Managing chronic pain patients at the time of covid-19 pandemic

COVID-19 is imposing unprecedented stress on our healthcare system but in some cases these changes, such as more telemedicine for pain management, may be valuable paradigm shifts that shape the future of modern medicine. Pain does not stop for the pandemic and pain care must continue as well

Naldemedine. A new option for OIBD

Opioid-induced bowel dysfunction (OIBD) is a common complication in long-term opioid users and abusers. It is a burdensome condition, which significantly limits quality of life and is associated with increasing health costs. OIBD affects up to 60% of patients with chronic non-cancer pain and over 80% of patients suffering from cancer pain and is one of the conditions of the most common symptoms associated with opioid main-tenance. Given the continued use of opioids for chronic pain management in appropriate patients, OIBD is likely to persist in clinical practice in the coming years. We will herein review its underlying pathophysiological mechanisms and the available treatments. In the last years, pharmaceutical research has focused on the opportunity of targeting peripheral mu-opioid receptors without affecting their analgesic activity in the central nervous system, and several peripherally acting mu-opioid receptors antagonists (PAMORAs) drugs have been approved. We will mainly focus on naldemedine, discussing its pharmacological properties, its clinical efficacy and side effects. Head-to-head comparisons between naldemedine and the other PAMORAs are not available yet, but some considerations will be discussed based on the pharmacological and clinical data. As a whole, the available data suggest that naldeme-dine is a valid treatment option for OIBD, as it is a well-tolerated drug that alleviates constipation without affecting analgesia or causing symptoms of opioid withdrawal

Tapentadol. An effective option for the treatment of back pain

Back pain, including low back pain and neck pain, is the leading cause of disability worldwide. This type of pain is challenging to treat, since it presents both a nociceptive and a neuropathic component. The latter also contributes to the evolution of pain toward chronification. Treatment selection should therefore consider the ability to prevent this event. Tapentadol is characterized by a unique and innovative peculiar mechanism of action that makes it the first representative of a new class of central strong analgesics referred to as MOR-NRI. This molecule acts both on the nociceptive and neuropathic components of pain, and it can therefore be effective in the treatment of a mixed pain condition such as back pain. This narrative review discusses the rationale for the use of tapentadol in both low back pain and neck pain and presents available clinical data. Overall, data show that tapentadol prolonged release is a well-grounded treatment for chronic back pain, sustained by a strong mechanistic rationale and robust evidence. Given also the availability of long-term efficacy and safety data, we believe that this molecule should be considered as an elective therapy for chronic back pain

Potential energy landscape of finite-size mean-field models for glasses

connected spin-glass models with a discontinuous transition. In the thermodynamic limit the equilibrium properties in the high temperature phase are described by the schematic Mode Coupling Theory of super-cooled liquids. We show that {\it finite-size} fully connected spin-glass models do exhibit properties typical of Lennard-Jones systems when both are near the critical glass transition, where thermodynamics is ruled by energy minima distribution. Our study opens the way to consider activated processes in real glasses through finite-size corrections (i.e. calculations beyond the saddle point approximation) in mean-field spin-glass models.Comment: 8 pages, 3 postscript figures, EPL format, improved versio

The challenge of perioperative pain management in opioid-tolerant patients

The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone

Using opioid therapy for pain in clinically challenging situations. Questions for clinicians

Healthcare professionals and organizations increasingly face the conundrum of treating patients with active substance use disorder, a history of personal or familial substance use disorder, or those at elevated risk for substance abuse. Such patients need compassionate care when facing painful conditions; in fact, denying them pain control makes it likely that they will seek out ways to self-medicate with illicit drugs. Yet it remains unclear how to safely and effectively treat patients in these challenging situations. The authors have formulated ten questions to address in order to provide adequate analgesia for such patients. These questions demand a highly individualized approach to analgesia. These ten questions involve understanding the painful condition (presumed trajectory, duration, type of pain), using validated metrics such as risk assessment tools, guidelines, protocols, and safeguards within the system, selection of the optimal analgesic product(s) or combination therapy, and never starting opioid therapy without clear treatment objectives and a definitive exit plan. It is tempting but inaccurate to label these individuals as “inappropriate patients,” rather they are high-risk individuals in very challenging clinical situations. The challenge is that both options — being in pain or being treated with opioids to control pain — expose the patient to a risk of rekindling an addiction. The question is how do we, as clinicians, adequately respond to these very perplexing clinical challenges

Liquid Limits: The Glass Transition and Liquid-Gas Spinodal Boundaries of Metastable Liquids

The liquid-gas spinodal and the glass transition define ultimate boundaries beyond which substances cannot exist as (stable or metastable) liquids. The relation between these limits is analyzed {\it via} computer simulations of a model liquid. The results obtained indicate that the liquid - gas spinodal and the glass transition lines intersect at a finite temperature, implying a glass - gas mechanical instability locus at low temperatures. The glass transition lines obtained by thermodynamic and dynamic criteria agree very well with each other.Comment: 5 pages, 4 figures, to appear in Phys. Rev. Let

Statistical Physics of Structural Glasses

This paper gives an introduction and brief overview of some of our recent work on the equilibrium thermodynamics of glasses. We have focused onto first principle computations in simple fragile glasses, starting from the two body interatomic potential. A replica formulation translates this problem into that of a gas of interacting molecules, each molecule being built of $m$ atoms, and having a gyration radius (related to the cage size) which vanishes at zero temperature. We use a small cage expansion, valid at low temperatures, which allows to compute the cage size, the specific heat (which follows the Dulong and Petit law), and the configurational entropy. The no-replica interpretation of the computations is also briefly described. The results, particularly those concerning the Kauzmann tempaerature and the configurational entropy, are compared to recent numerical simulations.Comment: 21 pages, 6 figures, to appear in the proceedings of the Trieste workshop on "Unifying Concepts in Glass Physics