Looking Back, Moving Forward in Pain Medicine.

Pain is an ancient medical complaint and a clinical riddle that has never been entirely solved. Looking back into history was the springboard to a look into the future of pain medicine. This article was based on a series of presentations given in a recent congress (May 2023) and represents the research, views, and opinions of the authors. Opium has been used for millennia to treat pain, but when it gained broad use in the United States in the 1980s and 1990s, it was so vastly overprescribed and mis-prescribed that it led to a public health crisis. This, in turn, led to the reaction where opioids at times were under-prescribed, leaving out many patients who may have benefited from opioids while leaving many legacy pain patients to manage withdrawal on their own and with few analgesic options. Cannabinoids (CB) were likewise widely used for various conditions, including pain, but were outlawed in the 20th century, only to be brought back as a potential analgesic agent. Interventional pain medicine is a developing discipline and has reinforced the concept of the interdisciplinary pain clinic. It plays an increasingly important part in modern medicine overall, especially with the support of ultrasound, for both diagnosis and therapy. Today, the views about pain have changed. Anyone has accepted that pain is not purely a physical phenomenon but a biopsychosocial phenomenon that occurs within a cultural context. Pain management remains a small but vitally important medical subspecialty that is critical from a functional enablement and population health perspective, which is helping to navigate new therapeutic targets, new drugs and routes of administration, greater understanding of pain psychology, and new technologies. Pain control today means early intervention, functional enablement through pain alleviation, educating patients about pain management, and minimizing the transition from acute to chronic pain.

Advances in the Management of Acute Postsurgical Pain: A Review.

Despite the millions of surgeries performed every year around the world, postoperative pain remains prevalent and is often addressed with inadequate or suboptimal treatments. Chronic postsurgical pain is surprisingly prevalent, and its rate varies with the type of surgery, as well as with certain patient characteristics. Thus, better clinical training is needed as well as patient education. As pain can be caused by more than one mechanism, multimodal or balanced postsurgical analgesia is appropriate. Pharmacological agents such as opioid and nonopioid pain relievers, as well as adjuvants and nonpharmacologic approaches, can be combined to provide better and opioid-sparing pain relief. Many specialty societies have guidelines for postoperative pain management that emphasize multimodal postoperative analgesia. These guidelines are particularly helpful when dealing with special populations such as pregnant patients or infants and children. Pediatric pain control, in particular, can be challenging as patients may be unable to communicate their pain levels. A variety of validated assessment tools are available for diagnosis. Related to therapy, most guidelines agree on the fact that codeine should be used with extreme caution in pediatric patients as some may be "rapid metabolizers" and its use may be life-threatening. Prehabilitation is a preoperative approach that prepares patients in advance of elective surgery with conditioning exercises and other interventions to optimize their health. Prehabilitation may have aerobic, strength-training, nutritional, and counseling components. Logistical considerations and degree of patient adherence represent barriers to effective prehabilitation programs. Notwithstanding all this, acute postoperative pain represents a clinical challenge that has not yet been well addressed.

Play as a Stress-Coping Method Among Children in Light of the COVID-19 Pandemic: A Review.

The COVID-19 pandemic, which started in early 2020, has been a great source of stress for almost every person all around the world. However, this is particularly true for children. It is necessary to fully address the stress-related psychosocial issues connected with the pandemic, solely in children. Play is important for children's development, as it is a natural activity for every child. Through play and play-based interventions, children can communicate non-verbally, symbolically, and in an action-oriented manner. Therefore, play-based interventions may have the potential to be one of the coping strategies used by children who experience stress, especially during the COVID-19 pandemic. The aim of this narrative review was to show how play-based activities could help children deal with stress related to the COVID-19 pandemic in the non-clinical population. A systematic search of the literature in various databases was performed. The initial search provided 5,004 potentially eligible studies in various databases, and 42,201 records identified from Google Scholar. After excluding studies not meeting the inclusive criteria, nine papers were selected for this narrative review. This narrative review showed findings that play-based activities can have a positive effect during the COVID-19 pandemic on different stress levels in the children population. Additionally, the findings of this review highlight the importance of further research and implementation of play into many aspects of children's life.

Answering Big Questions in Pain Medicine.

The future of pain medicine is marked by many questions. What can other nations around the world learn from the opioid crisis that is still affecting the United States? The American opioid experience was mischaracterized and wrongly described, and its causes were misdiagnosed from the outset, leading to its mismanagement and the abandonment of many chronic pain patients to their suffering. There are a few new drugs in the analgesic armamentarium. What new targets do we have in pain medicine? There are many breakthroughs, discoveries, and potential new targets that could add to our analgesic prescribing choices. These include sigma receptors, d-amino acid oxidase, endoplasmic reticulum stress receptors, histone deacetylase, and others. Neuromodulation had been used with varying degrees of success for years, but with a simplistic approach based on the gate theory of pain. Despite our familiarity with neuromodulation and spinal cord stimulators, neuromodulation research indicates that the activation of glial cells may activate the immune system and enhance analgesia. Neuromodulation studies have concentrated on how electricity affects neuronal activity rather than how electrical activity could reduce pain. There are still more frontiers in our battle against pain and some promising avenues for treatments. This narrative review will try to summarize what can be done from the perspective of recent technological and pharmacological developments.

Cognitive-Behavioral Play Therapy and COVID-19 Pandemic Trauma in Preschool Children.

Traumatic life events, such as the ongoing COVID-19 pandemic, can be a challenging health emergency, among others. The pandemic can also affect young preschoolers. They can experience negative emotions and behavioral and social difficulties. It can be hard for children to understand on their own what is going on, as well as for their families. This narrative review summarizes the role of psychotherapeutic approaches in working with trauma and aims to manage trauma, such as COVID-19, in preschool children. It focuses on the possibilities of applying cognitive-behavioral play therapy (CBPT) in preschool children who suffer from trauma during the COVID-19 pandemic period. The therapeutic approaches are tailored to specific development in preschoolers. Furthermore, the article provides insights into the relationship between negative emotions, thinking, and behavior, and COVID-19 as a threat, by describing a cognitive model in preschool-aged children. Finally, the article offers possible ways of applying play-based cognitive-behavioral therapy programs in preschool children who are victims of trauma.

One-Step Nucleic Acid Amplification System in Comparison to the Intraoperative Frozen Section and Definitive Histological Examination Among Breast Cancer Patients: A Retrospective Survival Study.

Simple Summary: Implementing intraoperative assessment of sentinel lymph nodes by one-step nucleic acid amplification in early breast cancer can reduce the surgical burden to the patient and the costs to the health system. However, only limited data are available in terms of long-term disease-free survival and overall survival. Therefore, this study aims to compare disease-free survival and overall survival between one-step nucleic acid amplification, frozen section, and definitive histology. These results could impact the healthcare community, adding further proof to the body of evidence supporting the broader adoption of this innovative technology that enables a safe reduction in patient surgical burden and healthcare costs. Background: The one-step nucleic acid amplification (OSNA) system is a novel molecular technique, which consents to quick intraoperative detection of sentinel lymph node metastases by the amplification of cytokeratin 19 mRNA. Our study aims to evaluate the OSNA method in comparison with frozen section (FS) and definitive histological examination of the sentinel lymph node biopsy among early breast cancer patients considering disease-free survival (DFS) and overall survival (OS). Methods: In this study, we included all women who underwent sentinel lymph node biopsy (SLNB) for breast cancers classified as TNM stage I and II in our center between January 2005 and January 2017, and the follow-up was collected up to January 2019. We divided patients among three groups based on SLNB evaluation: definitive histological examination, intra-operative FS, or OSNA. Results: We included 2412 SLNBs: 727 by definitive histological examination, 697 by FS, and 988 by OSNA. Isolated tumor cells were found in 2.32% of cases, micrometastasis in 9.12%, and macrometastases in 13.64%. Surgical procedure duration was significantly shorter in OSNA than in FS (42.1 minutes ±5.1 vs. 70.1 minutes ±10.5, p <0.05). No significant differences have been observed among the three groups regarding OS, DSF, cumulative local, or distant metastases. In particular 5-year DFS was 96.38% in definitive histology (95% C.I. 95.02-97.75%), 96.37% in FS (95% C.I. 94.98-97.78%), and 96.51% in OSNA group (95% C.I. 95.32-97.72%). Conclusions: No difference in OS and DFS was found comparing OSNA, FS, and definitive histology. Furthermore, reduced operative time was found in the OSNA group.

Neuromodulation for Pain Management in the Inpatient Setting: A Narrative Review.

Pain is highly prevalent and pharmacological therapy is not always efficacious. There are a few pathophysiological reasons to believe that neuromodulation would increase the rate of success of pain management. This review article is focused on that aspect, discussing non-invasive or minimally invasive neuromodulation techniques in both the inpatient and outpatient setting. This article provides an in-depth discussion of the multiple neuromodulation techniques available over time to be suitable and effective when used as analgesic therapies for chronic pain. We reviewed the literature and discussed all available neuromodulation options that were tested in the inpatient and outpatient setting. Neuromodulation plays a very important role in treating chronic pain in both inpatient and outpatient setting.

Vasopressor-Sparing Action of Methylene Blue in Severe Sepsis and Shock: A Narrative Review.

Shock is a serious acute circulatory failure leading to inadequate oxygen delivery to the cells. Its treatment is mainly based on circulating fluid optimization, and vasopressors to provide an adequate mean arterial pressure and microcirculatory flow. Norepinephrine is the drug of choice, but high dosages may be responsible for several side effects, including increased myocardial oxygen consumption, dysrhythmias, and peripheral and organ ischemia. Moreover, some patients are "non-responders" to first-line norepinephrine treatment. Hence, other drugs have been proposed to reach and maintain the hemodynamic target. In general, they are described as catecholamine-sparing agents. Among others, the most used are vasopressin, corticosteroids, and angiotensin II. Methylene blue (MB) represents a further option, even though its use is still a topic of controversy. This review article tries to summarize what is known and unknown about the actions of MB in patients in shock. It reduces excessive production of nitric oxide via blockade of guanylate cyclase in shock states. At present, it appears the MB provides positive results in septic shock, if administered early. Further randomized controlled trials are warranted regarding its use to provide more precise indications to physicians involved in the treatment of such patients.

Epidural Corticosteroids, Lumbar Spinal Drainage, and Selective Hemodynamic Control for the Prevention of Spinal Cord Ischemia in Thoracoabdominal Endovascular Aortic Repair: A New Clinical Protocol.

INTRODUCTION: In patients undergoing thoracoabdominal aorta repair, spinal cord ischemia (SCI) remains one of the most common and important complications resulting in transient paraparesis through to permanent flaccid paraplegia. In this manuscript, after a brief introduction to spinal cord ischemia complication and its prevention in thoracoabdominal endovascular aortic repair (TEVAR), we propose a new clinical protocol potentially able to prevent such complication. METHODS: The proposed protocol suggests the use of high dosages of corticosteroids by epidural route, along with drainage of cerebrospinal fluid and controlled vascular hypertension, to reduce the incidence of SCI in TEVAR. Moreover, we paid particular attention to the control of the hemodynamic parameters to obtain adequate peripheral tissue perfusion (oxygen delivery), including in the spinal cord. RESULTS: We applied this new protocol in 50 consecutive patients treated with TEVAR for thoracoabdominal aortic aneurysms (TAAs); 47 patients completed the procedure: 27 patients Crawford type I and 20 Crawford type II. Three patients died during surgery because of untreatable aneurysm rupture. The results show that in all patients there were no cases of SCI, after 5 days from TEVAR. DISCUSSION: To the best of our knowledge, there are no clinical studies on the use of epidural corticosteroids in patients undergoing treatment of aortic syndrome (both in "open surgery" and endovascular aortic repair). This initial study on 50 consecutive patients has shown that the clinical protocol used could be of great interest to prevent one of the worse complications of TEVAR. Its limitations are the low number of patients studied till now, and the non-randomized protocol adopted. Further studies would be necessary. CONCLUSION: Our experience and the results obtained with this new perioperative protocol with epidural corticosteroid and accurate hemodynamic control have been encouraging and it seems a valid proposal to be explored in future by well-structured prospective, randomized protocols.

Long term results of hepatic resection or orthotopic liver transplantation in patients with liver metastases from gastrointestinal neuroendocrine tumors.

Hepatic metastases are one of the most important prognostic factors for survival among patients affected by gastrointestinal neuroendocrine tumors (NETs). The present study aims to evaluate the impact of surgery, including hepatic resection or orthotopic liver transplantation (OLT), on the outcome of patients affected by hepatic metastases from NETs, in terms of overall survival (OS). In this multicentric retrospective study, data was collected on 26 patients, who underwent surgery for hepatic metastases from NETs in two Italian University Clinics between January 1990 and December 2012; of which, 22 patients underwent hepatic resective surgery and 4 patients OLT. Hepatic metastases were synchronous in the 53.8% of cases and metachronous in the 46.2% of cases. The median number of resected hepatic metastases was 3. Surgical radicalness (R0) was reached in the 84.6% of cases. In total, 57.7% of patients had a recurrence, 66.7% of which were intra- and 33.3% extra-hepatic. The OS of patients that underwent hepatic resections and OLT was 44.9% [95% confidence interval (CI95), 26.0-77.7%] and 50% (CI95, 12.5-100.0%) at 5 years, respectively. Although the data regarding the survival of patients receiving surgery for hepatic metastases from NETs are encouraging, randomized clinical trials are necessary to more adequately evaluate the effect of surgery on survival of this group of patients.

Pros and cons of liver transplantation in human immunodeficiency virus infected recipients.

Before the introduction of combined highly active antiretroviral therapy, a positive human immunodeficiency virus (HIV) serological status represented an absolute contraindication for solid organ transplant (SOT). The advent of highly effective combined antiretroviral therapy in 1996 largely contributed to the increased demand for SOT in HIV-positive individuals due to increased patients' life expectancy associated with the increasing prevalence of end-stage liver disease (ESLD). Nowadays, liver failure represents a frequent cause of mortality in the HIV-infected population mainly due to coinfection with hepatitis viruses sharing the same way of transmission. Thus, liver transplantation (LT) represents a reasonable approach in HIV patients with stable infection and ESLD. Available data presently supports with good evidence the practice of LT in the HIV-positive population. Thus, the issue is no longer "whether it is correct to transplant HIV-infected patients", but "who are the patients who can be safely transplanted" and "when is the best time to perform LT". Indeed, the benefits of LT in HIV-infected patients, especially in terms of mid- and long-term patient and graft survivals, are strictly related to the patients' selection and to the correct timing for transplantation, especially when hepatitis C virus coinfection is present. Aim of this article is to review the pros and cons of LT in the cohort of HIV infected recipients.

Feasibility of concervative breast surgery and intraoperative radiation therapy for early breast cancer: a single-center, open, non-randomized, prospective pilot study.

Intraoperative radiotherapy (IORT) consists of an accelerated, single-dose, partial breast irradiation, performed immediately after breast conservative surgery. In the present study, we report the results of our feasibility protocol study using IORT between 2005 and 2009. We analyzed the data from a single-center, open, non-randomized, prospective pilot study including patients who underwent breast conservative surgery for invasive breast cancer between January 2005 and December 2009 at our Clinic of Surgery. Patients were divided based on IORT performance and stratified by age (≥48 or <48 years). Data were analyzed using R (version 2.15.2), considering a level of significance at p<0.05. Among the 247 eligible patients, 81 accepted the IORT protocol. Intraoperative IORT feasibility was 95.1% (77/81). In 71.4% (55/77) of the cases no postoperative complication was registered. Concerning local recurrence and overall survival, no significant difference was observed between women who underwent the IORT protocol or standard treatment. Among the patients aged <48 years, no local recurrence was noted after IORT protocol, and among women aged ≥48, local recurrences developed later in patients treated with IORT than with standard treatment. IORT represents a feasible and promising technique for the treatment of early breast cancer, with low morbidity, and beneficial aesthetic and oncologic results. Further studies are required in order to extend the inclusion criteria and offer IORT to a larger number of breast cancer patients.

Acute pain and availability of analgesia in the prehospital emergency setting in Italy: a problem to be solved.

OBJECTIVES: The treatment of acute pain in the prehospital emergency setting remains a significant problem. We evaluated the incidence, site, and possible cause of acute pain in the prehospital period and also the current state of prehospital pain management by evaluating analgesic availability in emergency vehicles in Italy. METHODS: First aid volunteers documented the presence, intensity, and site of acute pain by questionnaire for over 3 months. Emergency service operations completed a questionnaire on analgesic availability in ambulances and helicopters. RESULTS: Pain symptoms were present in two-thirds of the patients (n = 383) and ranked as moderate to unbearable in 41.75%. Results of the analgesic availability survey indicate that 10.6% of the ambulance services carry no pain killers (including non-steroidal anti-inflammatory drugs [NSAIDs] and/or paracetamol) and 11.5% are without an opioid. The emergency helicopter survey showed a significant difference in analgesic availability compared with ambulances, with 97.6% having at least one opioid agent available (weak or strong). A wide geographical variation in the availability of analgesic agents in ambulance and helicopter services was seen. CONCLUSIONS: There is a high prevalence of pain among patients receiving prehospital emergency treatment in Italy and treatment for acute pain during emergency treatment of trauma patients is inadequate. All emergency vehicles, without distinction, should carry opioids and other analgesic drugs (NSAIDs and paracetamol) and there should be no geographic differences in the availability of pain medications.

Epidural local anesthetic plus corticosteroid for the treatment of cervical brachial radicular pain: single injection versus continuous infusion.

BACKGROUND: Efficacy of epidural local anesthetics plus steroids for the treatment of cervicobrachial pain is uncertain. METHODS: A prospective study randomized 160 patients with cervicobrachial pain resistant to conventional therapy. Patients were divided into 4 groups on the basis of the time between pain onset and treatment initiation: group A, 40 patients with pain onset 15 to 30 days; group B, 40 patients with pain from 31 to 60 days; group C, 40 patients, 61 to 180 days; and group D, 40 patients with pain >180 days. Patients of each group were randomized to receive an epidural block with bupivacaine and methylprednisolone at intervals of 4 to 5 days (Single injection) or continuous epidural bupivacaine every 6, 12, or 24 hours plus methylprednisolone every 4 to 5 days (Continuos epidural). The maximum duration of treatment (9 blocks in Single injection, and 30 days in Continuos epidural) was dependent on achieving Pain Control (PC) > or =80% [PC is defined by this formulae: (100) (VAS(initial)-VAS(final))/VAS(initial)]. Follow-up at 1 month and 6 months compared PC and the number of pain-free hours of sleep. RESULTS: One hundred forty-one patients completed the study. The 4 groups had similar characteristics. At the 1-month and 6-month follow-up analysis based on the time between pain onset and treatment initiation showed that patients of group D, who received the Continuous epidural treatment, had significantly greater PC and significantly more pain-free hours of sleep compared with similar patients in Single injection. CONCLUSIONS: Therapy with continuous epidural local anesthetic and methylprednisolone provides better control of chronic cervicobrachial pain compared with Single injection. These results are discussed with respect to the possible mechanism of action of the drugs and may relate to the physiopathologic mechanisms associated with neuronal plasticity that result in chronic pain.