Pain Management Therapy Research Articles

Wood and Coal Burning Stoves as a Risk Factor for Falls in Rural, Geriatric Patients: A Case Series

In rural communities, geriatric patients often rely on wood or coal stoves for heat and food preparation. These stoves present serious fall risks: besides fume inhalation and exposure to benzene, carbon monoxide, and polycyclic aromatic hydrocarbons, the physical act of loading a stove can present a serious biomechanical challenge to frail patients. Moreover, since rural housing is often isolated, patients who suffer falls in these contexts can remain immobilized on the ground for hours or even days. In this brief report, we present two geriatric cases in which coal-burning stoves likely played a causal role in a patient's fall and complicated post-rehab discharge planning. Both cases involve frail, elderly females with significant comorbidities found on the floor in farmhouses that smelled of fumes from coal-burning stoves who suffered physiological consequences related to their particular anatomical risk factors. One patient required ICU treatment for severe rhabdomyolysis, while the other suffered an acute compression fracture that required prolonged pain management and intensive physical therapy. Despite the sparseness of the literature on coal or wood stoves as a risk factor for geriatric falls, these cases highlight the value of asking specifically about these stoves in fall risk assessment and discharge planning for rural, geriatric patients.

Association between marijuana use and nonmedical prescription opioid use in the United States: are we shifting from one epidemic to another?

The United States (US) is grappling with a severe opioid epidemic. Marijuana is emerging as a therapy for pain management and an alternative to opioids, but little evidence supports its long-term benefits.This study aims to examine the association of marijuana use among patients on prescription pain relievers in a retrospective cross-sectional study using zero-inflated negative binomial regression. The recipients of prescription pain medicines were identified using National Survey on Drug Use and Health (2015-2017). Irrespective of the state marijuana laws, marijuana use days were 34% higher and odds of having zero days of marijuana use were 73% lower in those using nonmedical prescription opioids vs. not (IRR = 1.34, p < 0.0001; OR = 0.27, p < 0.0001, respectively). In the absence of consequential evidence supporting marijuana for pain management and more states venturing into legalizing it, there needs to be more caution as the country struggles to recover from one epidemic.

Perceptions of nonopioid treatment for pain in a homeless population.

Opioid abuse has developed into a public health emergency within the last decade because opioid medications, while addictive, are effective and commonly used for pain management. In 2016, over 42,000 deaths were attributed to opioids. Chronic pain affects about 50% of people experiencing homelessness in the US, and they have a higher overall rate of chronic pain than the general population; opioids are among the methods they might use to manage that pain. Complementary and alternative therapies for pain management have largely gone unexplored in the homeless population. To determine, among people experiencing homelessness, the willingness to use and current use of complementary and alternative treatments (physical and massage therapy, chiropractic treatments). A secondary objective was to investigate awareness and perception of osteopathic manipulative treatment (OMT) as a complementary treatment for chronic pain among the homeless population. A 32 question survey was administered verbally to guests of True Worth Place Homeless Shelter in Fort Worth, Texas in three 4hour sessions from February 2019 to April 2019. If participants gave verbal consent, a researcher read the questionnaire, one question at a time, and recorded the participant's responses. The survey included queries for opioid and nonopioid treatment modalities (physical and massage therapy, chiropractic, and OMT) to assess the perception of and current use of each among the population. Appropriate nonparametric statistical analysis was conducted to assess significance and correlations among the treatment groups. Of the 200 survey participants, 126 (91.3%) reported a history of opiate use for pain, but 136 (68.0%) believed that a nondrug pain intervention could better treat their pain. Additionally, 150 participants (75.0%) believed that regular manipulation, including OMT, would decrease their need for pain medications. Participants with a history of opioid use for pain were more likely to believe that the availability of regular manipulation, including OMT, at True Worth Place could decrease their need for pain medication (odds ratio=3.7143; 95% confidence interval=1.6122-8.5572; p=0.0009). Moreover, some participants (141; 70.5%) were already pursuing nondrug pain management modalities such as PT, massage therapy, and chiropractic care. The greatest barriers to receiving OMT were transportation and cost. This survey study was conducted to determine whether a homeless population would be willing to use nonopioid treatment, particularly OMT, for chronic pain management. Results revealed both a willingness to use and a previous use of nonopioid treatments for pain, along with a high prevalence of opiate use. Despite limited exposure to OMT, this population reported being potentially willing to pursue manipulation, including OMT, as a complementary treatment for pain relief alongside opioids if readily available.

AXILLARY NERVE SUPPLYING MOTOR BRANCH TO LONG HEAD OF TRICEPS BRACHII MUSCLE: A CASE REPORT AND REVIEW OF LITERATURE

All three heads of the triceps brachii are classically described as being innervated by the radial nerve in the textbooks. Some clinical observations of traumatic injuries of the axillary nerve with associated paralysis of the long head of triceps and cadaveric studies have suggested that the axillary nerve may innervate the long head of triceps. During routine dissection to undergraduate M.B.B.S students, we found axillary nerve giving a motor branch to long head of triceps brachii on right side, in an adult male cadaver aged about 60 years. We conducted extensive literature search to analyse the previous studies reporting such variations and the studies conducted on the radial nerve or triceps brachii innervation pattern. This variation is clinically important for surgeons, orthopedicians and anaesthetist while performing surgeries and pain management therapies on the upper limb.

Biologic Therapy in Chronic Pain Management: a Review of the Clinical Data and Future Investigations.

With the aging population, it is clear that the demand for future chronic pain treatment modalities is at an all-time high. One of the newest treatment modalities that is gaining popularity with both practitioners and patients alike is that of regenerative medicine and the use of stem cells to treat chronic painful conditions. This article aims to distill the most recent, available data from both laboratory research and clinical trials to better illuminate the potentials for these therapies in the treatment of chronic pain. There are numerous investigations underway using mesenchymal stem cells (MSCs) to treat painful, largely degenerative conditions. A large majority of these investigations focus on osteoarthritis of the knee and have demonstrated significantly improved pain scores. Some of these investigations have demonstrated significantly increased articular cartilage and meniscus growth as well as improved function. These studies have been smaller (n, 18) and need to be corroborated on a macrolevel. Platelet-rich plasma (PRP)-based therapies have been most extensively studied in the treatment of knee osteoarthritis. Multiple prospective and randomized trials and meta-analyses have afforded level I evidence in support of PRP's safety and efficacy in chronic knee pain demonstrating both decreased pain (via VAS) and increased functional status (via WOMAC and IKDC). There have been randomized controlled trials examining PRP therapies in treatment degenerative disc disease (intradiscal treatment), facet arthropathy (intra-facet injections), and sacroiliitis (SIJ) which have all yielded similar positive results. Each RTC demonstrated decreased pain scores and increased function but lacks the scale to derive concrete guidelines. Newer investigations are underway examining modified PRP formulas with increased fibrin (PRF) or various growth factors (PRGF) and have shown positive outcomes with respect to osteoarthritic conditions in small trials. Animal trials are underway further investigating these therapies as well as specific gene modulation therapies. This review of the most recent investigations into the application and uses of biologic stem cell-derived treatments for chronic painful conditions should act to illustrate the growing, favorable data for these types of modalities both with respect to pain control and functional improvement.

Participation in an Advanced Anatomy Capstone Project Facilitates Student Involvement in the Development of an Instructional Tool for Novel Dissection

Introduction. Student-driven design of instructional tools within basic sciences curricula in general, and in anatomy in particular, has been shown to be both a positive educational experience for the student developers and a viable way to create quality materials for future courses. We present here a description of a student collaboration arising from participation in an advanced anatomy capstone research project, resulting in the creation of a new dissection protocol for the thoracolumbar junction dorsal primary rami and their branches. Materials and Methods. This project was initiated by two third-year doctor of physical therapy (DPT) students and involved participation from faculty and other DPT students of varying experience levels, in order to pilot and refine the tool over a two-year period. We describe the process by which the tool was developed, from the genesis of the original idea through the piloting stage. Results and Discussion. This collaboration resulted in a new instructional tool to be launched within our first-year DPT gross anatomy labs in 2022. Evaluation of the project through qualitative interviews demonstrated the learning impact on student participants. Conclusions. The success of this project shows the potential for students to be meaningfully involved in instructional tool design. The complete dissection guide, along with photos, is included and will be of particular relevance for medical and health science educators with an interest in orthopedics, neurosurgery, pain management, or physical therapy.

Intrathecal Drug Therapy in Chronic Pain Management

Chronic pain impacts the quality of multiple functional domains, including family life, workplace performance, social interactions, and sleep patterns. The management of chronic pain continues to pose many challenges to healthcare providers. Intrathecal drug delivery systems (IDDS) provide an effective therapy for patients suffering from chronic pain intractable to medical management. to identify best practices and provide guidance to clinicians to ensure safety and optimize intrathecal drug delivery for chronic intractable pain management. This is a review article, The search was performed in MEDLINE, Embase, Pubmed and CINAHL Plus in the same date range with the following mediacl terms. Intrathecal drug (IT) delivery has many benefits compared with oral or parenteral routes for pain control. First, it allows for the use of significantly lesser doses of opioids. Second, it bypasses the first pass effect and the blood brain barrier. Third, patients typically experience fewer adverse effects (AEs) due to the decreased total dose of opioid used. However, IT therapy may be associated with complications related to many factors, including those related to the IT pump itself (e.g., mechanical failure), pump pocket fills, issues surrounding preparation of the IT medication and programming of the pump for medication release, and complications following pump implantation surgery. Optimal use of this therapy depends on a thorough understanding of intrathecal physiology and anatomy as well appreciation of physicochemical properties of administered medications and the mode of IT delivery.

Increasing Access to Interventional Pain Management Therapies for Palliative Care Patients with Cancer Through Referral System Improvement (F425D)

Increasing Access to Interventional Pain Management Therapies for Palliative Care Patients with Cancer Through Referral System Improvement (F425D)

Pharmacokinetic neuroimaging to study the dose-related brain kinetics and target engagement of buprenorphine in vivo.

A wide range of buprenorphine doses are used for either pain management or maintenance therapy in opioid addiction. The complex in vitro profile of buprenorphine, with affinity for µ-, δ-, and κ-opioid receptors (OR), makes it difficult to predict its dose-related neuropharmacology in vivo. In rats, microPET imaging and pretreatment by OR antagonists were performed to assess the binding of radiolabeled buprenorphine (microdose 11C-buprenorphine) to OR subtypes in vivo (n = 4 per condition). The µ-selective antagonist naloxonazine (10 mg/kg) and the non-selective OR antagonist naloxone (1 mg/kg) blocked the binding of 11C-buprenorphine, while pretreatment by the δ-selective (naltrindole, 3 mg/kg) or the κ-selective antagonist (norbinaltorphimine, 10 mg/kg) did not. In four macaques, PET imaging and kinetic modeling enabled description of the regional brain kinetics of 11C-buprenorphine, co-injected with increasing doses of unlabeled buprenorphine. No saturation of the brain penetration of buprenorphine was observed for doses up to 0.11 mg/kg. Regional differences in buprenorphine-associated receptor occupancy were observed. Analgesic doses of buprenorphine (0.003 and 0.006 mg/kg), respectively, occupied 20% and 49% of receptors in the thalamus while saturating the low but significant binding observed in cerebellum and occipital cortex. Occupancy >90% was achieved in most brain regions with plasma concentrations >7 µg/L. PET data obtained after co-injection of an analgesic dose of buprenorphine (0.003 mg/kg) predicted the binding potential of microdose 11C-buprenorphine. This strategy could be further combined with pharmacodynamic exploration or pharmacological MRI to investigate the neuropharmacokinetics and neuroreceptor correlate, at least at µ-OR, of the acute effects of buprenorphine in humans.

Anti-nociceptive and Anti-inflammatory Activity of Synthesized Novel Benzoxazole Derivatives.

Pain is an immunological response to an infection or inflammation and long-term use of pain management therapy includes the use of Nonsteroidal anti-inflammatory drugs, which is associated with the occurrence of toxicity as well as gastrointestinal bleeding. Therefore, the investigation of new analgesic and anti-inflammatory agents remains a major challenge. The objective of this research study is to undergo the pharmacological evaluation of newly synthesized benzoxazole derivatives. These novel derivatives were evaluated for anti-nociceptive, anti-inflammatory and cytotoxic activity using various in-vivo and ex-vivo methods Methods: The study was carried out using swiss mice (adult male) weighing between 20gm to 30gm and were divided into groups containing (n=6) six animals in each group for treatment. The anti-nociceptive activity was performed by using 0.1ml of 0.6% v/v acetic acid as nociception inducer and evaluated by the diminished number of abdominal writhes. The anti-inflammatory activity was done using 0.1 ml of 2% w/v Carrageenan induced paw edema method was observed which was evaluated by calculating the percent maximum possible effect. Histopathological evaluation and cytotoxic activity of the compounds were carried out. The results of this research study revealed that synthesized derivatives (a, b, c, d and e) showed promising anti-nociceptive and anti-inflammatory effects along significantly higher cytotoxic activity in MCF-7 cell lines. It can be concluded that synthesized derivatives (a, b, c, d and e) have potential anti- nociceptive and anti-inflammatory effects along with cytotoxic activity and certain modification in structure may result in the potent activity.

Effectiveness of Mobilizations along With Hot Therapy versus Mobilizations for Management of Chronic Neck Pain Due to Over Usage of Smart Phones among Young at LUMHS Jamshoro

Objective: To determine the effectiveness of mobilizations along with hot therapy versus mobilizations for the management of chronic neck pain due to over usage of smart phones among young.&#x0D; Materials and Methods: This interventional clinical trial was conducted at OPD, Institute of Physiotherapy &amp; Rehabilitation Sciences (IPRS) in Liaquat University Medical and Health Sciences Jamshoro (LUMHS). All the individuals from LUMHS Jamshoro including students, age 18-35 years and either of gender were included. All the individuals were divided in two groups (group A and group B). Cases of group A were underwent management of mobilization with hot therapy and cases of group B underwent only mobilization management. Outcome was observed in the terms of decrease the pain during work, reading and sleeping. All the data was recorded via study proforma.&#x0D; Results: Total 64 individuals were studied. Mean age was 26.2+4.2 years in group A and 28.6+5.3years. Males were in majority in both groups. According to the pain assessment on movement, mild pain was in 18.8%, moderate pain was 50.0%, severe pain was in 12.5% and very severe pain was in 18.85 of the patients of group A. However in group B most of the patients 93.8% had mild pain and 6.2% patients had severe pain, while no any patients with moderate pain and very severe pain was found in group B. After treatment pain was more decreased in patients of group A as pain during work, reading and sleeping was significantly higher in only mobilizations treatment group as compared to those underwent mobilizations with hot therapy treatment, p-values were quite significant.&#x0D; Conclusion: It was concluded that the treatment of mobilization with Hot pack was more effective than treatment only mobilization.

Obstetric Physicians' Beliefs and Knowledge on Guidelines and Screening Tools to Reduce Opioid Use After Childbirth.

To examine obstetric physicians' beliefs about using professional or regulatory guidelines, opioid risk-screening tools, and preferences for recommending nonanalgesic therapies for postpartum pain management. A qualitative study design was used to conduct semi-structured interviews with obstetric and maternal-fetal medicine physicians (N=38) from two large academic health care institutions in central Pennsylvania. An interview guide was used to direct the discussion about each physicians' beliefs in response to questions about pain management after childbirth. Three trends in the data emerged from physicians' responses: 1) 71% of physicians relied on their clinical insight rather than professional or regulatory guidelines to inform decisions about pain management after childbirth; 2) although many reported that a standard opioid patient screening tool would be useful to inform clinical decisions about pain management, nearly all (92%) physician respondents reported not currently using one; and 3) 63% thought that nonpharmacologic pain management therapies should be used whenever possible to manage pain after childbirth. Key physician barriers (eg, lack time and evidence, being unaware of how to implement) and patient barriers (eg, take away from other responsibilities, no time or patience) to implementation were also identified. These findings suggest that obstetric physicians' individual beliefs and clinical insight play a key role in pain management decisions for women after childbirth. Practical and scalable strategies are needed to: 1) encourage obstetric physicians to use professional or regulatory guidelines and standard opioid risk-screening tools to inform clinical decisions about pain management after childbirth, and 2) educate physicians and patients about nonopioid and nonpharmacologic pain management options to reduce exposure to prescription opioids after childbirth.

Effect of transcutaneous electrical nerve stimulation on quality of recovery and pain after abdominal hysterectomy.

Background and Aims:Transcutaneous electrical nerve stimulation (TENS) is a noninvasive complementary therapy for postoperative pain management. The effect of TENS on quality of recovery (QoR) and pain treatment in the early postoperative period is not well documented. The aim of this study was to evaluate the effect of TENS on postoperative QoR and pain in patients who had undergone a total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH + BSO).Material and Methods:Fifty-two patients were randomized into two groups: control (sham TENS treatment) and TENS (TENS treatment). QoR, dynamic pain, and static pain were evaluated after surgery.Results:The QoR score was significantly higher in the TENS group as compared with that in the control group (P = 0.029). Pain scores during coughing (dynamic pain) were significantly less in TENS group compared to control group (P <0.001). However, there was no between-group difference in pain scores at rest (static pain) or total analgesic consumption (P = 0.63 or P = 0.83, respectively).Conclusion:TENS may be a valuable tool to improve patients' QoR and dynamic pain scores after TAH + BSO.

Rural Emergency Medical Service Providers Perceptions on the Causes of and Solutions to the Opioid Crisis: A Qualitative Assessment.

Introduction:The continuing opioid crisis poses unique challenges to remote and often under-resourced rural communities. Emergency medical service (EMS) providers serve a critical role in responding to opioid overdose for individuals living in rural or remote areas who experience opioid overdoses. They are often first at the scene of an overdose and are sometimes the only health care provider in contact with an overdose patient who either did not survive or refused additional care. As such, EMS providers have valuable perspectives to share on the causes and consequences of the opioid crisis in rural communities.Methods:EMS providers attending a statewide EMS conference serving those from greater Minnesota and surrounding states were invited to take a 2-question survey asking them to reflect upon what they believed to be the causes of the opioid crisis and what they saw as the solutions to the opioid crisis. Results were coded and categorized using a Consensual Qualitative Research approach.Results:EMS providers’ perceptions on causes of the opioid crisis were categorized into 5 main domains: overprescribing, ease of access, socioeconomic vulnerability, mental health concerns, and lack of resources and education. Responses focused on solutions to address the opioid crisis were categorized into 5 main domains: need for increased education, enhanced opioid oversight, increased access to treatment programs, alternative therapies for pain management, and addressing socioeconomic vulnerabilities.Conclusion:Along with the recognition that the opioid crisis was at least partially caused by overprescribing, rural EMS providers who participated in this study recognized the critical role of social determinants of health in perpetuating opioid-related harm. Participants in this study reported that education and increased access to treatment facilities and appropriate pain management, along with recognition of the role of social determinants of health in opioid dependency, were necessary steps to address the opioid crisis.

Does Marijuana Legalization Affect Work Capacity? Evidence from Workers’ Compensation Benefits

We study the effect of state recreational marijuana laws (RMLs) on workers’ compensation (WC) benefit receipt among adults 40-62 years. We find that WC receipt declines in response to RML adoption both in terms of the propensity to receive benefits and benefit amount. We estimate complementary declines in non-traumatic workplace injury rates and the incidence of work-limiting disabilities. We offer evidence that the primary driver of these reductions is an improvement in work capacity, likely due to access to an additional form of pain management therapy. Institutional subscribers to the NBER working paper series, and residents of developing countries may download this paper without additional charge at www.nber.org.

Cannabis as Treatment for Chronic Pelvic Pain in Women: An Opportunity for the Cannabis Wellness Industry

In a healthcare landscape that routinely ignores women’s pain, many women turn to cannabis to manage their otherwise debilitating chronic pelvic pain caused by conditions such as endometriosis and polycystic ovary syndrome. This paper explores how the Controlled Substances Act wrongly characterized cannabis as having “no medicinal value” and the effects this federal illegality still has on women seeking alternative pain management therapies for chronic pelvic pain. Additionally, this paper explains why and how cannabis helps relieve such pain through discussing the effects of cannabinoids like THC and CBD on the body’s inflammatory response and the body’s endocannabinoid system. Women, as the leading consumers in our society, have expressed a need and a desire for products that provide relief from chronic pelvic pain and increase sexual pleasure. The 2018 Farm Bill opened the doors to CBD businesses looking to break into the women’s sexual and reproductive wellness market. The market for women-centric CBD pain relief and sexual enjoyment is far from saturated, and this paper encourages those in the CBD industry (or those looking to enter the industry) to take note.

Therapeutic Effectiveness of AxioBionics Wearable Therapy Pain Management System in Patients with Chronic Lower Back Pain.

Chronic lower back pain is one of the most common medical conditions leading to a significant decrease in quality of life. This study retrospectively analyzed whether the AxioBionics Wearable Therapy Pain Management (WTPM) System, a customized and wearable electrical stimulation device, alleviated chronic lower back pain, and improved muscular function. This study assessed self-reported pain levels using the visual analog scale before and during the use of the AxioBionics WTPM System when performing normal activities such as sitting, standing, and walking (n = 69). Results showed that both at-rest and activity-related pain were significantly reduced during treatment with the AxioBionics WTPM System (% reduction in pain: 64% and 60%, respectively; P < .05). Thus, this study suggests that the AxioBionics WTPM System is efficacious in treating chronic lower back pain even when other therapies have failed to sufficiently decrease reported pain levels.

Ağrı Yönetiminde Alternatif Bir Yaklaşım: Kahkaha Terapisi

Pain is defined by The International Association for the Study of Pain as an “unpleasant sensory, emotional and sensation or behavior pattern related to the past experiences of the individual associated with actual or potential tissue damage, originating from a certain part of the body”. There are pharmacological and nonpharmacological treatment methods for pain. Nonpharmacological treatment methods include pain training programs, exercise therapies, transcutaneous electrical stimulation, cognitive-behavioral therapies, acupuncture, massage techniques, hot-cold treatments, and relaxation exercises. Cognitive-behavioral strategies used in pain management are hypnosis, relaxation techniques, distraction. The laughter approach is one of the distraction techniques used in pain management. In the studies, the effects of laughter on rheumatic diseases, diabetes mellitus, allergic responses, immune system, cardiopulmonary disorders, cancers, aging problems, and pain were investigated. One of the non-pharmacological treatment methods used in pain management is laughter therapy. However, according to literature in our country, there are not enough studies that explain the place and importance of laughter therapy in pain management. Therefore, the purpose of the article; to review the concepts of pain and laughter therapy, laughter therapy in pain management, and its effects on pain.

Implementation of a Standardized Post-Cesarean Delivery Order Set with Multimodal Combination Analgesia Reduces Inpatient Opioid Usage.

Background: Opioid use has emerged as a leading cause of death in the US. Given that 1 in 300 opioid-naive patients exposed to opioids after cesarean birth will become persistent users, hospitals should strive to limit exposure to these medications. We set out to evaluate whether transitioning to a standardized order set based on multimodal combination analgesic therapy decreases the exposure to opioids after cesarean delivery. Methods: Our health system’s post-cesarean pain management electronic medical record (EMR) order set was changed from standing NSAIDs (Ibuprofen 600 mg every 6 h) and additional acetaminophen and opioid medications (Oxycodone 5 mg/acetaminophen 325 mg every 3 h or Oxycodone 10 mg/acetaminophen 650 mg every 6 h for moderate and severe pain, respectively) as needed (PRN) to a multimodal combination therapy with acetaminophen (975 mg every 6 h) and NSAIDs (Ibuprofen 600 mg every 6 h) as primary analgesics and opioids PRN (Oxycodone immediate release (IR) 5 mg every 3 h for moderate to severe pain). We performed a retrospective analysis across seven hospitals comparing inpatient opioid use, administration of other analgesics, and severe pain episodes (pain score ≥ 7) between the patients who were treated before and after implementation of the multimodal order set. Chi square and Student t-test were used for statistical analysis with significance determined as p < 0.05. Results: A total of 12,898 cesarean births were included (8696 prior and 4202 after implementation). The multimodal order set was associated with marked decrease in the incidence of post cesarean opioid use (45.4% vs. 67.5%; p < 0.0001), lower average opioid dose (26.7 mg vs. 36.6 mg of oxycodone; p < 0.0001), and increased dose of acetaminophen (8422 mg vs. 4563 mg; p < 0.0001), while severe pain scores were less frequent (46.3% vs. 56.6%, p < 0.0001). Conclusions: Multimodal analgesic therapy for post-cesarean pain management reduces inpatient opioid use while improving pain control. Incorporation of a multimodal order set as a default in the EMR facilitates effective and widespread implementation on a large scale. Obstetric units should consider standardizing post-cesarean pain management orders to include routine (not PRN) multimodal combination therapy with acetaminophen and NSAIDs as primary analgesics.

Enhanced Affinity for 3-Amino-Chromane-Derived σ1 Receptor Ligands.

The σ1 receptor is implicated in regulating a diverse range of physiology and is a target for developing therapies for cancer, pain management, neural degradation, and COVID-19. This report describes 36 phenethylamine-containing 3-amino-chromane ligands, which bind to σ1 with low nM affinities. The family consists of 18 distinct compounds and each enantiomer was independently assayed. Three compounds with the greatest affinity bind in the 2 nM Ki range (∼8.7 pKi). Furthermore, ligands with the (3R,4R) absolute stereochemistry on the 3-amino-chromane core have a higher affinity and greater σ1 versus TMEM97 selectivity. The most promising ligands were assayed in 661W cells, which did not show significant protective effects.