and refeeding reduced spontaneous pain response. Refeeding with non-calorie agar produced an analgesic effect. Besides, intraperitoneal (i.p.) administration of glucose after fasting, which mimics calorie recovery following refeeding, induced analgesic effect. Administration of opioid receptor antagonist (naloxone, i.p.) and cannabinoid receptor antagonist (SR 141716, i.p.) reversed fasting-induced analgesia, but did not affect refeeding-induced analgesia in acute inflammatory pain model. Taken together, our results show that refeeding produce analgesia in inflammatory pain condition, which is associated with eating behavior and calorie recovery effect.

Uso da sacarose para o alívio da dor: repercussão na amamentação materna durante a internação do recém-nascido a termo / Use of sucrose for pain relief: consequences on breastfeeding of fullterm newborns during hospitalization

Durante o período de internação, o recém-nascido (RN) é submetido a uma série de procedimentos dolorosos ou não, que podem incidir sobre o seu comportamento e sobre a confiança da mãe para o cuidado e para a amamentação materna. Temos como questionamento, se sacarose 25% que é oferecida como medida de alivio da dor em RN a termo internado em alojamento conjunto interfere negativamente na amamentação materna exclusiva durante a internação. Objetivo: Verificar a associação entre uso da sacarose 25% que é oferecida como medida de alívio dor aguda em RN a termo, e a amamentação materna durante a internação em alojamento conjunto. Métodos: Trata-se de um estudo observacional, transversal, descritivo e analítico. A amostra foi constituída por 215 binômios cujo nascimento e internação ocorreram entre os meses de Junho a Setembro de 2017 em uma maternidade do interior paulista intitulada "Amiga da Criança". Os binômios foram incluídos no estudo somente após autorização da mãe, com assinatura de um termo de consentimento livre e esclarecido. Os dados foram coletados por meio do prontuário e planilhas especificas. Os RN foram divididos em dois grupos: RN expostos e não expostos ao uso da sacarose durante a internação. Como houve diferença estatística entre os grupos para o tempo de internação, para analisar a influência do uso da sacarose na amamentação durante toda internação, foi feita uma relativização das variáveis de aleitamento materno pelo total de dias de internação do RN. As associações foram verificadas pelo teste "U" de Mann-Whitney, com valor de p significativo para ? <= 0,05. Resultado: Dos 215 RN estudados durante toda internação, 111 (51,6%) RN foram expostos ao uso da sacarose. Foi utilizado sacarose para 188 (60,1%) dos procedimentos dolorosos, sendo que a mesma foi usada associada a outros métodos como o colo em 18 (5,7%) e sucção não nutritiva 64 (20,4%) dos procedimentos. Somando-se o uso isolado ou em associação a outras medidas, a sacarose foi utilizada 270 (86,2%) vezes sendo a medida mais aplicada na prática clínica da maternidade. No grupo que utilizou sacarose as médias de frequência de mamadas, uso de copo, translactação, tempo médio por mamada e amamentação assistida foram respectivamente: 7,9, 0,2, 0,5, 11,4 e 1,0 . No grupo que não utilizou a sacarose, respectivamente, as a médias das mesmas variáveis foram de 8,7, 0,03, 0,06, 18,6 e 0,8. Houve diferença estatisticamente significativa entre os grupos para as variáveis de alimentação: frequência de mamada (p=0,03), utilização de copo (p=0,01), realização de translactação (p=0,00), tempo médio por mamada (p=0,00) e amamentação assistida (p=0,02). Conclusão: As associações dos dados encontrados comprovaram a hipótese do presente estudo, ou seja o uso da sacarose a 25% para alívio da dor aguda influenciou negativamente na amamentação materna do RN durante a internação, pois, o grupo de RN que recebeu esta substância adocicada durante os procedimentos de punção arterial, venosa e capilar, apresentou menor frequência de mamada, menor tempo médio por mamada, maior uso de complemento lácteo, mais necessidade de translactação e necessitou de mais amamentação assistida por um profissional de enfermagem, quando comparado ao grupo de RN não expostos a ela. Faz-se necessária a inclusão de medidas não farmacológicas com a participação da mãe em substituição à sacarose, uma vez que tratou-se de pesquisa em uma Maternidade Amiga da Criança

Introduction: During the period of hospitalization, full-term newborns (NB) undergo a series of painful procedures, which may affect his behavior and the mother's confidence in both taking care of and breastfeeding the baby. We question whether 25% sucrose, which is offered as a measure of pain relief in hospitalized NB infants, negatively interferes with exclusive mother's breastfeeding during hospitalization in rooming-in care. Aim: Verify the association between the use of 25% sucrose offered as pain relief in full-term newborns and exclusive mother's breastfeeding during hospitalization in shared rooms. Methods: This is a study based on observation, and it is transversal, descriptive and analytical study. The sample consisted of 215 binomials whose birth and hospitalization occurred between June and September of 2017 in a maternity hospital in the countryside of São Paulo, in a Child-Friendly Maternity. The binomials were included in the study only after authorization obtained from the mother, with the signing of a free and previously informed consent form. The data were collected through medical records and specific worksheets. The NB were divided into two groups: NB exposed and not exposed to the use of sucrose during hospitalization, respectively. There was a statistical difference between the groups due to the hospitalization period; thus, to analyze the influence of sucrose use on breastfeeding during all hospitalization, a relative analysis of the variables of breastfeeding by the total number of days of hospitalization of the newborn was made. Associations were verified by the Mann-Whitney "U" test, with a significant p value for ? <= 0.05. Results: From 215 NBs studied during all hospitalization, 111 (51.6%) were exposed to the use of sucrose. Sucrose was applied for 188 (60.1%) of the painful procedures, and it was used in association with other methods such as lap in 18 (5.7%) and non-nutritive suction in 64 (20.4%) of the procedures. Added the isolate use or in association with other measures, sucrose was used 270 (86.2%) times, being the most applied measure in clinical practice of maternity. In the sucrose group, the average of frequency of feeding, cupping, translactation, average time per feeding and assisted breastfeeding were respectively: 7.9, 0.2, 0.5, 11.4 and 1.0. In the nonsucrose group, the average of the same variables were 8.7, 0.03, 0.06, 18.6 and 0.8, respectively. There was a statistically significant difference between the groups for feeding variables: feeding frequency (p = 0.03), cup use (p = 0.01), translactation (p = 0.00), average time per feed (p = 0.00) and assisted breastfeeding (p = 0.02). Conclusion: The associations of the data confirmed the hypothesis of the present study, that is, the use of sucrose at 25% for acute pain relief influenced negatively the maternal breastfeeding of newborns during hospitalization, since the group of newborns who received this sugary substance during the venous and capillary puncture procedures, presented lower breastfeeding frequency, lower average time for breastfeeding, greater use of milky complement, higher need for translactation and required more breastfeeding assisted by a nursing professional, when compared to the NB group who was not exposed to it. It is necessary to include non-pharmacological measures with the participation of the mother instead of sucrose, since it was a research in a Child-Friendly Maternity

The mitogen and stress-activated protein kinase 1 regulates the rapid epigenetic tagging of dorsal horn neurons and nocifensive behaviour.

Phosphorylation of histone H3 at serine 10 (p-H3S10) is a marker of active gene transcription. Using cognitive models of neural plasticity, p-H3S10 was shown to be downstream of extracellular signal-regulated kinase (ERK) signalling in the hippocampus. In this study, we show that nociceptive signalling after peripheral formalin injection increased p-H3S10 expression in the ipsilateral dorsal horn. This increase was maximal 30 minutes after formalin injection and occurred mainly within p-ERK-positive neurons. Spinal p-H3S10-enhanced expression was also observed in neurokinin 1 receptor (NK1R), c-Fos, and Zif268 positive neurons and was inhibited by ablation of serotonergic descending controls. The mitogen and stress-activated protein kinase 1 (MSK1) is downstream of ERK and can induce p-H3S10. We found that, after formalin injection, most phospho-MSK1 (p-MSK1)-positive cells (87% ± 3%) expressed p-ERK and the majority of p-H3S10-positive cells (85% ± 5%) expressed p-MSK1. Inhibition of ERK activity with the MEK inhibitor SL327 reduced formalin-induced p-ERK, p-MSK1, and p-H3S10, demonstrating that spinal p-MSK1 and p-H3S10 were at least partly downstream of ERK signalling. Crucially, pharmacological blockade of spinal MSK1 activity with the novel MSK1 inhibitor SB727651A inhibited formalin-induced spinal p-H3S10 and nocifensive behaviour. These findings are the first to establish the involvement of p-H3S10 and its main kinase, MSK1, in ERK regulation of nociception. Given the general importance of ERK signalling in pain processing, our results suggest that p-H3S10 could play a role in the response to injury.

Research design considerations for single-dose analgesic clinical trials in acute pain: IMMPACT recommendations.

This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.