Objectives To develop and test two educational programmes (interactive and passive) aimed at improving family doctors' (FD) prescribing practices and patient's knowledge and use of non-opioid analgesics (NOA).Methods The educational programmes were conducted in two family medicine clinics by using a three-stage approach: baseline evaluation, design, and implementation of educational activities, and post-programme evaluation. An interactive educational programme (IEP) was compared with a passive educational programme (PEP); both were participated by FDs and patients. The IEP for FDs comprised (...) of workshops, discussion groups, in-service training and guidelines, while for patients the IEP consisted of an interactive session with a video, leaflets and a discussion. The PEP consisted in delivering the guidelines to the FDs and the leaflets to patients. The effect of the programmes on the FDs was measured through the appropriateness of prescriptions and analysed using the differences-in-differences estimator (D-in-D), and on patients through changes in self-medication and in their knowledge about the proper use and adverse events by analysing the inter- and intra-group differences before and after the programmes.Results The IEP obtained better results to improve appropriate FDs prescription of NOA than PEP (D-in-D = 15%). Regarding the patients, the PEP group reached higher reduction of self-medication than the IEP group (13.4% vs. 9.1%); the knowledge of proper NOA use increased by 8.5% in both groups, whereas knowledge of NOA-related adverse events was better in the IEP (39.6%) than in the PEP group (9.2%).Conclusions The IEP was better to improve the doctors' abilities to prescribe NOAs, and both programmes improved patients' knowledge. (shrink)

Pain management has improved in the past few decades. Opioid analgesics have become the mainstay in the treatment of cancer pain whilst inter-disciplinary pain management programmes are the generally accepted approach to chronic pain of non-malignant origin. Recently some pain specialists have advocated the use of opioids in the long-term management of non-cancer pain. This has raised some fundamental questions about the purpose of pain management. Is it best to opt for maximum pain relief and comfort, or should (...) one emphasise function and activity as higher priorities? Will the use of opioids create more autonomy for pain sufferers or will this add handicaps to lives which are already limited? Until more clinical outcome data are available we advocate caution in the use of opioid analgesia. Such caution can, and does, raise questions about the rights of the patient and the rights of the prescriber in a context where the facts do not point to a clear course of action. (shrink)

Overdose deaths involving prescription opioids killed more than 17,000 Americans in 2017, marking a five-fold increase since 1999. High prescribing rates of opioid analgesics have been a substantial contributor to prescription opioid misuse, dependence, overdose and heroin use. There was recognition approximately ten years ago that opioid prescribing patterns were contributing to this startling increase in negative opioid-related outcomes, and federal actions, including Medicare reimbursement reform and regulatory actions, were initiated to restrict opioid prescribing. (...) The current manuscript is a description of those actions, the effect of those actions on opioid prescribing and related patient outcomes. We also describe our proposal of methods of expanding these efforts as an important piece to further reduce opioid-related misuse, dependence, and overdose death. (shrink)

Over 100 million Americans suffer from chronic pain, which causes more disability than any other medical condition in the United States at a cost of $560–$635 billion per year. Opioid analgesics are frequently used to treat CP. However, long term use of opioids can cause brain changes such as opioid-induced hyperalgesia that, over time, increase pain sensation. Also, opioids fail to treat complex psychological factors that worsen pain-related disability, including beliefs about and emotional responses to pain. Cognitive (...) behavioral therapy can be efficacious for CP. However, CBT generally does not focus on important factors needed for long-term functional improvement, including attainment of personal goals and the psychological flexibility to choose responses to pain. Acceptance and Commitment Therapy has been recognized as an effective, non-pharmacologic treatment for a variety of CP conditions. However, little is known about the neurologic mechanisms underlying ACT. We conducted an ACT intervention in women with chronic musculoskeletal pain. Functional magnetic resonance imaging data were collected pre- and post-ACT, and changes in functional connectivity were measured using Network-Based Statistics. Behavioral outcomes were measured using validated assessments such as the Acceptance and Action Questionnaire, the Chronic Pain Acceptance Questionnaire, the Center for Epidemiologic Studies Depression Scale, and the NIH Toolbox Neuro-QoLTM scales. Results suggest that, following the 4-week ACT intervention, participants exhibited reductions in brain activation within and between key networks including self-reflection, emotion, and cognitive control. These changes in connectivity strength were correlated with changes in behavioral outcomes including decreased depression and pain interference, and increased participation in social roles. This study is one of the first to demonstrate that improved function across the DMN, SN, and FPN may drive the positive outcomes associated with ACT. This study contributes to the emerging evidence supporting the use of neurophysiological indices to characterize treatment effects of alternative and complementary mind-body therapies. (shrink)

In order to receive controlled pain medications for chronic non-oncologic pain, patients often must sign a “narcotic contract” or “opioid treatment agreement” in which they promise not to give pills to others, use illegal drugs, or seek controlled medications from health care providers. In addition, they must agree to use the medication as prescribed and to come to the clinic for drug testing and pill counts. Patients acknowledge that if they violate the opioid treatment agreement, they may no (...) longer receive controlled medications. OTAs have been widely implemented since they were recommended by multiple national bodies to decrease misuse and diversion of narcotic medications. But critics argue that OTAs are ethically suspect, if not unethical, and should be used with extreme care if at all. We agree that OTAs pose real dangers and must be implemented carefully. But we also believe that the most serious criticisms stem from a mistaken understanding of OTAs’ purpose and ethical basis. (shrink)

The national opioid epidemic is severely impacting Indian Country. In this article, we draw upon data from the Centers for Disease Control and Prevention to describe the contours of this crisis among Native Americans. While these data are subject to significant limitations, we show that Native American opioid overdose mortality rates have grown substantially over the last seventeen years. We further find that this increase appears to at least parallel increases seen among non-Hispanic whites, who are often thought (...) to be uniquely affected by this crisis. We then profile tribal medical and legal responses to the opioid epidemic, ranging from tribally-operated medication-assisted therapy to drug diversion courts rooted in traditional tribal cultures. (shrink)

Patients living with chronic pain require appropriate access to opioid therapy along with improved access to pain care and additional therapeutic options. It's both medically reasonable and ethical to consider opioid therapy as a treatment option in the management of chronic, non-cancer pain for a subset of patients with severe pain that is unresponsive to other therapies, negatively impacts function or quality of life, and will likely outweigh the potential harms. This paper will examine opioid therapy in (...) the setting of the opioid epidemic, why critics feel that the CDC guideline has resulted in harsh consequences for patients and their physicians, and the rationale for opioid therapy as a means of providing ethical and compassionate pain care. (shrink)

Identifying the role of opioids in the mediation of learned sexual behaviors has been complicated by the use of differing methodologies in the investigations. In this review addressing multiple species, techniques, and pharmaceutical manipulations, several features of opioid mediation become apparent. Opioids are differentially involved in conditioned and unconditioned sexual behaviors. The timing of the delivery of a sexual reinforcer during conditioning trials, especially those using male subjects, acutely influences the role that opioids have in learning. Opioids may be (...) particularly important in the maintenance of conditioned sexual behaviors during periods of non-reinforcement. This appears to be true both for probe trials and procedures designed explicitly to extinguish a sexual conditioned response. These features of opioid mediation of learning do not appear to be restricted to sexual conditioning paradigms. This suggests that, as for other aspects of sexual learning that despite distinctive features conform to underlying behavioral principles, the mediation of conditioned sexual behavior by opioids relies on processes common across reinforcement systems. Keywords: opiate; conditioning; extinction; persistence; naloxone; learning (Published: 15 March 2012) Citation: Socioaffective Neuroscience & Psychology 2012, 2 : 14874 - DOI: 10.3402/snp.v2i0.14874. (shrink)

The spinal mechanisms of action of opioids under normal conditions are reasonably well understood. The spinal effects of opioids can be enhanced or reduced depending on pathology and activity in other segmental and nonsegmental pathways. This plasticity will be considered in relation to the control of different pain states using opioids. The complex and contradictory findings on the supraspinal actions of opioids are explicable in terms of heterogeneous descending pathways to different spinal targets using multiple transmitters and receptors – therefore (...) opioids can both increase and decrease activity in descending pathways. These pathways could exhibit considerable plasticity. There is increasing evidence that delta opioid receptor agonists have the potential to replace morphine as major analgesics with reduced side-effect profiles. The concept of preemptive analgesia, based on preventing the induction of some of the negative plastic influences on opioid controls and the detrimental effects of pain, is sound, but experimental verification in the clinical setting is difficult. For example, a delayed compensatory upregulation of inhibitory systems, particularly in inflammation, may counter persistent painful inputs. Combination therapy with opioids may be beneficial in many pain states where either negative influences are blocked or inhibitory controls are enhanced. Finally, developmental aspects of these systems are discussed in connection with the treatment of pain in young children, where inhibitory systems in the spinal cord are immature. (shrink)

In this book, public health ethicist Daniel S. Goldberg sets out to characterize the subjective experience of pain and its undertreatment within the US medical establishment, and puts forward public policy recommendations for ameliorating the undertreatment of pain. The book begins from the position that the overwhelming focus on opioid analgesics as a means for improving the undertreatment of pain is flawed, and argues instead that dominant Western models of biomedicine and objectivity delegitimize subjective knowledge of the body (...) and pain in the US. This general intolerance for the subjectivity of pain is part of a specific American culture of pain in which a variety of actors take part, including not only physicians and health care providers, but also pain sufferers, caregivers, and policymakers. Concentrating primarily on bioethics, history, and public policy, the book brings a truly interdisciplinary approach to an urgent practical ethical problem. Taking up the practical challenge, the book culminates in a series of policy recommendations that provide pathways for moral agents to move beyond contests over drug policy to policy arenas that, based on the evidence, hold more promise in their capacity to address the devastating and inequitable undertreatment of pain in the US. (shrink)

At the end of life, pain management is commonly a fundamental part of the treatment plan for patients where curative measures are no longer possible. However, the increased recognition of opioid diversion for secondary gain coupled with efforts to treat patients in the home environment towards the end of life creates the potential for ethical dilemmas in the palliative care management of terminal patients in need of continuous pain management. We present the case of an end-stage patient with rectal (...) cancer who required a continuous residential narcotic infusion of fentanyl for pain control due to metastatic disease. His functional status was such that he had poor oral intake and ability to perform other activities of daily living, but was able to live at home with health agency nursing care. The patient presented to this institution with a highly suspect history of having lost his fentanyl infusion in a residential accident and asking for a refill to continue home therapy. The treating physicians had concerns of diversion of the infusion medication by caregivers and were reluctant to continue the therapeutic relationship with the patient. This case exemplifies the tension that can exist between wanting to continue with palliative care management of an end-stage patient and the fear of providers when confronted by evidence of potential diversion of opioid analgesic medications. We elucidate how an ethical framework based on a combination of virtue and narrative/relationship theories with reference to proportionality can guide physicians to a pragmatic resolution of these difficult situations. (shrink)

This paper traces the unspoken, implicit white racial logic of the brain disease model of addiction, which is based on seemingly universal, disembodied brains devoid of social or environmental influences. In the United States, this implicit white logic led to “context-free” neuroscience that made the social hierarchies of addiction and its consequences invisible to, and thus exacerbated by, national policies on opioids. The brain disease model of addiction was selectively deployed among the white middle-class population that had long accessed narcotics (...) and pharmaceutical treatments for narcotics disorders from biomedical clinics, as opposed to from illegal sources subject to law enforcement. In turn, new treatments for opioid addiction were racially marketed to the same white clientele to which newly patented opioid analgesics were marketed, tapping into a circumscribed but highly lucrative consumer base that has long benefited from a legally protected, racially segregated safe space for white narcotics consumption. The connecting thread for the contemporary white opioid “crisis,” therefore, is white race as a ghost variable in addiction neuroscience and in its pharmaceutical and biotechnological translation. (shrink)

dickenson briefly mentions that peripheral opioid receptors somehow become active following inflammation and that the appearance of endogenous opioid peptides at the injury site may be related to immune cell proliferation. Recent findings elucidate the underlying mechanisms in more detail and provide an incentive for the development of a novel generation of analgesics devoid of typical central opioid side effects.

Introduction: Neurobiological systems engineering models are useful for treating patients. We show a model of “high opioid tone” autism and present a hypothesis about how autism is caused by administration of opioids during childbirth.Main Symptoms: Clinical diagnosis of autism in a 25 year old man was confirmed by a Social Responsiveness Scale self-rating of 79, severe, and a Social Communications Questionnaire by the patient's father scoring 27. Cold pressor time was 190 seconds—unusually long, consonant with the high pain tolerance (...) of autism.Therapeutic Intervention and Outcomes: At naltrexone 50 mg/day SRS fell to 54 and SCQ-−2–9; both non-significant. CPT fell to 28, repeat 39 s. Improved relatedness was experienced ambivalently, understood as feelings never before experienced—causing pain. Non-compliance with naltrexone was followed by cutting open his palm and drinking alcoholically. Transference focused psychotherapy has helped him remain naltrexone—compliant while he works on issues of identity and relatedness.Conclusion: The model suggests studies that could be conducted to both prevent and treat this form of autism. (shrink)

There has been much debate regarding the 'double-effect' of sedatives and analgesics administered at the end-of-life, and the possibility that health professionals using these drugs are performing 'slow euthanasia.' On the one hand analgesics and sedatives can do much to relieve suffering in the terminally ill. On the other hand, they can hasten death. According to a standard view, the administration of analgesics and sedatives amounts to euthanasia when the drugs are given with an intention to hasten (...) death. In this paper we report a small qualitative study based on interviews with 8 Australian general physicians regarding their understanding of intention in the context of questions about voluntary euthanasia, assisted suicide and particularly the use of analgesic and sedative infusions (including the possibility of voluntary or non-voluntary 'slow euthanasia'). We found a striking ambiguity and uncertainty regarding intentions amongst doctors interviewed. Some were explicit in describing a 'grey' area between palliation and euthanasia, or a continuum between the two. Not one of the respondents was consistent in distinguishing between a foreseen death and an intended death. A major theme was that 'slow euthanasia' may be more psychologically acceptable to doctors than active voluntary euthanasia by bolus injection, partly because the former would usually only result in a small loss of 'time' for patients already very close to death, but also because of the desirable ambiguities surrounding causation and intention when an infusion of analgesics and sedatives is used. The empirical and philosophical implications of these findings are discussed. (shrink)

The number of police departments carrying Narcan keeps increasing at a fast pace throughout the U.S., as it is considered an effective measure to fight the opioid epidemic. However, there have been strong oppositions to the idea of the police Narcan use. Still, in 2018, the nation is debating about it. Though not clearly visible to the public, there are important ethical arguments against the police Narcan use which necessarily involve understanding of the ethical roles and responsibilities of police (...) as the law enforcement agency and apprehension of the moral status of a non-therapeutic opioid use. The authors of the paper investigate, primarily, the existing ethical controversies surrounding the police Narcan use while touching upon the issue of the decriminalizing drug policy in the U.S. The authors conclude that the police can carry and administer Narcan without self-contradiction and that the policymakers’ investigation on the drug decriminalization policy should begin with the understanding of the “common morality” of the American public, the ethical view shared and practiced by the greatest number of people. (shrink)

Maternal opioid use during pregnancy is a growing national problem and can lead to newborns developing neonatal opioid withdrawal syndrome soon after birth. Recent data demonstrates that nearly every 15 min a baby is born in the United States suffering from NOWS. The primary treatment for NOWS is opioid replacement therapy, commonly oral morphine, which has neurotoxic effects on the developing brain. There is an urgent need for non-opioid treatments for NOWS. Transcutaneous auricular neurostimulation, a novel (...) and non-invasive form of electrostimulation, may serve as a promising alternative to morphine. tAN is delivered via a multichannel earpiece electrode worn on and around the left ear, targeting two cranial nerves—the vagus and trigeminal nerves. Prior research suggests that auricular neurostimulation exerts an anxiolytic effect on the body by releasing endogenous opioids and reduces withdrawal symptoms in adults actively withdrawing from opioids. In this first-in-human prospective, open-label trial, we investigated tAN as an adjuvant to morphine therapy in eight infants >33 weeks gestational age suffering from NOWS and receiving oral morphine treatment. Infants received tAN for 30 min 1 h before receiving a morphine dose. tAN was delivered at 0.1 mA below perception intensity at two different nerve targets on the ear: Region 1, the auricular branch of the vagus nerve; and Region 2, the auriculotemporal nerve. tAN was delivered up to four times daily for a maximum of 12 days. The primary outcome measures were safety [heart rate monitoring, Neonatal Infant Pain Scale, and skin irritation] and morphine length of treatment. tAN was well-tolerated and resulted in no unanticipated adverse events. Comparing to the national average of 23 days, the average oral morphine LOT was 13.3 days and the average LOT after tAN initiation was 7 days. These preliminary data suggest that tAN is safe and may serve as a promising alternative adjuvant for treating NOWS and reducing the amount of time an infant receives oral morphine. (shrink)

Physicians generally recommend that patients resuscitated with naloxone after opioid overdose stay in the emergency department for a period of observation in order to prevent harm from delayed sequelae of opioid toxicity. Patients frequently refuse this period of observation despiteenefit to risk. Healthcare providers are thus confronted with the challenge of how best to protect the patient’s interests while also respecting autonomy, including assessing whether the patient is making an autonomous choice to refuse care. Previous studies have shown (...) that physicians have widely divergent approaches to navigating these conflicts. This paper reviews what is known about the effects of opioid use disorder on decision-making, and argues that some subset of these refusals are non-autonomous choices, even when patients appear to have decision making capacity. This conclusion has several implications for how physicians assess and respond to patients refusing medical recommendations after naloxone resuscitation. (shrink)

The opioid crisis has greatly increased the number of patients who are illegally injecting drugs while hospitalized for other conditions. Physicians face a difficult decision in these circumstances: when is it appropriate to involuntarily discharge or “fire” a patient with opioid use disorder for their continued nonmedical use of opioids? This commentary analyzes physicians’ responsibilities to their patients and argues that physicians should fire non-adherent patients only when every other option has been exhausted and the expected benefits of (...) firing the patient outweigh the expected harms. (shrink)

While the prevalence of opioid use disorder among pregnant women has multiplied in the United States in the last decade, buprenorphine treatment for peripartum women with OUD has been administered to reduce risks of repeated cycles of craving and withdrawal. However, the maternal behavior and bonding in mothers with OUD may be altered as the underlying maternal behavior neurocircuit is opioid sensitive. In the regulation of rodent maternal behaviors such as licking and grooming, a series of opioid-sensitive (...) brain regions are functionally connected, including the ventral pallidum. In humans, these brain regions, interact with the supplementary motor area to regulate maternal behaviors and are functionally dysregulated by opioids. It is unclear how these brain regions respond to the emotions of their child for mothers receiving BT. In this functional magnetic resonance imaging pilot study in 22 mothers within the first postpartum year, including six mothers receiving BT and 16 non-OUD mothers as a comparison group, we devised a child face mirroring task in fMRI settings to assess maternal responses to pictures of facial expressions of own child and an unknown child in an empathic mirroring condition and a non-mirroring observation condition. In each condition, faces of neutral, ambiguous, distressed, and joyful expressions of each child were repeatedly displayed in a random order. The response of SMA during empathic mirroring vs. non-mirroring of own child was reduced among BT/OUD vs. CG. Within MBN, the left VP, critical for parental sensitivity, had a similar deficit. This study outlines potential mechanisms for investigating the risks of deficits in the neural responses to actual maternal sensitivity and parenting behavior in mothers with OUD, and potential targets for interventions that reduce stress and augment maternal behavior and child outcome. (shrink)

BackgroundAs opioid use disorder (OUD) incidence and its associated deaths continue to persist at elevated rates, the development of novel treatment modalities is warranted. Recent strides in this therapeutic area include novel anti-opioid vaccine approaches. This work compares logistical and ethical considerations surrounding currently available interventions for opioid use disorder with an anti-opioid vaccine approach.MethodsThe opinions of student pharmacists and practicing pharmacists assessing knowledge, perceptions, and attitudes toward current and future OUD management strategies were characterized using (...) a staged, multi-modal research approach incorporating a focus group, pilot survey development and refinement, and final survey deployment. Survey responses were assessed using one- and two-way parametric and non-parametric analyses where appropriate, and multi-dimensional matrix profiles were compared using z-tests following an exhaustive combinatorial sum of differences calculation between items within each compared matrix.ResultsFocus group content analysis revealed a high level of agreeableness among participants regarding anti-opioid vaccine technology and a sense of shared ownership regarding solutions to the opioid epidemic at large. Pilot survey results demonstrated subject ability to consider both pragmatic and ethical considerations related to current therapeutics and novel interventions in a single instrument, with high endurance amongst engaged subjects. Access inequality was the most concerning ethical consideration identified for anti-opioid vaccines. Support for anti-opioid vaccine implementation across various clinical scenarios was strongest for voluntary use amongst individuals in recovery, and lowest for mandatory use in at-risk individuals.ConclusionsEthical and logistical concerns surrounding anti-opioid vaccines were largely similar to those for current OUD therapeutics overall. Anti-opioid vaccines were endorsed as helpful potential additions to current OUD therapeutic approaches, particularly for voluntary use in the later stages of clinical progression. (shrink)

My essay ‘Weakening the ethical distinction between euthanasia, palliative opioid use and palliative sedation’ has recently generated some critique which I will attempt to address in this response. Regarding the empirical question of whether palliative opioid and sedative use shorten survival time, Schofield et al raise the three concerns that my literature review contains a cherry-picking bias through focusing solely on the palliative care population, that continuous deep palliative sedation falls beyond the scope of routine palliative care, and (...) that my research may contribute to opiophobia and be harmful to palliative care provision globally. Materstvedt argues that euthanasia ‘ends’ rather than ‘relieves’ suffering and is not a treatment, and that the arguments in my essay are therefore predicated on a ‘category mistake’ and are a non-starter. Symons and Giebel both raise the concern that my Kantian and Millian interpretation of the Doctrine of Double Effect is anachronistic, and that when interpreted from the contemporaneous perspective of Aquinas it is a sound ethical principle. Giebel also argues that palliative opioid and sedative use do meet the Doctrine of Double Effect’s four criteria on this Thomistic account, and that it does not contradict the Doctrine of the Sanctity of Human Life. In this response I will explore and defend against most of these claims, in doing so clarifying my original argument that the empirical and ethical differences between palliative opioid/sedative use and euthanasia may not be as significant as often believed, thereby advancing the case for euthanasia. (shrink)

Drug overdose has recently surpassed motor vehicle accidents to become the leading cause of unintentional injury death in the United States. The epidemic is largely driven by opioids such as oxycodone, hydrocodone, and methadone, which kill more Americans than heroin and cocaine combined. The demographics of overdose have changed over the past few decades as well: according to the latest data, the average overdose victim is now a non-Hispanic white man aged 45-54.These deaths — over 16,000 per year — are (...) almost entirely preventable. Opioid overdose kills by slowly depressing respiration, a process that can take several hours. It can be quickly and effectively reversed by the timely administration of naloxone, an opioid antagonist that works by displacing opioids from the brain receptors to which they attach, reversing their depressant effect. Naloxone, also known as Narcan, has many benefits and minimal risks. Although it is a prescription drug, it is not a controlled substance and has no abuse potential. (shrink)

Despite shifts in rhetoric and some positive movement, Americans with the disease of addiction are still often stigmatized, criminalized, and denied access to evidencebased care. Dramatically reducing the number of lives unnecessarily lost to overdose requires an evidence-based, equity-focused, well-funded, and coordinated response. We present in this brief article evidence-based and promising practices for improving and refocusing the response to this simmering public health crisis. Topics covered include improving clinical decision-making, improving access to non-judgmental evidence-based treatment, investing in comprehensive public (...) health approaches to problematic drug use, and changing the way law enforcement actors interact with people who use drugs. (shrink)

Marshall et al. (2024) persuasively argue that some patients with opiate use disorder (OUD), who refuse observation after naloxone resuscitation in the emergency department (ED), “may be making non...

Although activated spinal cord glia contribute importantly to neuropathic pain, how nerve injury activates glia remains controversial. It has recently been proposed, on the basis of genetic approaches, that toll-like receptor 4 may be a key receptor for initiating microglial activation following L5 spinal nerve injury. The present studies extend this idea pharmacologically by showing that TLR4 is key for maintaining neuropathic pain following sciatic nerve chronic constriction injury. Established neuropathic pain was reversed by intrathecally delivered TLR4 receptor antagonists derived (...) from lipopolysaccharide. Additionally, -naltrexone, -naloxone, and -naloxone, which we show here to be TLR4 antagonists in vitro on both stably transfected HEK293-TLR4 and microglial cell lines, suppressed neuropathic pain with complete reversal upon chronic infusion. Immunohistochemical analyses of spinal cords following chronic infusion revealed suppression of CCI-induced microglial activation by -naloxone and -naloxone, paralleling reversal of neuropathic pain. Together, these CCI data support the conclusion that neuron-to-glia signaling through TLR4 is important not only for initiating neuropathic pain, as suggested previously, but also for maintaining established neuropathic pain. Furthermore, these studies suggest that the novel TLR4 antagonists -naloxone and -naloxone can each fully reverse established neuropathic pain upon multi-day administration. This finding with -naloxone is of potential clinical relevance. This is because -naloxone is an antagonist that is inactive at the -opioid selective receptors on neurons that produce analgesia. Thus, these data suggest that -opioid antagonists such as -naloxone may be useful clinically to suppress glial activation, yet -opioid agonists suppress pain. (shrink)

A study of the constitution and development of the human being from the metaphysical point of view, with special reference to Vedantic doctrine.

The Reign of Quantity gives a concise but comprehensive view of the present state of affairs in the world, as it appears from the point of view of the 'ancient wisdom', formerly common both to the East and to the West, but now almost entirely lost sight of. The author indicates with his fabled clarity and directness the precise nature of the modern deviation, and devotes special attention to the development of modern philosophy and science, and to the part played (...) by them, with their accompanying notions of progress and evolution, in the formation of the industrial and democratic society which we now regard as 'normal'. Guénon sees history as a descent from Form (or Quality) toward Matter (or Quantity); but after the Reign of Quantity-modern materialism and the 'rise of the masses'-Guénon predicts a reign of 'inverted quality' just before the end of the age: the triumph of the 'counter-initiation', the kingdom of Antichrist. This text is considered the magnum opus among Guénon's texts of civilizational criticism, as is Symbols of Sacred Science among his studies on symbols and cosmology, and Man and His Becoming according to the Vedanta among his more purely metaphysical works. (shrink)

Description: Contents: Preface 1. General Remarks on the Vedanta 2. Fundamental Distinction Between The Self and the Ego 3. The Vital Centre of the Human Being, Seat of Brahma 4. Purusha and Prakriti 5. Purusha Unaffected by Individual Modifications 6. The Degrees of Individual Manifestation 7. Buddhi or the Higher Intellect 8. Manas or the Inward Sense : The Ten External Faculties of Sensation and Action 9. The Envelopes of the Self ; The Five Vayus or Vital Functions 10. The (...) Essential Unity and Identity of the Self in all the States of the Being 11. The Different Conditions of Atma in the Human Being 12. The Waking State or the Condition of Vaishwanara 13. The Dream State or the Condition of Taijasa 14. The State of Deep Sleep or the Condition of Prajna 15. The Unconditioned State of Atma 16. The Symbolical Representation of Atma and its Conditions by the Sacred Monosyllable Om 17. The Posthumous Evolution of the Human Being 18. The Reabsorption of the Individual Faculties 19. Differences in the Posthumous Conditions According to the Degrees of Knowledge 20. The Coronal Artery and the Solar Ray 21. The Divine Journey of the Being on the Path of Liberation 22. Final Deliverance 23. Videha-mukti and Jivana-mukti 24. The Spiritual State of the Yogi : The Supreme Identity. (shrink)

QUALITY AND QUANTITY are fairly generally regarded as complementary terms, although the profound reason for their comple- mentarism is often far from being understood, this reason lying in the 'polar' correspondence referred to toward ...

The concluding chapter lays down the essential conditions for any genuine understanding between East and West, which can only come through the work of those who have attained, at least in some degree, to the realization of 'wisdom uncreate' ...

Buddhist concepts of personal life and responsibilities.

Physicians’ fear of criminal prosecution for prescribing opioid analgesics is a major reason why many chronic pain patients are having an increasingly difficult time obtaining medically appropriate pain relief. In Ruan v. United States, 142 S. Ct. 2370 (2022), the Supreme Court unanimously vacated two federal convictions under the Controlled Substances Act. The Court held that the government must prove that the defendant knowingly or intentionally acted in an unauthorized manner.