The Importance of the Treatment Rationale for Pain in Animal-Assisted Interventions: A Randomized Controlled Trial in Healthy Participants.

Animal-assisted interventions (AAIs) is a promising treatment approach for pain, but possible mechanisms still need to be elucidated. This study set out to investigate the analgesic effects of an animal provided with a treatment rationale in a randomized controlled trial employing a standardized experimental heat-pain paradigm. We randomly assigned 128 healthy participants to: dog treatment (DT), placebo treatment (PT), dog and placebo treatment (DPT), and no treatment (NT). Primary outcomes were heat-pain tolerance and the corresponding self-reported ratings of pain unpleasantness and intensity. Results revealed no differences in heat-pain tolerance between the conditions. However, participants in the DT condition experienced heat-pain as significantly less unpleasant at the limit of their tolerance compared to participants in the NT condition (estimate = -0.96, CI = -1.58 to 0.34, P = .010). Participants in the DT condition also showed lower ratings of pain intensity at the limit of their tolerance compared to participants in the NT condition (estimate = -0.44, CI = -0.89 to 0.02, P = .060). This study indicates that a dog has analgesic effects on pain perception when integrated into the treatment rationale. We assume that providing a treatment rationale regarding the animal is important in AAIs for pain. PERSPECTIVE: This study shows that the presence of an animal is not sufficient for animal-assisted interventions (AAIs) to have an analgesic effect on pain unless they are provided with a treatment rationale. This could imply that not only the animal but also contextual factors are important in AAIs. TRIAL REGISTRATION: Clinical Trials NCT04361968.

Chronic pain and continuity of analgesic treatment during the COVID-19 pandemic.

INTRODUCTION: Chronic pain can trigger both physical and mental health complications. During the COVID-19 pandemic, patients with chronic diseases have had reduced access to some medications. OBJECTIVE: To determine the pharmacological management of patients with chronic pain and its continuity during the COVID-19 pandemic. METHODS: This was a retrospective longitudinal study of the continuity of analgesic use in patients with chronic pain between September 1, 2019 and February 28, 2021 based on a drug dispensing database. Survival analysis was performed until the discontinuation of chronic analgesics. RESULTS: A total of 12,701 patients who were being treated for chronic pain were identified. Their median age was 70.3 years, and 74.4% were women. The pain of rheumatological origin was the most frequent etiology (46.1%); the most used medications were nonopioid analgesics (78.9%), pain modulators (24.8%) and opioid analgesics (23.3%). A total of 76.1% of the patients experienced interruptions in their management during the study period. The median time to the first interruption of treatment was 5.0 months (95% CI: 4.8-5.2). Those who were treated for oncological pain experienced a greater number of interruptions in their management. CONCLUSIONS: The pharmacological management of patients with chronic pain is heterogeneous, and this real-world study showed that a high proportion of patients experienced an interruption of pain management during the 12 months following the onset of the COVID-19 pandemic.

Impact of COVID-19 Pandemic Lockdown on Migraine Patients in Latin America.

The coronavirus (COVID-19) pandemic, confinement, fear, lifestyle changes, and worldwide health care impacted almost all diseases. Reports from countries outside Latin America revealed differences in migraine patients. In this study, we describe and compare the immediate changes in migraine symptoms associated with COVID-19 quarantine in patients from Argentina, Mexico, and Peru. An online survey was conducted from May to July 2020. The survey was answered by 243 migraine patients, with questions related to sociodemographic data, quarantine conditions, changes in working conditions, physical activity, coffee intake, healthcare access, acute migraine medication use, symptoms of anxiety, depression, and fear of COVID-19. The results show that 48.6% of migraine patients experienced worsened symptoms, 15.6% improved, and 35.8% remained unchanged. Worsening migraine symptoms were associated with staying at home during the lockdown. Intake of analgesics was associated with an increase in migraine symptoms of 18 times relative to those who did not increase their intake. Migraine symptoms improved when the number of sleep hours was increased, and we observed an improvement when patients decreased analgesic intake. The uncertainty about the end of the pandemic, the news, and social media are three items that contributed to the worsening of migraine symptoms in patients in the three investigated countries. Confinement during the first pandemic wave in Latin America harmed migraine patients who stayed home during the lockdown.

Modulation of transient receptor potential (TRP) channels by plant derived substances used in over-the-counter cough and cold remedies.

BACKGROUND: Upper respiratory tract infections (URTIs) impact all age groups and have a significant economic and social burden on society, worldwide. Most URTIs are mild and self-limiting, but due to the wide range of possible causative agents, including Rhinovirus (hRV), Adenovirus, Respiratory Syncytial Virus (RSV), Coronavirus and Influenza, there is no single and effective treatment. Over-the-counter (OTC) remedies, including traditional medicines and those containing plant derived substances, help to alleviate symptoms including inflammation, pain, fever and cough. PURPOSE: This systematic review focuses on the role of the major plant derived substances in several OTC remedies used to treat cold symptoms, with a particular focus on the transient receptor potential (TRP) channels involved in pain and cough. METHODS: Literature searches were done using Pubmed and Web of Science, with no date limitations, using the principles of the PRISMA statement. The search terms used were 'TRP channel AND plant compound', 'cough AND plant compound', 'cough AND TRP channels AND plant compound', 'cough AND P2X3 AND plant compound' and 'P2X3 AND plant compound' where plant compound represents menthol or camphor or eucalyptus or turpentine or thymol. RESULTS: The literature reviewed showed that menthol activates TRPM8 and may inhibit respiratory reflexes reducing irritation and cough. Menthol has a bimodal action on TRPA1, but inhibition may have an analgesic effect. Eucalyptus also activates TRPM8 and inhibits TRPA1 whilst down regulating P2X3, aiding in the reduction of cough, pain and airway irritation. Camphor inhibits TRPA1 and the activation of TRPM8 may add to the effects of menthol. Activation of TRPV1 by camphor, may also have an analgesic effect. CONCLUSIONS: The literature suggests that these plant derived substances have multifaceted actions and can interact with the TRP 'cough' receptors. The plant derived substances used in cough and cold medicines have the potential to target multiple symptoms experienced during a cold.

Pain management recommendations during the progression of SARS-CoV-2 infection.

COVID-19, an infection caused by SARS-CoV-2, had a devastating impact on people's lives. The pandemic placed a heavy burden on healthcare systems and impacted the care of patients, including those with pain. This narrative review aims to highlight the challenges in managing pain and fever resulting from COVID-19 and pre-existing conditions, and to discuss the role of over the counter analgesics as a key part of the COVID-19 treatment regimen. As most patients with COVID-19 are being managed in the outpatient setting, lifestyle interventions and over the counter analgesics are readily available options to effectively treat pain and fever, which can help to decrease the burden on the healthcare system during the COVID-19 pandemic.

COVID-19 is an infection caused by SARS-CoV-2. The COVID-19 pandemic not only affects patient lives, but also heavily impacts healthcare systems. This review aims to discuss the available literature on how to manage pain from COVID-19 and encourage a consensus meeting for recommendations. As most patients with COVID-19 are being managed in the outpatient setting, lifestyle interventions and over the counter analgesics are readily available options to effectively treat pain and fever, which can help to decrease the demand on the healthcare system during the COVID-19 pandemic.

Tracheotomy in ventilator-dependent patients with COVID-19: a cross-sectional study of analgesia and sedative requirements.

OBJECTIVE: During March 2020 in the United States, demand for sedatives increased by 91%, that for analgesics rose by 79%, and demand for neuromuscular blockers increased by 105%, all owing to the number of COVID-19 cases requiring invasive mechanical ventilation (MV). We hypothesize that analgesic and sedative requirements decrease following tracheotomy in this patient population. METHODS: In this cross-sectional study, we conducted a retrospective chart review to identify patients with COVID-19 who underwent tracheotomy (T) at an academic medical center between March 2020 and January 2021. We used a paired Student t-test to compare total oral morphine equivalents (OMEs), total lorazepam equivalents, 24-hour average dexmedetomidine dosage in µg/kg/hour, and 24-hour average propofol dosage in µg/kg/minute on days T-1 and T+2 for each patient. RESULTS: Of 50 patients, 46 required opioids before and after tracheotomy (mean decrease of 49.4 mg OMEs). Eight patients required benzodiazepine infusion (mean decrease of 45.1 mg lorazepam equivalents. Fifteen patients required dexmedetomidine infusion (mean decrease 0.34 µg/kg/hour). Seventeen patients required propofol (mean decrease 20.5 µg/kg/minute). CONCLUSIONS: When appropriate personal protective equipment is available, use of tracheotomy in patients with COVID-19 who require MV may help to conserve medication supplies in times of extreme shortages.

Application of network composite module analysis and verification to explore the bidirectional immunomodulatory effect of Zukamu granules on Th1 / Th2 cytokines in lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Zukamu granules (ZKMG), as the preferred drug for the treatment of colds in Uygur medical theory, has been used for 1500 years. It is also widely used in China and included in the National Essential Drugs List (2018 edition). It has unique anti-inflammatory, antitussive and analgesic effects. AIM OF THE STUDY: Aiming at the research of traditional Chinese medicine (TCM) with the characteristics of overall regulation of body diseases and the immune regulation mechanism with the concept of integrity, this paper put forward the integrated application of network composite module analysis and animal experiment verification to study the immune regulation mechanism of TCM. MATERIALS AND METHODS: The active components and targets of ZKMG were predicted, and network module analysis was performed to explore their potential immunomodulatory mechanisms. Then acute lung injury (ALI) mice and idiopathic pulmonary fibrosis (IPF) rats were used as pathological models to observe the effects of ZKMG on the pathological conditions of infected ALI and IPF rats, determine the contents of Th1, Th2 characteristic cytokines and immunoglobulins, and study the intervention of GATA3/STAT6 signal pathway. RESULTS: The results of network composite module analysis showed that ZKMG contained 173 pharmacodynamic components and 249 potential targets, and four key modules were obtained. The immunomodulatory effects of ZKMG were related to T cell receptor signaling pathway. The validation results of bioeffects that ZKMG could carry out bidirectional immune regulation on Th1/Th2 cytokines in the stage of ALI and IPF, so as to play the role of regulating immune homeostasis and organ protection. CONCLUSIONS: The network composite module analysis and verification method is an exploration to study the immune regulation mechanism of TCM by combining the network module prediction analysis with animal experiments, which provides a reference for subsequent research.

GABAA receptors as targets for anaesthetics and analgesics and promising candidates to help treat coronavirus infections: A mini-review.

GABA is a major inhibitory neurotransmitter that regulates the balance between excitatory and inhibitory circuits in the human nervous system. The GABA receptors are divided into three main subtypes, GABAA , GABAB , and GABAC (also termed GABAA rho) receptors. GABAA receptors are pentameric ligand-gated ion channels widely expressed throughout the central and peripheral nervous system. The activation of GABAA receptors results in opening of an anion-selective channel that mainly gates chloride ions and allows them to flow into the neuron, causing hyperpolarization of the cell membrane that dampens neural excitability. This makes GABAA receptors critical anaesthetic and analgesic targets for existing as well as for the development of novel drugs. In this review, we first summarize the biochemical properties of GABAA receptors and the clinical anaesthetics and analgesics targeting the receptors. In a forward-looking section, we summarize the emerging role of GABAergic signalling in treatment of COVID-19 related infections. Finally, we discuss the opportunities arising from targeting specific and unique subunit interfaces for the development of novel anaesthetics and analgesics leading to more efficient therapies.

Trauma pain management in the emergency department: use of methoxyflurane as a patient-administered analgesic.

Evidence suggests that pain is highly prevalent among patients with traumatic injuries who attend emergency departments (EDs), yet accurate assessment and management of patients with acute pain can be challenging in this setting. Effective and rapid pain management is beneficial for patients and can support timely discharge from the ED, which is particularly important in the context of the coronavirus disease 2019 (COVID-19) pandemic. This article describes a service development project that introduced the use of a patient-administered analgesic, methoxyflurane, for patients with traumatic injuries with moderate to severe pain in one ED. The author outlines the benefits and rationale for using methoxyflurane as a first-line analgesic in this patient group and describes the main elements of training sessions for emergency nurses and other ED clinicians in the administration and supervision of patient-administered methoxyflurane.

Analgesic benefit of metamizole and ibuprofen vs. either medication alone: a randomized clinical trial.

BACKGROUND: Postoperative pain relief remains a key problem after surgery. Multimodal pain therapy has proven beneficial in alleviating pain to a certain extent. However, when combining non-opioids, the focus has been on NSAIDs and paracetamol, but effects of combined use are only moderate. Metamizole could be a potent adjunct, due to its preclusion in several countries, data on its combined use are sparse, despite its common use in many countries. The aim of this study was to examine whether the combination of metamizole and ibuprofen is superior in relieving postoperative pain to either drug alone. METHODS: For this randomized, placebo-controlled, cross-over study, 35 patients undergoing bilateral lower third molar extraction were randomized. Each patient received three applications of 1000 mg metamizole + 400 mg ibuprofen for surgery on one side and either 1000 mg metamizole + placebo or 400 mg ibuprofen + placebo on the other side. Pain ratings, rescue-medication (tramadol), and sleep were assessed for 18 hours. RESULTS: The combined treatment of metamizole and ibuprofen showed lower mean pain scores over 12 hours than ibuprofen (2.4±1.3 vs 3.8±1.6; P=0.005). Further, combined treatment showed lower mean pain scores over 6 hours than ibuprofen (2.0±1.2 vs. 3.1±1.6; P=0.022) or metamizole alone (2.0±1.2 vs. 3.3±1.7; P=0.015). Consumption of rescue medication was lowest in the combination-group (25% vs. 46%-metamizole; 50%-ibuprofen). The trial was stopped prematurely as the COVID-pandemic halted elective surgeries. CONCLUSIONS: Combined use enables superior pain control compared to ibuprofen after molar extraction and tends to be superior to metamizole alone. The premature study-termination may overestimate this effect.

Cancer Pain Management in French-Speaking African Countries: Assessment of the Current Situation and Research Into Factors Limiting Treatment and Access to Analgesic Drugs.

Introduction: There is a dearth of research on the incidence and treatment of cancer pain in Africa. Yet Africa, with other developing countries, accounts for more than half of all cancer diagnoses, and it is estimated that cancer incidence in Africa will double by 2030. Objectives: This research protocol outlines an approach to investigate cancer pain in French-speaking African countries. The protocol intends to determine and describe the treatment and management of cancer pain in these countries. Barriers to treating cancer pain will be explored and the results will be collated to make a series of recommendations on policy positions, regulatory frameworks and protocols. Methods: A mixed-methods, co-creation methodology has been selected to ensure the societal impact of the research outcomes. This research will use both qualitative and quantitative data collection methods and analyses. The research will begin with a review of the policies and legislation that exist in relation to cancer pain management and the use of analgesics, in each French-speaking African country. An Experts Steering Committee will then be created to provide guidance on the protocol and research design and access to participants, as well as to execute on the administration of surveys to local structures and international experts. A series of semi-structured, qualitative interviews with experts and clinicians in the field of screening and management of cancer pain and access to treatment will follow. Purposive and snowball sampling will be used to select the respondent experts. The semi-structured interviews will be conducted to determine the main trends and barriers to the treatment of cancer pain in French-speaking African countries. From this qualitative research, two surveys will be developed and then administered: one to validate the policy and regulatory context, and the other to determine experts and healthcare professionals experience and perceptions of cancer pain. Results/Conclusions: The results will be analyzed using quantitative and qualitative methods to determine themes and perceptions of cancer pain and treatment, from the policy level to the healthcare professional level. Evaluation of the results will lead to recommendations for a comprehensive framework for cancer pain treatment in French-speaking Africa.

Adjunctive Nonpharmacologic Interventions for the Management of Burn Pain: A Systematic Review.

BACKGROUND: The conventional way of treating burn victims with mainstream pain control modalities is costly and has many negative side effects. In this study, the authors aim to present the findings from the major clinical trials on three nonpharmacologic interventions-hypnosis, virtual/augmented reality, and yoga-as supplements to conventional pain regimens for burn management. METHODS: A computerized literature search was conducted of the PubMed and ClinicalTrials.gov databases in April of 2020. The online screening process was performed by two independent reviewers with the Covidence tool. The protocol was reported using the Preferred Reporting Items for Systematic Review and Meta-Analyses, and it was registered at the International Prospective Register of Systematic Reviews of the National Institute for Health Research. RESULTS: The search yielded 254 articles from 1955 to 2020. Fifty-eight studies met the authors' inclusion criteria. Yoga reduced cognitive and somatic anxiety in burn survivors, and improved body image. Virtual reality is effective in pain reduction in both the pediatric and the adult burn population, and in faster burn wound reepithelialization. Hypnosis has similar results regarding reducing pain quality and anxiety in burn patients undergoing burn wound care and dressing changes but was not found to significantly accelerate the healing process. CONCLUSIONS: Nonpharmacologic interventions are not a substitute for conventional analgesics; however, they could help patients have better control over their pain, greater self-esteem, and less postburn traumatic experiences. Burn care centers should consider nonpharmacologic interventions to improve patient satisfaction and their participation in the treatment and rehabilitation process.

Physical Compatibility of Nafamostat with Analgesics, Sedatives, and Muscle Relaxants for Treatment of Coronavirus Disease 2019.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) may require continuous administration of analgesics, sedatives, and muscle relaxants. Nafamostat has recently been reported as a therapeutic agent for COVID-19. However, there is a lack of information on the compatibility of nafamostat with the aforementioned drug classes. This study evaluated the physical compatibility of nafamostat with these drug classes. METHODS: Nafamostat was combined with 1-3 target drugs (fentanyl, morphine, midazolam, dexmedetomidine, and rocuronium). Fifteen physical compatibility tests were conducted. Nafamostat was dissolved in 5% glucose solution; the final concentration was 10 mg/mL. All other medications were diluted in 0.9% sodium chloride to obtain clinically relevant concentrations. The power of hydrogen (pH) of all medications was measured during each test. Compatibility tests were conducted with 4 test solutions in which nafamostat and the target drugs were compounded at equal volume ratios (1:1, 1:1:1, or 1:1:1:1). Visual appearance, turbidity, and pH were evaluated immediately after mixing and at 1 and 3 hours. Physical incompatibilities were defined as gross precipitation, cloudiness, appearance of the Tyndall effect, or a turbidity change of ≥0.5 nephelometric turbidity units (NTU) based on nafamostat. RESULTS: The mean pH of nafamostat was 3.13 ± 0.03. The combination of nafamostat, fentanyl, and dexmedetomidine had the highest pH (3.39 ± 0.01; 3 hours after mixing). All drugs were compatible with nafamostat until 3 hours after admixture, with a mean turbidity value of ≤0.03 NTU. CONCLUSIONS: Infusions combining nafamostat with the tested sedatives, analgesics, and muscle relaxants could be safely administered.

Evaluation of pain in patients with COVID-19.

OBJECTIVES: A new type of coronavirus outbreak has emerged in China and caused a pandemic. World Health Organization (WHO) announced the official name of this disease 'COVID-19'. The main purpose of this study is to evaluate pain in COVID-19 patients. METHODS: Patients who were followed in the ward of an infectious diseases department because of possible or confirmed COVID-19 between May and September of 2020 were included in the study. The Turkish version of the Brief Pain Inventory (BPI) was applied. Demographic features, frequency, location, the intensity of pain, and response to analgesics were analyzed. RESULTS: A total of 178 participants were included in the study. Ninety-one (51.1%) of patients had pain complaints and the mean pain score (MPS) was 2.28±2.81 over 10. Fifty-nine (56.0%) of participants with pain required analgesic therapy and 41 (80.3%) of them showed ≥50% pain relief with simple analgesics. Twelve of the remaining 18 who did not get enough pain relief with simple analgesic were taking their analgesics pro re nata (PRN) rather than around the clock (ATC). Pain frequency and intensity and mean hospitalization duration (MHD) were similar between confirmed and possible cases. CONCLUSION: Regarding the results, we conclude that pain is not one of the challenging symptoms and easily manageable in patients with a mild-moderate intensity of COVID-19. Our results were not enough to make a correlation between pain and the clinical course of the disease. Further studies are required for the evaluation of pain including patients in intensive care units.

Postoperative pain treatment after lumbar discectomy. A protocol for a systematic review with meta-analysis and trial sequential analysis.

BACKGROUND: Patients undergoing lumbar discectomy usually suffer from moderate to severe pain during the postoperative period. Multimodal, or balanced analgesia, is the leading treatment principle for managing postoperative pain. The rationale is to achieve optimal pain treatment through additive or synergistic effects of several non-opioid analgesics, and thereby, reducing the need for postoperative opioids, facilitating early mobilization and functional rehabilitation. For discectomy surgery, evidence of both the benefit and harm of different analgesic interventions is unclear. OBJECTIVES: This systematic review aims to investigate the benefits and harms of analgesic interventions in adult patients after lumbar discectomy. METHODS: This protocol for a systematic review is written according to The Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. We will search The Cochrane Library's CENTRAL, PubMed, EMBASE, and ClinicalTrails.gov for published and ongoing trials. All randomized clinical trials assessing the postoperative analgesics effect of an intervention with a control or no-intervention group undergoing lumbar discectomy will be included. Two authors will independently screen trials for inclusion using Covidence, extract data and assess the risk of bias using Cochrane's risk-of-bias 2 tool. We will analyse the data using Review Manager and Trial Sequential Analysis. Meta-analysis will be performed according to the Cochrane guidelines. We will present our primary findings in a 'summary of findings' table and evaluate the overall certainty of evidence using the GRADE approach. DISCUSSION: This systematic review will assess the benefits and harms of analgesic interventions after lumbar discectomy and have the potential to improve best practices and advance research.

Comparison of the short-term outcomes of using DST and PPH staplers in the treatment of grade III and IV hemorrhoids.

Stapled hemorrhoidopexy has a few advantages such as less postoperative pain and faster recovery compared with conventional hemorrhoidectomy. There are two major devices used for stapled hemorrhoidopexy, PPH stapler (Ethicon EndoSurgery) and DST stapler (Covidien). This study was conducted to investigate the postoperative outcomes among patients with grade III and IV hemorrhoids who underwent hemorrhoidopexy with either of these two devices. A total of 242 consecutive patients underwent stapled hemorrhoidopexy with either PPH stapler (110 patients) or DST stapler (132 patients) at a single center in 2017. We performed a retrospective case-control study to compare the short-term postoperative outcomes and the complications between these two groups. After matching the cases in terms of age, gender, and the grade of hemorrhoids, there were 100 patients in each group (PPH versus DST). There were no significant differences in the postoperative visual analog scale (VAS) score and analgesic usage. Among complications, the incidence of anorectal stricture was significantly higher in the DST group (p = 0.02). Evaluation of the mucosal specimen showed that the total surface area, the muscle/mucosa ratio and the surface area of the muscle were also significantly higher in the DST group (p = 0.03). Further analysis of the DST group demonstrated that patients with anorectal stricture after surgery are younger than patients without anorectal stricture, and higher muscle/mucosa ratio (p = 0.03) and a higher surface area of the muscle (p = 0.03) also measured in the surgical specimen. The two devices provide similar outcomes of postoperative recovery. Patients who underwent DST stapled hemorrhoidopexy had a higher incidence rate of stricture, larger area of muscle excision, and higher muscle/mucosa ratio in the surgical specimen. Further investigation is warranted for a better understanding of the correlation between muscle excision and anorectal stricture.

Two cases of severe COVID-19 in gestational week 27 and 28 respectively, after which both pregnancies proceeded to term.

COVID-19 in pregnancy increases the risk of caesarean section. We present two cases of late gestation pregnant women with severe COVID-19. Both were successfully treated with mechanical ventilation without termination of pregnancy and, following recovery from COVID-19, had vaginal deliveries at term. These two cases demonstrate the possibility of treating pregnant women with severe COVID-19 with mechanical ventilation in the late second and early third trimesters without them having a pre-term delivery. With a multidisciplinary approach, such management could avoid the maternal risks of surgery during a severe infection and, at the same time, enable term birth with a lower risk of neonatal complications.