Update on Overactive Bladder Therapeutic Options.

BACKGROUND: Millions of Americans are burdened by overactive bladder (OAB) syndrome and the psychogenic and economic hardships that accompany it. Several theories attempt to explain OAB as a neurogenic dysfunction, myogenic dysfunction, urothelial dysfunction, or decreased expression of a channel protein secondary to bladder outlet obstruction. Given that the etiology of OAB is a working theory, the management of OAB is also an evolving subject matter in medicine. There are uncertainties surrounding the pathophysiology of OAB, the strength of a clinical diagnosis, and accurate reporting because of the disease's stigma and decreased use of health care. DATA SOURCES: This is a narrative review that used PubMed, Google Scholar, Medline, and ScienceDirect to review literature on current and future OAB therapies. RESULTS: Currently, first-line treatment for OAB is behavioral therapy that uses lifestyle modifications, bladder-control techniques, and psychotherapy. Second-line therapy includes antimuscarinic agents or beta 3 adrenergic agonists, and studies have shown that combination therapy with antimuscarinics and beta 3 adrenergic agonists provides even greater efficacy than monotherapy. Third-line therapies discussed include onabotulinumtoxinA, posterior tibial nerve stimulation, and sacral neuromodulation. OnabotulinumtoxinA has been FDA-approved as a nonpharmaceutical treatment option for refractory OAB with minimal side effects restricted to the urinary tract. Posterior tibial nerve modulation and sacral neuromodulation are successful in treating refractory OAB, but the costs and complication rates make them high-risk procedures. Therefore, surgical intervention should be a last resort. Estrogen therapy is effective in alleviating urinary incontinence in postmenopausal women, consistent with the association between estrogen deficiency and genitourinary syndrome. Potassium channel activators, voltage-gated calcium channel blockers, and phosphodiesterase inhibitors look to be promising options for the future of OAB management. As new therapies are developed, individuals with OAB can better personalize their treatment to maximize their quality of life and cost-effective care.

Low-Level Laser Therapy for Acute Pain: A Comprehensive Review.

PURPOSE OF REVIEW: An analysis of data conducted in 2015 by the National Health Interview Survey (NHIS) found that an estimated 25.3 million adults (11.2%) have experienced pain every day for the preceding 3 months, and nearly 40 million adults (17.6%) have experienced a severe level of pain. RECENT FINDINGS: Multiple reviews have analyzed the current management of acute pain; however, much of the current literature only focuses on pharmacological methods of analgesia, such as opiates, ketamine, or non-steroidal anti-inflammatory drugs (NSAIDs). Publications that discuss non-pharmacological options often criticize the limitations of available research for these therapies, making further exploration of this type of treatment necessary. The present investigation aims to summarize current knowledge on the use of low-level laser therapy (LLLT), a cold laser non-pharmacological approach, in managing acute pain and to discuss important clinical findings and considerations when it comes to utilizing this treatment option in patients.

Multi-agent Systems and Cancer Pain Management.

PURPOSE: The present investigation explores multi-agent systems, their function in cancer pain management, and how they might enhance patient care. Since cancer is a complex disease, technology can help doctors and patients coordinate care and communicate effectively. Even when a patient has a dedicated team, treatment may be fragmented. Multi-agent systems (MAS) are one component of technology that is making progress for cancer patients. Wireless sensory networks (WSN) and body area sensory networks (BASN) are examples of MAS. RECENT FINDINGS: Technology is advancing the care of patients, not only in everyday clinical practice, but also in creating accessible communication between patients and provider. Many hospitals have utilized electronic medical records (EHR), but recent advancements allowed the pre-existing infrastructure to network with personal devices creating a more congruent form of communications. Better communication can better organize pain management, leading to better clinical outcomes for patients, integrating body sensors, such as smart watch, or using self-reporting apps. Certain software applications are also used to help providers in early detections of some cancers, having accurate results. The integration of technology in the field of cancer management helps create an organized structure for cancer patients trying to understand/manage their complex diagnosis. The systems for the various healthcare entities can receive and access frequently updated information that can better provide better coverage of the patient's pain and still be within the legalities as it pertains to opioid medications. The systems include the EHR communicating with the information provided by the patient's cellular devices and then communicating with the healthcare team to determine the next step in management. This all happens automatically with much physical input from the patient decreasing the amount of effort from the patient and hopefully decreasing the number of patients' loss to follow-up.

The Emerging Role of Ketamine in Acute Postoperative Pain Management.

PURPOSE OF REVIEW: Postoperative pain (POP) is among the most unpleasant experiences that patients face after surgery. Interest in and use of N-methyl-D-aspartate (NMDA) receptor antagonists for the management of POP has increased over the years with ketamine being the most popular drug of this class. RECENT FINDINGS: Several randomized controlled trials found that the use of ketamine either alone or in combination with other medications leads to decreased postoperative pain and opioid consumption. However, there are other studies that have not found these benefits. The results as of now suggest that the role of intraoperative ketamine in postoperative pain control varies among different operative procedures. While some studies have shown promise in ketamine's potential use as a postoperative analgesic, there is still a great deal of proposed research and randomized controlled trials needed to deduce the most efficacious and tolerable form and dose of ketamine.

Cebranopadol for the Treatment of Chronic Pain.

PURPOSE OF REVIEW: Regardless of the etiology, if pain persists chronically, it can detrimentally impact multiple aspects of a patient's well-being. Both physical and psychological effects are significant in many chronic pain patients. In this regard, psychological consequences can alter a patient's quality of life, functionality, and social functioning. Opioids have been the long-established gold standard for acute pain treatment in settings such as the postoperative period. An alternative to opioids in pain management has been highly sought after. Through a non-selective mechanism, cebranopadol is a first-in-class oral drug which combines agonism of the mu and nociceptin opioid peptide (NOP) receptors to provide improved analgesia, while reducing the occurrence of many typically opioid side effects. This manuscript is a narrative review of the possible use of cebranopadol in pain management. RECENT FINDINGS: In pre-clinical studies, cebranopadol was similar to morphine in its pain control efficacy. In a phase IIa trial, cebranopadol was superior to placebo in reducing pain. In a randomized clinical trial, cebranopadol was superior to morphine. Another study concluded that cebranopadol had a lower misuse potential when compared to hydromorphone. In summary, cebranopadol offers new opportunities in treating chronic moderate to severe pain, while also countering risks of addiction. Additional studies are warranted to further evaluate the safety and efficacy of cebranopadol. In this regard, cebranopadol could prove to be a promising alternative to current pain treatment options.

Treatment of Acute Pain in Patients on Naltrexone: A Narrative Review.

PURPOSE OF REVIEW: The tissue damage and trauma associated with surgery almost always result in acute postoperative pain. The intensity of postoperative pain can range from mild to severe. Naltrexone is suitable for patients who do not wish to be on an agonist treatment such as methadone or buprenorphine. However, naltrexone has been shown to complicate postoperative pain management. RECENT FINDINGS: Multiple studies have found that the use of naltrexone can increase the opioid requirement for postoperative pain control. Other modalities exist that can help outside of opioids such as ketamine, lidocaine/bupivacaine, duloxetine, and non-pharmacological management can help manage pain. Multimodal pain regiments should also be employed in patients. In addition to traditional methods for postoperative pain management, other methods of acute pain control exist that can help mitigate opioid dependence and help control pain in patients who use naltrexone for their substance use disorders.

Algorithms to Identify Nonmedical Opioid Use.

The rise in nonmedical opioid overdoses over the last two decades necessitates improved detection technologies. Manual opioid screening exams can exhibit excellent sensitivity for identifying the risk of opioid misuse but can be time-consuming. Algorithms can help doctors identify at-risk people. In the past, electronic health record (EHR)-based neural networks outperformed Drug Abuse Manual Screenings in sparse studies; however, recent data shows that it may perform as well or less than manual screenings. Herein, a discussion of several different manual screenings and recommendations is contained, along with suggestions for practice. A multi-algorithm approach using EHR yielded strong predictive values of opioid use disorder (OUD) over a large sample size. A POR (Proove Opiate Risk) algorithm provided a high sensitivity for categorizing the risk of opioid abuse within a small sample size. All established screening methods and algorithms reflected high sensitivity and positive predictive values. Neural networks based on EHR also showed significant effectiveness when corroborated with Drug Abuse Manual Screenings. This review highlights the potential of algorithms for reducing provider costs and improving the quality of care by identifying nonmedical opioid use (NMOU) and OUD. These tools can be combined with traditional clinical interviewing, and neural networks can be further refined while expanding EHR.

The Use of Oxytocin for the Treatment of Opioid Use Disorder.

Nearly 27 million people have an opioid use disorder (OUD) according to the 2016 Global Burden of Disease study, most of which occur in the US where opioids are a common class of medication used to treat acute and chronic pain. In 2016 alone, more than 60 million patients had at least one prescription for opioids filled or refilled. Over the past decade, prescription rates have risen astronomically and have created an epidemic in the US dubbed the "opioid crisis." In this regard, there has been an increase in overdoses and OUD diagnoses. Several studies have found dysregulation of balance between several neurotransmitters involved in the neural circuitry that subserves several behavioral domains, such as reward recognition, motivation, learning, and memory, affect, stress, and executive function, that contribute to the manifestation of craving. On the horizon is a new treatment approach consisting of the neuropeptide oxytocin, which may be involved in the overlapping mechanisms of stable attachment formation and coping with stress. Through this mechanism, it can shift processing from novelty and reward-seeking to an appreciation of familiarity and thus reduce stress and increase resilience in the face of addiction. It has been hypothesized that there is a connection between the glutaminergic and oxytocinergic systems, making oxytocin a possible therapeutic agent in reducing drug-induced actions seen in OUD patients. This manuscript will review the potential and feasible use of oxytocin in treating OUD.

Low-Dose Initiation of Buprenorphine: A Narrative Review.

PURPOSE OF REVIEW: Opioid use disorder (OUD) is a chronic disorder in which a person loses control over the use of opioids, develops a compulsive behavior, and defends the use despite knowing the negative consequences. There are numerous treatments for OUD, including buprenorphine. Since it is displacing a full agonist opioid, precipitated withdrawal can occur with standard inductions involving buprenorphine. RECENT FINDINGS: Case reports have noted success with a low-dose initiation of buprenorphine, which is different from typical protocols, relatively limited by adverse effects when patients were recently administered full agonists. A cohort investigation studied the use of a transdermal patch as part of the protocol, which was fairly well tolerated. While ongoing research is being conducted on this topic, recent case studies and smaller cohort studies have demonstrated the feasibility of a trial to treat OUD with low-dose initiation of buprenorphine.

Electronic Health Record Recording of Patient Pain: Challenges and Discrepancies.

PURPOSE OF REVIEW: In the present review, various categories of pain, clinician-observed pain scales, and patient-reported pain scales are evaluated to better understand factors that impact patient pain perceptions. Additionally, the expansion of areas that require further research to determine the optimal way to evaluate pain scale data for treatment and management are discussed. RECENT FINDINGS: Electronic health record (EHR) data provides a starting point for evaluating whether patient predictors influence postoperative pain. There are several ways to assess pain and choosing the most effective form of pain treatment. Identifying individuals at high risk for severe postoperative pain enables more effective pain treatment. However, there are discrepancies in patient pain reporting dependent on instruments used to measure pain and their storage in the EHR. Additionally, whether administered by a physician or another healthcare practitioner, differences in patient pain perception occur. While each scale has distinct advantages and limitations, pain scale data is a valuable therapeutic tool for assisting clinicians in providing patients with optimal pain control. Accurate assessment of patient pain perceptions by data extraction from electronic health records provides a potential for pain alleviation improvement. Predicting high-risk postoperative pain syndromes is a difficult clinical challenge. Numerous studies have been conducted on factors that impact pain prediction. Postoperative pain is significantly predicted by the kind of operation, the existence of prior discomfort, patient anxiety, and age.

Platelet-Rich Plasma Injections: Pharmacological and Clinical Considerations in Pain Management.

PURPOSE OF REVIEW: Regenerative medicine through interventional pain procedures is evolving with data demonstrating efficacy for a number of pain states in recent years. Platelet-rich plasma (PRP), defined as a sample of plasma with a platelet concentration 3 to 5 times greater than the physiologic platelet concentration found in healthy whole blood, releases bioactive proteins which can restore anatomical function in degenerative states. PRP is dense in growth factors, such as platelet-derived growth factor, transforming growth factor-beta1, basic fibroblastic growth factor, vascular endothelial growth factor, and epidermal growth factors. RECENT FINDINGS: To date, well-designed case-control or cohort studies for the use of PRP have demonstrated efficacy in lumbar facet joint, lumbar epidural, and sacroiliac joint injections. At present, there is only level IV evidence indicating the need for larger and more carefully controlled prospective studies. PRP is utilized autogenously in order to facilitate healing and injection and has been studied in the long-term management of discogenic low back pain. In this regard, numerous studies have evaluated PRP to steroid injections in chronic pain states with favorable results. PRP represents an opportunity for a new strategy in the therapeutic treatment of degenerative states of spines, joints, and other locations throughout the body with evolving data demonstrating both safety and long-term efficacy.

Regenerative Medicine: Pharmacological Considerations and Clinical Role in Pain Management.

PURPOSE OF REVIEW: Low back pain affects at least 80% of individuals at some point in their lifetime and is the fifth most common reason for physician visits in the USA. Treatment of an acute episode of LBP generally includes rest, activity modification, physical therapy, NSAIDs, and patient education. RECENT FINDINGS: A small percentage of patients will develop chronic pain lasting > 6 months duration. Platelet-rich plasma (PRP) is one of the main pillars of regenerative medicine, as its release of bioactive proteins supports the aim of RM of restoring the anatomical function in degenerative conditions. Mesenchymal stem cells (MSCs) are multipotent stem cells, multipotent progenitor cells, or marrow stromal cells found in various body tissues, including bone marrow, lung, and adipose tissue. Evidence from well-designed case-control or cohort studies for the use of PRP and MSCs in lumbar facet joint, lumbar epidural, and sacroiliac joint injections is currently described as level IV evidence. PRP and MSCs are used autogenously to help facilitate the healing process, and their injection has been studied in the long-term management of discogenic low back pain. PRP has been compared to steroid injections in the sacroiliac joint for chronic low back pain, with favorable results. MSCs have also been shown to be useful in intervertebral disc regeneration and treatment of chronic low back pain associated with degenerative disc disease. Currently, the price for these treatments is extremely high, and thus the standard of care continues to be steroid injections and other treatments. This could change, however, with more robust data and research on the safety and long-term efficacy of biologics compared to other interventional management.

Treatment and Management of Loin Pain Hematuria Syndrome.

PURPOSE OF REVIEW: Loin pain hematuria syndrome (LPHS) is rare and seldom diagnosed, yet it has a particularly significant impact on those affected. This is a review of the latest and seminal evidence of the pathophysiology and diagnosis of LPHS and presents the typical clinical presentation and treatment options available. RECENT FINDINGS: LPHS is typically found in young women with characteristic symptoms, including severe recurrent flank pain and gross or microscopic hematuria. The majority of patients will experience crippling pain for many years without effective therapy, often requiring frequent use of narcotic medication. However, the lack of conclusive pathophysiology, in conjunction with the rarity of LPHS, has prohibited the development and trial of definitive treatment options. Nevertheless, in order to combat this rare but severe disease, management strategies have continued to evolve, ranging from conservative measures to invasive procedures. This review presents an overview of the current hypotheses on the pathophysiology of LPHS in addition to summarizing the management strategies that have been utilized. Only 30% of LPHS patients will experience spontaneous resolution, whereas the majority will continue to face chronic, crippling pain. Several methods of treatment, including invasive and non-invasive, may provide an improved outcome to these patients. Treatment should be individually tailored and multi-disciplinary in nature. Further research is required to further elucidate the pathophysiology and develop new, specific, treatment options.

Moderate and deep procedural sedation-the role of proper monitoring and safe techniques in clinical practice.

PURPOSE OF REVIEW: Interventional pain management procedures provide significant improvement to patient quality of life and functionality. In-office procedures are becoming an increasingly more common site of pain management intervention for patients with minimal risk of harm. RECENT FINDINGS: Moderate and deep sedation techniques can be used in patients with high anxiety, complex pharmacotherapy, or a low pain threshold. Proper guidance and oversight by an attending anesthesiologist, in addition to appropriate monitoring, are key. Epidural steroid injection complications rates have been cited at 2.4%, with the most common complications noted as persistent pain and flushing. SUMMARY: Serious complication errors can be avoided with proper supervision and monitoring. The adherence to published societal recommendations and guidelines for indications of when to use moderate to deep sedation techniques, and appropriate supervision and monitoring methods, can avoid errors in interventional pain management procedures.

Pharmacogenomics of Pain Management: The Impact of Specific Biological Polymorphisms on Drugs and Metabolism.

PURPOSE OF REVIEW: Pain is multifactorial and complex, often with a genetic component. Pharmacogenomics is a relative new field, which allows for the development of a truly unique and personalized therapeutic approach in the treatment of pain. RECENT FINDINGS: Until recently, drug mechanisms in humans were determined by testing that drug in a population and calculating response averages. However, some patients will inevitably fall outside of those averages, and it is nearly impossible to predict who those outliers might be. Pharmacogenetics considers a patient's unique genetic information and allows for anticipation of that individual's response to medication. Pharmacogenomic testing is steadily making progress in the management of pain by being able to identify individual differences in the perception of pain and susceptibility and sensitivity to drugs based on genetic markers. This has a huge potential to increase efficacy and reduce the incidence of iatrogenic drug dependence and addiction. The streamlining of relevant polymorphisms of genes encoding receptors, transporters, and drug-metabolizing enzymes influencing the pain phenotype can be an important guide to develop safe new strategies and approaches to personalized pain management. Additionally, some challenges still prevail and preclude adoption of pharmacogenomic testing universally. These include lack of knowledge about pharmacogenomic testing, inadequate standardization of the process of data handling, questionable benefits about the clinical and financial aspects of pharmacogenomic testing-guided therapy, discrepancies in clinical evidence supporting these tests, and doubtful reimbursement of the tests by health insurance agencies.

The Impact of the Quantity and Quality of Social Support on Patients with Chronic Pain.

PURPOSE OF REVIEW: Social support is an important yet often overlooked aspect of chronic pain management. Understanding the impact of social support on patients with chronic pain and determining if a relationship exists between a patient's perceived social support and their perceived quality of life is a crucial component to completely treating a pain patient. We sought to develop an intervention for patients with chronic pain that addresses the different types of social support, barriers to using social support, and ways to improve the quality of their social support. RECENT FINDINGS: A retrospective review of a prospectively collected database was utilized in an Outpatient Chronic Pain Rehabilitation Program with 23 patients with a chronic pain diagnosis who participated in a 3-week comprehensive pain rehabilitation program. Evaluation, intervention, and discharge were evaluated utilizing The American Chronic Pain Association's Quality of Life Scale and The Canadian Occupational Performance Measure (COPM). The intervention phase comprised a 45-min group session. At discharge, the occupational therapist followed up with the patient regarding the results of their social survey. Overall, the results indicated an underutilization of social support among patients with chronic pain. Out of the four questions asked on the social support survey, patients scored their use of tangible support (Q2) as the lowest. No significant positive correlation (0.27) was found between social support and quality of life which can be attributed to the wide variety of patients seen at the PRC. Social support is an essential part of chronic pain treatment and should be addressed throughout all stages of pain management.

Novel Agents in Neuropathic Pain, the Role of Capsaicin: Pharmacology, Efficacy, Side Effects, Different Preparations.

PURPOSE OF REVIEW: Capsaicin is a natural substance used to treat neuropathic pain because of its ability to be used in a more direct form on patients and efficiently treat their pain without the amount of side effects seen in the use of oral medications. RECENT FINDINGS: Currently, the treatments for neuropathic pain are, control of the underlying disease process, then focused on symptomatic relief with pharmacotherapy, topical analgesics, or other interventions. When all pharmacological agents fail to relieve the pain, interventional strategies can be considered, such as neural blocks, spinal cord stimulation, and intrathecal administered medications. The response to current treatment of neuropathic pain is only modest relief of symptoms. Multiple treatment options may be attempted, while ultimately leaving patients with refractory neuropathic pain. For these reasons, a better treatment approach to neuropathic pain is greatly needed. Overall, capsaicin has great potential for becoming a first- or second-line treatment for neuropathic pain, and for becoming a therapeutic option for many other neuropathic pain-related disease states.

Exparel for Postoperative Pain Management: a Comprehensive Review.

PURPOSE OF REVIEW: Multimodal pain management is the most effective way to treat postsurgical pain. However, the use of opioids for acute pain management has unfortunately been a significant contributor to the current opioid epidemic. The use of opioids should be limited and only considered a "rescue" pain medication after other modalities of pain management have been utilized. RECENT FINDINGS: It may be difficult to curtail the use of opioids in the treatment of chronic pain; however, in the postsurgical setting, there is compelling evidence that an opioid-centric analgesic approach is not necessary for good patient outcomes and healthcare cost benefits. Opioid-related adverse effects are the leading cause of preventable harm in the hospital setting. After the realization in recent years of the many harmful effects of opioids, alternative regimens including the use of multimodal analgesia have become a standard practice in acute pain management. Exparel, a long-lasting liposomal bupivacaine local anesthetic agent, has many significant benefits in the management of postoperative pain. Overall, the literature suggests that Exparel may be a significant component for postoperative multimodal pain control owing to its efficacy and long duration of action.

A Comprehensive Review of the Diagnosis, Treatment, and Management of Urologic Chronic Pelvic Pain Syndrome.

PURPOSE OF REVIEW: Urologic chronic pelvic pain syndrome (UCPPS) is a chronic, noncyclic pain condition which can lead to significant patient morbidity and disability. It is defined by pain in the pelvic region, lasting for greater than 3 to 6 months, with no readily identifiable disease process. The aim of this review is to provide a comprehensive update of diagnosis and treatment of UCPPS. RECENT FINDINGS: UCPPS encompasses chronic pelvic pain syndrome or chronic prostatitis (CP/CPPS) in men and interstitial cystitis or painful bladder syndrome (IC/PBS) in women. Underlying inflammatory, immunologic, and neuropathic components have been implicated in the pathogenesis of UCPPS. For optimal patient management, an individualized and multimodal approach is recommended. Medical management and physical therapy are the mainstays of treatment. Injection therapy may offer additional relief in medically refractory patients. Further minimally invasive management may include spinal cord and peripheral nerve stimulation, though evidence supporting efficacy is limited.

Dexmedetomidine in Enhanced Recovery After Surgery (ERAS) Protocols for Postoperative Pain.

PURPOSE OF REVIEW: Effective acute pain management has evolved considerably in recent years and is a primary area of focus in attempts to defend against the opioid epidemic. Persistent postsurgical pain (PPP) has an incidence of up to 30-50% and has negative outcome of quality of life and negative burden on individuals, family, and society. The 2016 American Society of Anesthesiologists (ASA) guidelines states that enhanced recovery after surgery (ERAS) forms an integral part of Perioperative Surgical Home (PSH) and is now recommended to use a multimodal opioid-sparing approach for management of postoperative pain. As such, dexmedetomidine is now being used as part of ERAS protocols along with regional nerve blocks and other medications, to create a satisfactory postoperative outcome with reduced opioid consumption in the Post anesthesia care unit (PACU). RECENT FINDINGS: Dexmedetomidine, a selective alpha2 agonist, possesses analgesic effects and has a different mechanism of action when compared with opioids. When dexmedetomidine is initiated at the end of a procedure, it has a better hemodynamic stability and pain response than ropivacaine. Dexmedetomidine can be used as an adjuvant in epidurals with local anesthetic sparing effects. Its use during nerve blocks results in reduced postoperative pain. Also, local infiltration of IV dexmedetomidine is associated with earlier discharge from PACU. Perioperative use of dexmedetomidine has significantly improved postoperative outcomes when used as part of ERAS protocols. An in-depth review of the use of dexmedetomidine in ERAS protocols is presented for clinical anesthesiologists.