Acute Visceral Pain in Rats: Vagal Nerve Block Compared to Bupivacaine Administered Intramuscularly.

BACKGROUND: Visceral and parietal peritoneum layers have different sensory innervations. Most visceral peritoneum sensory information is conveyed via the vagus nerve to the nucleus of the solitary tract (NTS). We already showed in animal models that intramuscular (i.m.) injection of local anesthetics decreases acute somatic and visceral pain and general inflammation induced by aseptic peritonitis. The goal of the study was to compare the effects of parietal block, i.m. bupivacaine, and vagotomy on spinal cord and NTS stimulation induced by a chemical peritonitis. METHODS: We induced peritonitis in rats using carrageenan and measured cellular activation in spinal cord and NTS under the following conditions, that is, a parietal nerve block with bupivacaine, a chemical right vagotomy, and i.m. microspheres loaded with bupivacaine. Proto-oncogene c-Fos (c-Fos), cluster of differentiation protein 11b (CD11b), and tumor necrosis factor alpha (TNF-α) expression in cord and NTS were studied. RESULTS: c-Fos activation in the cord was inhibited by nerve block 2 hours after peritoneal insult. Vagotomy and i.m. bupivacaine similarly inhibited c-Fos activation in NTS. Forty-eight hours after peritoneal insult, the number of cells expressing CD11b significantly increased in the cord (P = .010). The median difference in the effect of peritonitis compared to control was 30 cells (CI95, 13.5-55). TNF-α colocalized with CD11b. Vagotomy inhibited this microglial activation in the NTS, but not in the cord. This activation was inhibited by i.m. bupivacaine both in cord and in NTS. The median difference in the effect of i.m. bupivacaine added to peritonitis was 29 cells (80% increase) in the cord and 18 cells (75% increase) in the NTS. Our study underlines the role of the vagus nerve in the transmission of an acute visceral pain message and confirmed that systemic bupivacaine prevents noxious stimuli by inhibiting c-Fos and microglia activation. CONCLUSIONS: In rats receiving intraperitoneal carrageenan, i.m. bupivacaine similarly inhibited c-Fos and microglial activation both in cord and in the NTS. Vagal block inhibited activation only in the NTS. Our study underlines the role of the vagus nerve in the transmission of an acute visceral pain message and confirmed that systemic bupivacaine prevents noxious stimuli. This emphasizes the effects of systemic local anesthetics on inflammation and visceral pain.

The Application of Fascia Iliaca Compartment Block for Acute Pain Control of Hip Fracture and Surgery.

PURPOSE OF REVIEW: Over 300,000 patients are hospitalized annually following hip fractures in the USA. Many patients experienced inadequate analgesia. We will review the perioperative effects of the fascia iliaca compartment block (FICB) in hip fracture patients. RECENT FINDINGS: FICB by injecting local anesthetics beneath the fascia iliaca results in significant pain relief in hip fractures. Neuropathies and vascular injuries are almost unlikely. Single-shot FICB is faster to place, yet providing about 8 h of analgesia when bupivacaine is used. Continuous FICB provides prolonged titratable analgesia, improved patient satisfaction, and leads to faster hospital discharge. FICB reduces opioid consumption, decreases morbidity and mortality, reduces hospital stay, reduces delirium, and improves satisfaction. FICB should form part of a multimodal analgesic regime, in the context of a multidisciplinary approach to the management of hip fracture patients. More clinical investigations are needed to validate the long-term outcome benefits of FICB in hip fracture patients.

Risk Factors Associated With Transition From Acute to Chronic Low Back Pain in US Patients Seeking Primary Care.

Importance: Acute low back pain (LBP) is highly prevalent, with a presumed favorable prognosis; however, once chronic, LBP becomes a disabling and expensive condition. Acute to chronic LBP transition rates vary widely owing to absence of standardized operational definitions, and it is unknown whether a standardized prognostic tool (ie, Subgroups for Targeted Treatment Back tool [SBT]) can estimate this transition or whether early non-guideline concordant treatment is associated with the transition to chronic LBP. Objective: To assess the associations between the transition from acute to chronic LBP with SBT risk strata; demographic, clinical, and practice characteristics; and guideline nonconcordant processes of care. Design, Setting, and Participants: This inception cohort study was conducted alongside a multisite, pragmatic cluster randomized trial. Adult patients with acute LBP stratified by SBT risk were enrolled in 77 primary care practices in 4 regions across the United States between May 2016 and June 2018 and followed up for 6 months, with final follow-up completed by March 2019. Data analysis was conducted from January to March 2020. Exposures: SBT risk strata and early LBP guideline nonconcordant processes of care (eg, receipt of opioids, imaging, and subspecialty referral). Main Outcomes and Measures: Transition from acute to chronic LBP at 6 months using the National Institutes of Health Task Force on Research Standards consensus definition of chronic LBP. Patient demographic characteristics, clinical factors, and LBP process of care were obtained via electronic medical records. Results: Overall, 5233 patients with acute LBP (3029 [58%] women; 4353 [83%] White individuals; mean [SD] age 50.6 [16.9] years; 1788 [34%] low risk; 2152 [41%] medium risk; and 1293 [25%] high risk) were included. Overall transition rate to chronic LBP at six months was 32% (1666 patients). In a multivariable model, SBT risk stratum was positively associated with transition to chronic LBP (eg, high-risk vs low-risk groups: adjusted odds ratio [aOR], 2.45; 95% CI, 2.00-2.98; P < .001). Patient and clinical characteristics associated with transition to chronic LBP included obesity (aOR, 1.52; 95% CI, 1.28-1.80; P < .001); smoking (aOR, 1.56; 95% CI, 1.29-1.89; P < .001); severe and very severe baseline disability (aOR, 1.82; 95% CI, 1.48-2.24; P < .001 and aOR, 2.08; 95% CI, 1.60-2.68; P < .001, respectively) and diagnosed depression/anxiety (aOR, 1.66; 95% CI, 1.28-2.15; P < .001). After controlling for all other variables, patients exposed to 1, 2, or 3 nonconcordant processes of care within the first 21 days were 1.39 (95% CI, 1.21-2.32), 1.88 (95% CI, 1.53-2.32), and 2.16 (95% CI, 1.10-4.25) times more likely to develop chronic LBP compared with those with no exposure (P < .001). Conclusions and Relevance: In this cohort study, the transition rate to chronic LBP was substantial and increased correspondingly with SBT stratum and early exposure to guideline nonconcordant care.

Preoperative Chronic and Acute Pain Affects Postoperative Cognitive Function Mediated by Neurotransmitters.

The effective prevention of postoperative cognitive dysfunction (POCD) needs to be explored, and the effect of preoperative pain on POCD remains unclear. We established a chronic pain model induced by chronic constriction injury (CCI) and models of acute pain and anxiety without pain in mice that were subsequently subjected to partial hepatectomy surgery. Morris water maze (MWM) tests were performed to evaluate the learning and memory abilities of the mice. ELISA was used to measure IL-1ß, IL-6, and TNF-α in serum, and HPLC-MS was used to detect neurotransmitters in the prefrontal cortices and hippocampi of the mice. The results indicated that chronic pain induced by CCI might have significantly impaired the learning and memory abilities of mice, while acute pain and anxiety without pain only affected the memory abilities of mice. Perioperative acute pain increased the level of IL-1ß in serum, and CCI might have increased the level of IL-6. CCI and acute pain increased dopamine (DA) levels in the cortex, similar to anxiety. Like anxiety, CCI increased 5-hydroxytryptamine (5-HT) levels in the prefrontal cortex and hippocampus. Acute pain led to a decrease in the acetylcholine (ACH) level in the hippocampus. Our results suggest that acute pain and CCI-induced chronic pain might aggravate postoperative cognitive dysfunction via neurotransmitters and by changing the levels of inflammatory factors such as IL-1ß and IL-6.

Severity of intervertebral disc herniation regulates cytokine and chemokine levels in patients with chronic radicular back pain.

OBJECTIVE: The contributions of intervertebral disc disease and subject-specific covariates to systemic inflammation in low back pain are unknown. We examined the effects of symptomatic disc herniation (DH) and MRI herniation severity on serum cytokine levels in clinical subjects. DESIGN: Cytokine levels from lumbar DH subjects (N = 78) were compared to control subjects (N = 57) accounting for effects of DH, age, body mass index (BMI) and gender. Effect of DH severity on cytokine levels was analyzed on subsets of subjects with acute or chronic pain. Serum cytokines were also analyzed in a subset of patients between pre- and 3 months post-surgery. RESULTS: Cytokine levels were elevated in the serum of patients with symptomatic DH, and the covariates age, BMI and gender significantly contributed to levels of some cytokines. Severity of herniation was a significant contributor to pain intensity (VAS), serum levels of HMGB1, PDGFbb, and IL-9. The relationship between DH severity and cytokine levels was confirmed in subjects with chronic, but not acute symptoms. Serum levels of macrophage migration inhibitory factor (MIF) decreased, whereas levels of CCL3, CCL11, CXCL1, and CXCL10 were significantly elevated post surgery. CONCLUSIONS: This study is the first to show that DH severity is coordinately associated with changes in serum levels of inflammatory cytokines in chronic pain subjects. HMGB1, PDGFbb and IL-9 are novel mediators of increasing DH severity, indicative of cellular damage, neuro-inflammation and angiogenesis. Resolution of inflammation was observed with decrease in MIF post surgery. However, elevated chemokine levels indicate ongoing remodeling and wound healing at 3-month time point.

Preemptive and Preventive Pain Psychoeducation and Its Potential Application as a Multimodal Perioperative Pain Control Option: A Systematic Review.

The common treatment for postoperative pain is prescription opioids. Yet, these drugs have limited effect in preventing chronic pain from surgical intervention and have in part contributed to the opioid epidemic. Recently, preemptive analgesia and multimodal analgesia have been proposed with widely gained acceptance in addressing the pain issues. However, both analgesic approaches have been focused on pharmacological means while completely neglecting the psychological aspect. To address this epidemic, we have conducted a systematic review of preoperative educational methods to explore its application as both a preemptive and a preventive psychological approach to decrease postsurgical pain and improve outcome. Preemptive psychoeducation occurs before surgery and would include information about regional or neuraxial analgesia, while preventive psychoeducation occurs throughout the perioperative period. The content and presentation of preemptive psychoeducation can help patients form accurate expectations and address their concerns of surgical outcome, leading to a significant decrease in patients' anxiety levels. By addressing the psychological needs of patients through preoperative education, one can decrease postoperative recovery time and postsurgical acute pain. Reduced postsurgical acute pain results in fewer opioid prescriptions, which theoretically lowers the patient's risk of developing chronic postsurgical pain (CPSP), and potentially offers a novel concept using preemptive pain psychoeducation as a part of multimodal pain management solution to the opioid epidemic.

Proliferator-Activated Receptor-Gamma Coactivator-1α Haploinsufficiency Promotes Pain Chronification After Burn Injury.

BACKGROUND: Tissue injuries such as surgery and trauma are usually accompanied by simultaneous development of acute pain, which typically resolves along with tissue healing. However, in many cases, acute pain does not resolve despite proper tissue repair; rather, it transitions to chronic pain. In this study, we examined whether proliferator-activated receptor-gamma coactivator-1α (PGC-1α), a master regulator of mitochondria biogenesis, is implicated in pain chronification after burn injury in mice. METHODS: We used PGC-1α and littermates PGC-1α mice of both sex. Burn injury was induced on these mice. Hindpaw mechanical withdrawal thresholds and thermal withdrawal latency were examined. RESULTS: Hindpaw mechanical withdrawal thresholds and thermal withdrawal latencies were comparable at baseline between PGC-1α and PGC-1α mice. After burn injury, both PGC-1α and PGC-1α mice exhibited an initial dramatic decrease of withdrawal parameters at days 3 and 5 after injury. While PGC-1α mice fully recovered their withdrawal parameters to preinjury levels by days 11-14, PGC-1α mice failed to recover those parameters during the same time frame, regardless of sex. Moreover, we found that PGC-1α mice resolved tissue inflammation in a similar fashion to PGC-1α mice using a chemiluminescence-based reactive oxygen species imaging technique. CONCLUSIONS: Taken together, our data suggest that PGC-1α haploinsufficiency promotes pain chronification after burn injury.

Nonopioid Modalities for Acute Postoperative Pain in Abdominal Transplant Recipients.

The field of abdominal organ transplantation is multifaceted, with the clinician balancing recipient comorbidities, risks of the surgical procedure, and the pathophysiology of immunosuppression to ensure optimal outcomes. An underappreciated element throughout this process is acute pain management related to the surgical procedure. As the opioid epidemic continues to grow with increasing numbers of transplant candidates on opioids as well the increase in the development of enhanced recovery after surgery protocols, there is a need for greater focus on optimal postoperative pain control to minimize opioid use and improve outcomes. This review will summarize the physiology of acute pain in transplant recipients, assess the impact of opioid use on post-transplant outcomes, present evidence supporting nonopioid analgesia in transplant surgery, and briefly address the perioperative approach to the pretransplant recipient on opioids.

Short-Term Recovery Trajectories of Acute Flares in Knee Pain: A UK-Netherlands Multicenter Prospective Cohort Analysis.

OBJECTIVE: To identify distinct recovery trajectories of acute flares of knee pain and associated participant characteristics. METHODS: Data were from the FLARE randomized controlled trial, a multicenter trial in 27 primary care centers in the UK and Netherlands of 3 regimes of oral nonsteroidal antiinflammatory therapy for acute flares of knee pain. Individuals with a history of inflammatory/crystal arthritis, fibromyalgia, and chronic pain syndrome were excluded. Latent class growth analysis was applied to measures of pain intensity repeated over 5 days to identify distinct recovery trajectories. The concurrent courses of interference with activity, stiffness, and swelling for each trajectory group were modelled using generalized estimating equations. Participant age, sex, obesity, and osteoarthritis diagnosis were described for each trajectory group. RESULTS: A total of 449 participants were included (median age 55 years, 41% female, 35% obese, and 42% diagnosed with osteoarthritis). A 6-group cubic model was deemed optimal, with trajectories distinguished by rate of pain reduction and absolute level at final measurement. At the extremes were rapid and near-complete resolution (n = 41, 9%) and persistent, high pain (n = 25, 6%), but most participants showed a reduction and plateau in pain severity within 3-5 days. Within each pain trajectory group, interference with activity, stiffness, and swelling followed the same course as pain. Baseline characteristics did not differ substantially between trajectory groups. CONCLUSION: Even under a well-adhered to regime of oral nonsteroidal antiinflammatory medication, recovery following acute flares of knee pain is heterogeneous. Our observations that favorable trajectories are apparent within 3-5 days can help to inform treatment decision-making in the patient-health care professional consultation.

[Calcitonin as an analgesic agent: review of mechanisms of action and clinical applications]. / Calcitonina como agente analgésico: revisão dos mecanismos de ação e das aplicações clínicas.

BACKGROUND AND OBJECTIVES: Calcitonin is a polypeptide hormone regulating the metabolism calcium in the body. For many years calcitonin has been used to maintain and improve bone mineral density and to reduce the fracture rate. Many studies showed that calcitonin had analgesic role in several painful circumstances. This pain-ameliorating effect is irrelevant to its osteoclastic inhibitory effect and mechanisms like altering Na+ channel and serotonin receptor expression or hypothesis including the endorphin-mediated mechanism were used to explain this effect. In this study we performed a thorough review on the role of calcitonin as an analgesic agent in different scenarios and investigated the fact that calcitonin can be a feasible medication to relieve pain. METHOD: Many studies focused on the analgesic effect of calcitonin in several painful circumstances, including acute pains related to vertebral fractures, metastasis, migraine and reflex sympathetic dystrophy as well as neuropathic pains related to spinal injuries or diabetes, and phantom pain. Also, calcitonin was showed to be a useful additive to local anesthesia in the case of controlling postoperative pain or trigeminal neuralgia more effectively. However we faced some contradictory data for conditions like lumbar canal stenosis, complex regional pain syndrome, phantom pain and malignancies. CONCLUSION: This study showed that calcitonin could be helpful analgesic agent in different painful situations. Calcitonin can be considered an eligible treatment for acute pains related to vertebral fractures and a feasible alternative for the treatment of the acute and chronic neuropathic pains where other medications might fail.

Calcitonin as an analgesic agent: review of mechanisms of action and clinical applications / Calcitonina como agente analgésico: revisão dos mecanismos de ação e das aplicações clínicas

Abstract Background and objectives: Calcitonin is a polypeptide hormone regulating the metabolism of calcium in the body. For many years calcitonin has been used to maintain and improve bone mineral density and to reduce the fracture rate. Many studies showed that calcitonin had analgesic role in several painful circumstances. This pain-ameliorating effect is irrelevant to its osteoclastic inhibitory effect and mechanisms like altering Na+ channel and serotonin receptor expression or hypothesis including the endorphin-mediated mechanism were used to explain this effect. In this study we performed a thorough review on the role of calcitonin as an analgesic agent in different scenarios and investigated the fact that calcitonin can be a feasible medication to relieve pain. Method: Many studies focused on the analgesic effect of calcitonin in several painful circumstances, including acute pains related to vertebral fractures, metastasis, migraine and reflex sympathetic dystrophy as well as neuropathic pains related to spinal injuries or diabetes, and phantom pain. Also, calcitonin was showed to be a useful additive to local anesthesia in the case of controlling postoperative pain or trigeminal neuralgia more effectively. However we faced some contradictory data for conditions like lumbar canal stenosis, complex regional pain syndrome, phantom pain and malignancies. Conclusion: This study showed that calcitonin could be helpful analgesic agent in different painful situations. Calcitonin can be considered an eligible treatment for acute pains related to vertebral fractures and a feasible alternative for the treatment of the acute and chronic neuropathic pains where other medications might fail.

Resumo Justificativa e objetivos: A calcitonina é um hormônio polipeptídico que regula o metabolismo do cálcio no organismo. Por muitos anos a calcitonina tem sido usada para manter e melhorar a densidade mineral óssea e reduzir a incidência de fraturas. Muitos estudos mostraram que a calcitonina teve efeito analgésico em várias condições físicas de dor. Esse efeito de melhoria da dor é irrelevante diante de seu efeito inibidor osteoclástico e de mecanismos, tais como a alteração do canal de Na+ e da expressão do receptor de serotonina, inclusive a hipótese do mecanismo mediado pela endorfina, que foram usados para explicar esse efeito. Neste estudo, fizemos uma revisão completa sobre o papel da calcitonina como agente analgésico em diferentes cenários e investigamos o fato de que a calcitonina pode ser uma medicação viável para aliviar a dor. Método: Muitos estudos centraram no efeito analgésico da calcitonina em várias condições de dor, inclusive dores agudas relacionadas a fraturas vertebrais, metástases, enxaqueca e distrofia simpática reflexa, bem como dores neuropáticas relacionadas a lesões medulares ou ao diabetes e dor fantasma. Além disso, a calcitonina mostrou ser um aditivo útil à anestesia local para o controle mais efecaz da dor pós-operatória ou neuralgia do trigêmeo. Porém, nos deparamos com alguns dados contraditórios em condições como estenose do canal lombar, síndrome complexa da dor regional, dor fantasma e malignidades. Conclusão: Este estudo mostrou que a calcitonina pode ser um analgésico útil em diferentes condições de dor. A calcitonina pode ser considerada um tratamento elegível para as dores agudas relacionadas a fraturas vertebrais e uma opção viável para o tratamento das dores neuropáticas agudas e crônicas em que outros medicamentos podem falhar.

New and emerging treatments for vaso-occlusive pain in sickle cell disease.

Introduction: Acute pain from episodic vaso-occlusion (VOC) spans the lifespan of almost everyone with sickle cell disease (SCD), while additional chronic pain develops in susceptible individuals in early adolescences. Frequent acute pain with chronic pain causes significant physical and psychological morbidity, and frequent health-care utilization. Available pharmacologic therapies reduce acute pain frequency but few evidence-based therapies are available for chronic pain. Areas covered: An extensive PubMed literature search was performed with appropriate search criteria. The pathophysiology of acute pain from VOC in SCD is very complex with many events subsequent to sickle polymer formation. Sensitization of pain pathways and alterations of brain networks contributes to the experience of chronic pain. Numerous therapies targeting putative VOC mechanisms are in clinical trials, and show considerable promise. Alternative analgesic treatments for acute and chronic pain have been examined in small patient cohorts, but formal clinical trials are lacking. Expert opinion: Childhood is likely a critical window for prevention of acute and later chronic pain. New multimodal analgesic therapies are needed, particularly for chronic pain, and should be examined in clinical trials. Given the multifactorial nature of both pain and VOC, simultaneously targeting multiple mechanisms may be the optimal approach for effective preventive therapies.

Defining trajectories of acute pain in surgical patients short title: acute pain follow-up.

INTRODUCTION: Assessment of acute postoperative pain is mandatory for effective treatments. Pain trajectories may help professionals improve treatments. It has been suggested that uncontrolled pain in the immediate postoperative period generates higher pain intensities on the following days of hospital stay. OBJECTIVE: To determine the relationship between pain during the first postoperative hour and the first 24 postoperative hours. METHODS: Setting: a general university hospital. Study design: a prospective observational, analytical study of patients undergoing surgical procedures under general anesthesia and hospitalized for at least 24 hours. Five assessments of pain were carried out during the first hour in the recovery room followed by three assessments during the first 24 hours. The slopes of pain trajectories were calculated, and the relationship between them was analyzed. RESULTS: 234 patients were recruited, 31.3% had uncontrolled pain on arrival at the recovery room; at the end of the first 24 hours after surgery, 5.5% of the patients had uncontrolled pain. The first pain intensity score in the recovery room correlated negatively with the slope for the first hour (P1): rS = -0.657 (p = 0.000). Similarly, the first pain intensity score had a negative association with the pain trajectory slope during the hospital stay (P2): rS = -0.141 (p = 0.032). When comparing the two slopes, a nonsignificant negative correlation was found: rS = -0.126. CONCLUSIONS: the trajectory of pain during the first hour does not predict the behavior of the trajectory during the first day after surgery.

Fatores biopsicossociais associados com a incapacidade em idosos com dor lombar aguda: estudo BACE-Brasil / Biopsychosocial factors associated with disability in older adults with acute low back pain: BACE-Brasil study

Resumo Este estudo transversal avaliou a associação de fatores biopsicossociais com a incapacidade em idosos com um novo episódio de dor lombar aguda. Foram incluídos idosos com um novo episódio de dor lombar aguda e excluídos aqueles com alterações cognitivas e deficiências motoras graves. A incapacidade foi avaliada pelo Roland Morris Disability Questionnaire. Os fatores biopsicossociais (variáveis clínicas, funcionais, estado de saúde, psicológicas e sociais) foram avaliados por um questionário estruturado multidimensional e exame físico. Regressão linear multivariada foi utilizada para análise dos dados com significância estatística de 0,05. Participaram 386 idosos com média de idade de 71,6 (±4,2) anos e incapacidade de 13,7 (±5,7) pontos. A análise de regressão linear multivariada identificou que pior saúde física e mental (avaliados através do SF-36), baixa autoeficácia em quedas, dificuldade para dormir por causa da dor, piores níveis de cinesiofobia, maiores índices de massa corporal, presença de rigidez matinal na coluna lombar, maior intensidade de dor, sexo feminino e pior mobilidade funcional foram significativamente associados com incapacidade (p < 0,05). Incapacidade relacionada à dor lombar está significativamente associada com piores condições biopsicossociais de saúde em idosos.

Abstract This cross-sectional study evaluated the association of biopsychosocial factors with disability in older adults with a new episode of acute low back pain. Older patients with a new episode of acute low back pain were included and those with cognitive alterations and severe motor impairment were excluded. Disability was assessed using the Roland Morris Disability Questionnaire. The biopsychosocial factors (clinical, functional, health status, psychological and social variables) were evaluated by a structured multidimensional questionnaire and physical examination. A multivariate linear regression was used to analyze data with a statistical significance of 0.05. A total of 386 older individuals with a mean age of 71.6 (± 4.2) years and disability of 13.7 (± 5.7) points were enrolled. Our regression analyses identified that worse physical and mental health (assessed through SF-36), low falls self-efficacy, trouble sleeping due to pain, worse kinesiophobia levels, higher body mass indexes, lumbar morning stiffness, increased pain intensity, female gender and worse functional mobility were significantly associated with baseline disability (p < 0.05). Low back pain-related disability is significantly associated with worse biopsychosocial health conditions in older adults.

Defining trajectories of acute pain in surgical patients short title: acute pain follow-up

SUMMARY INTRODUCTION: Assessment of acute postoperative pain is mandatory for effective treatments. Pain trajectories may help professionals improve treatments. It has been suggested that uncontrolled pain in the immediate postoperative period generates higher pain intensities on the following days of hospital stay. OBJECTIVE: To determine the relationship between pain during the first postoperative hour and the first 24 postoperative hours. METHODS: Setting: a general university hospital. Study design: a prospective observational, analytical study of patients undergoing surgical procedures under general anesthesia and hospitalized for at least 24 hours. Five assessments of pain were carried out during the first hour in the recovery room followed by three assessments during the first 24 hours. The slopes of pain trajectories were calculated, and the relationship between them was analyzed. RESULTS: 234 patients were recruited, 31.3% had uncontrolled pain on arrival at the recovery room; at the end of the first 24 hours after surgery, 5.5% of the patients had uncontrolled pain. The first pain intensity score in the recovery room correlated negatively with the slope for the first hour (P1): rS = −0.657 (p = 0.000). Similarly, the first pain intensity score had a negative association with the pain trajectory slope during the hospital stay (P2): rS = −0.141 (p = 0.032). When comparing the two slopes, a nonsignificant negative correlation was found: rS = −0.126. CONCLUSIONS: the trajectory of pain during the first hour does not predict the behavior of the trajectory during the first day after surgery.

RESUMO INTRODUÇÃO: A avaliação da dor pós-operatória aguda é obrigatória para tratamentos eficientes. As trajetórias da dor podem ajudar os profissionais a melhorar os tratamentos. Tem sido sugerido que a falta de controle da dor no período pós-operatório imediato vai gerar maior intensidade dessa dor durante os dias seguintes de estadia no hospital. OBJETIVO: Determinar o relacionamento entre a dor durante a primeira hora pós-operatória e as 24 horas após a mesma. MÉTODOS: Lugar da pesquisa: Hospital universitário geral. Desenho do estudo: Foi feito um estudo analítico prospectivo operacional com pacientes submetidos a procedimentos cirúrgicos sob anestesia geral e que foram hospitalizados pelo menos 24 horas antes. Cinco avaliações de dor foram feitas na primeira hora na sala de recuperação, seguidas de três avaliações durante as primeiras 24 horas. Os declives das trajetórias da dor foram calculados e seu relacionamento entre elas foi analisado. RESULTADOS: Duzentos e trinta e quatro pacientes foram recrutados, 31,3% apresentaram dor não controlada no ingresso à sala de recuperação; no final das primeiras 24 horas após a cirurgia, 5,5% dos pacientes apresentaram dor não controlada. O score da primeira intensidade de dor na sala de recuperação teve uma correlação negativa com o declive da primeira hora (P1): rS = −0,657 (p=0,000). De maneira similar, o score na primeira intensidade de dor teve uma associação negativa com o declive da trajetória da dor durante a permanência no hospital (P2): rS = −0,141 (p=0,032). Quando comparados os dois declives, não foi encontrada uma correlação significativa: rS = −0,126. CONCLUSÃO: A trajetória da dor durante a primeira hora não prediz o comportamento da trajetória durante o primeiro dia após a cirurgia.

The Effect of Induced and Chronic Pain on Attention.

Pain has well-established effects on attention. At present, parallel literatures exist that have examined the effects of experimentally induced pain and consider cognitive performance in patients with chronic pain states. However, no study to date as attempted to examine the combined or differing effects of these 2 manifestations of pain in a single study. Twenty-four participants with fibromyalgia (aged 43.00 ± 28.28 years) and 26 healthy controls (aged 36.07 ± 11.93 years) completed an n-back task, an attentional switching task, and a divided attention task, once during induced, moderately intense pressure pain, and once without induced pain. Pain induction had selective effects on the n-back task and an overall decrease in accuracy on the attentional switching task. Conversely, patients with fibromyalgia were selectively impaired in performance on the divided attention task. These data therefore suggest that the effects of pain are not summative and rather that the mechanisms that underlie the negative effects of pain on performance in acute and chronic states may differ. More research is needed to examine these mechanisms and how these negative effects can be ameliorated to treat cognitive symptoms in pain. PERSPECTIVE: This article presents a study to examine the effects of an acute, induced pain model on cognitive performance in both patients with fibromyalgia and healthy control populations. We established that the effects of acute and chronic pain on attention are different, suggesting that different models need to be developed to understand these phenomena.

Acute postoperative pain exacerbates neuroinflammation and related delirium-like cognitive dysfunction in rats.

The acute neuroinflammatory response to surgery may play a key pathogenic role in postoperative delirium (POD). Here, we investigated the contribution of acute postoperative pain to neuroinflammation and related delirium-like behaviors after surgery in adult and aged rats. Animals were assigned into four groups: control, abdominal surgery, surgery with analgesia using local ropivacaine, and surgery with analgesia using systemic morphine. Pain was assessed by the Rat Grimace Scale (RGS). Trace and context memory retention was evaluated following trace fear conditioning during the first 2 days after surgery. Pro-inflammatory cytokines in medial prefrontal cortex and hippocampus were measured by enzyme-linked immunosorbent assay. In both age groups, the RGS increased significantly from baseline until 6 h after surgery. The postoperative analgesia with either local or systemic regimens comparably alleviated the RGS increase in adult and aged animals. The two analgesic regimens attenuated the surgery-induced trace and context memory deficits, as well as cytokines overproduction in both medial prefrontal cortex and hippocampus. No age-related differences were found in the neuro-cognitive effectiveness of postoperative analgesia. Our experimental findings provide proof-of-concept for adequate postoperative pain management as one of the main preventive strategies of POD.

A fixed nitrous oxide/oxygen mixture as an analgesic for trauma patients in emergency department: study protocol for a randomized, controlled trial.

BACKGROUND: Acute pain is always the most common complaint in Emergency Department admissions and options for analgesia are limited. Nitrous oxide/oxygen possess many properties showing it may be an ideal analgesic method for the Emergency Department; it is quick-acting, well-tolerated, and does not mask signs and symptoms. The aim of this study is to evaluate the safety and analgesic effect of the fixed nitrous oxide/oxygen mixture for trauma patients in a busy emergency environment. METHODS: The randomized, double-blind, prospective, placebo-controlled study will be carried out in the Emergency Department of General Hospital of Ningxia Medical University. The target research objects are trauma patients who present to the Emergency Department and report moderate to severe intensities of acute pain. A total of 90 patients will be recruited and randomly assigned into the treatment and control group. The treatment group will receive conventional pain treatment plus nitrous oxide/oxygen mixture and the control group will receive conventional pain treatment plus oxygen. Neither patients, nor investigators, nor data collectors will know the nature of the gas mixture in each cylinder and the randomization list. Outcomes will be monitored at baseline(T0), 5 min (T1), and 15 min (T2) after the beginning of intervention and at 5 min post intervention (T3) for each group. The primary outcome is the level of pain relief after the initial administering of the intervention at T1, T2, and T3. Secondary outcomes include adverse events, physiological parameters, total time of the gas administration, satisfaction from both patients and healthcare professionals, and the acceptance of patients. DISCUSSION: Our previous studies suggested that a fixed nitrous oxide/oxygen mixture was an efficacious analgesic for the management of burning dressing pain and breakthrough cancer pain. The results of this study will provide a more in-depth understanding of the effect of this gas. If this treatment proves successful, it could help to generate preliminary guidelines and be implemented widely in trauma patients with pain in Emergency Departments. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-INR-16007807 . Registered on 21 January 2016.

Mechanisms of acute and chronic pain after surgery: update from findings in experimental animal models.

PURPOSE OF REVIEW: Management of postoperative pain is still a major issue and relevant mechanisms need to be investigated. In preclinical research, substantial progress has been made, for example, by establishing specific rodent models of postoperative pain. By reviewing most recent preclinical studies in animals related to postoperative, incisional pain, we outline the currently available surgical-related pain models, discuss assessment methods for pain-relevant behavior and their shortcomings to reflect the clinical situation, delineate some novel clinical-relevant mechanisms for postoperative pain, and point toward future needs. RECENT FINDINGS: Since the development of the first rodent model of postoperative, incisional pain almost 20 years ago, numerous variations and some procedure-specific models have been emerged including some conceivably relevant for investigating prolonged, chronic pain after surgery. Many mechanisms have been investigated by using these models; most recent studies focussed on endogenous descending inhibition and opioid-induced hyperalgesia. However, surgical models beyond the classical incision model have so far been used only in exceptional cases, and clinical relevant behavioral pain assays are still rarely utilized. SUMMARY: Pathophysiological mechanisms of pain after surgery are increasingly discovered, but utilization of pain behavior assays are only sparsely able to reflect clinical-relevant aspects of acute and chronic postoperative pain in patients.

Acute and chronic pain affects local field potential of the medial prefrontal cortex in different band neural oscillations.

The medial prefrontal cortex is involved in the process of sensory discrimination. In this study, we examined the local field potential activity response to the different stages of pain in the prelimbic cortex (PrL) which is a sub-region of the medial prefrontal cortex. Recent studies revealed extensive information about neural oscillations, but there is limited information on the local field potential profiles for acute or chronic pain, particularly in freely moving animals. This study showed that acute mechanical pain increases alpha oscillation and decreases beta and gamma oscillations before spared nerve injury surgery. Delta oscillation was decreased by chronic pain and gamma oscillation varied with time. However, acute mechanical pain stimulus had no effects on local field potential in rats under mechanical allodynia. Together, our findings provide novel insights into the role of medial prefrontal cortex local field potential activity response to pain stimulus.