Tryptophan (TRP) is an essential, aromatic amino acid catabolized by indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) enzymes into kynurenine. The IDO enzyme is expressed in ...peripheral tissues and the central nervous system. Another enzyme of interest in the kynurenine signaling pathway is kynurenine 3-monooxygenase (KMO). The purpose of this review is to discuss the role of TRP and the kynurenine signaling pathway in different chronic pain patients. The IDO-1, IDO-2, and KMO enzymes and the kynurenine metabolite have been shown to be involved in the pathogenesis of neuropathic pain and other painful conditions (migraine, cluster headache, etc.) as well as depressive behavior. We highlighted the analgesic potential of novel agents targeting the enzymes of the kynurenine signaling pathway to explore their efficacy in both future basic science and transitional studies. Upcoming studies conducted on animal models will need to take into consideration the differences in TRP metabolism between human and non-human species. Since chronic painful conditions and depression have common pathophysiological patterns, and the kynurenine signaling pathway is involved in both of them, future clinical studies should aim to have outcomes targeting not only pain, but also functionality, mood changes, and quality of life.
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Ovarian hormones play an important role in pain perception, and are responsible, at least in part, for the pain threshold differences between the sexes. Modulation of pain and its perception are ...mediated by neurochemical changes in several pathways, affecting both the central and peripheral nervous systems. One of the most studied neurotransmitters related to pain disorders is serotonin. Estrogen can modify serotonin synthesis and metabolism, promoting a general increase in its tonic effects. Studies evaluating the relationship between serotonin and disorders such as irritable bowel syndrome, fibromyalgia, migraine, and other types of headache suggest a clear impact of this neurotransmitter, thereby increasing the interest in serotonin as a possible future therapeutic target. This literature review describes the importance of substances such as serotonin and ovarian hormones in pain perception and illustrates the relationship between those two, and their direct influence on the presentation of the aforementioned pain-related conditions. Additionally, we review the pathways and receptors implicated in each disorder. Finally, the objective was to stimulate future pharmacological research to experimentally evaluate the potential of serotonin modulators and ovarian hormones as therapeutic agents to regulate pain in specific subpopulations.
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It is estimated that the total annual financial cost for pain management in the U.S. exceeds 100 billion dollars. However, when indirect costs are included, such as functional disability and ...reduction in working hours, the cost can reach more than 300 billion dollars. In chronic pain patients, the role of pharmacogenetics is determined by genetic effects on various pain types, as well as the genetic effect on drug safety and efficacy. In this review article, we discuss genetic polymorphisms present in different types of chronic pain, such as fibromyalgia, low back pain, migraine, painful peripheral diabetic neuropathy and trigeminal neuralgia. Furthermore, we discuss the role of CYP450 enzymes involved in metabolism of drugs, which have been used for treatment of chronic pain (amitriptyline, duloxetine, opioids, etc.). We also discuss how pharmacogenetics can be applied towards improving drug efficacy, shortening the time required to achieve therapeutic outcomes, reducing risks of side effects, and reducing medical costs and reliance upon polypharmacy.
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Back pain is the second leading cause of disability among American adults and is currently treated either with conservative therapy or interventional pain procedures. However, the question that ...remains is whether we, as physicians, have adequate therapeutic options to offer to the patients who suffer from chronic low back pain but fail both conservative therapy and interventional pain procedures before they consider surgical options such as discectomy, disc arthroplasty, or spinal fusion. The purpose of this article is to review the potential novel therapies that are on the horizon for the treatment of chronic low back pain. We discuss medications that are currently in use through different phases of clinical trials (I-III) for the treatment of low back pain. In this review, we discuss revisiting the concept of chemonucleolysis using chymopapain, as the first drug in an intradiscal injection to reduce herniated disc size, and newer intradiscal therapies, including collagenase, chondroitinase, matrix metalloproteinases, and ethanol gel. We also review an intravenous glial cell-derived neurotrophic growth factor called artemin, which may repair sensory nerves compressed by herniated discs. Another new drug in development for low back pain without radiculopathy is a subcutaneous monoclonal antibody acting as nerve growth factor called tanezumab. Finally, we discuss how platelet-rich plasma and stem cells are being studied for the treatment of low back pain. We believe that with these new therapeutic options, we can bridge the current gap between conservative/interventional procedures and surgeries in patients with chronic back pain.
Complementary and alternative medicines such as herbal medicines are not currently part of the conventional medical system. As the popularity of and global market for herbal medicine grows among all ...age groups, with supporting scientific data and clinical trials, specific alternative treatments such as herbal medicine can be reclassified as a practice of conventional medicine. One of the most common conditions for which adults use herbal medicine is pain. However, herbal medicines carry safety concerns and may impact the efficacy of conventional therapies. Unfortunately, mechanisms of action are poorly understood, and their use is unregulated and often underreported to medical professionals. This review aims to compile common and available herbal medicines which can be used as an alternative to or in combination with conventional pain management approaches. Efficacy and safety are assessed through clinical studies on pain relief. Ensuing herb-drug interactions such as cytochrome modulation, additive and synergistic effects, and contraindications are discussed. While self-management has been recognized as part of the overall treatment strategy for patients suffering from chronic pain, it is important for practitioners to be able to also optimize and integrate herbal medicine and, if warranted, other complementary and alternative medicines into their care.
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Quantum wells formed by layers of HgTe between HgFormula: see textCdFormula: see textTe barriers lead to two-dimensional (2D) topological insulators, as predicted by the BHZ model. Here, we ...theoretically and experimentally investigate the characteristics of triple HgTe quantum wells. We describe such heterostructure with a three dimensional Formula: see text Kane model, and use its eigenstates to derive an effective 2D Hamiltonian for the system. From these we obtain a phase diagram as a function of the well and barrier widths and we identify the different topological phases composed by zero, one, two, and three sets of edge states hybridized along the quantum wells. The phase transitions are characterized by a change of the spin Chern numbers and their corresponding band inversions. Complementary, transport measurements are experimentally investigated on a sample close to the transition line between the phases with one and two sets of edges states. Accordingly, for this sample we predict a gapless spectrum with low energy bulk conduction subbands given by one parabolic and one Dirac subband, and with edge states immersed in the bulk valence subbands. Consequently, we show that under these conditions, local and non-local transport measurements are inconclusive to characterize a sole edge state conductivity due to bulk conductivity. On the other hand, Shubnikov-de Haas (SdH) oscillations show an excellent agreement with our theory. Particularly, we show that the measured SdH oscillation frequencies agrees with our model and show clear signatures of the coexistence of a parabolic and Dirac subbands.
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CoronaVac is an inactivated SARS-CoV-2 vaccine that has been rolled out in several low and middle-income countries including Brazil, where it was the mainstay of the first wave of immunization of ...healthcare workers and the elderly population. We aimed to assess the T cell and antibody responses of vaccinated individuals as compared to convalescent patients. We detected IgG against SARS-CoV-2 antigens, neutralizing antibodies against the reference Wuhan SARS-CoV-2 strain and used SARS-CoV-2 peptides to detect IFN-g and IL-2 specific T cell responses in a group of CoronaVac vaccinated individuals (N = 101) and convalescent (N = 72) individuals. The frequency among vaccinated individuals, of whom 96% displayed T cell and/or antibody responses to SARS-CoV-2, is comparable to 98.5% responses of convalescent individuals. We observed that among vaccinated individuals, men and individuals 55 years or older developed significantly lower anti-RBD, anti-NP and neutralization titers against the Wuhan strain and antigen-induced IL-2 production by T cells. Neutralizing antibody responses for Gamma variant were even lower than for the Wuhan strain. Even though some studies indicated CoronaVac helped reduce mortality among elderly people, considering the appearance of novel variants of concern, CoronaVac vaccinated individuals above 55 years old are likely to benefit from a heterologous third dose/booster vaccine to increase immune response and likely protection.
Platelet-rich plasma (PRP) has the potential to regenerate tissues and decrease pain through the effects of bioactive molecules and growth factors present in alpha granules. Several PRP preparation ...systems are available with varying end products, doses of growth factors, and bioactive molecules. This article presents the biology of PRP, the preparation of PRP, and the effects PRP-related growth factors have on tissue healing and repair. Based on available evidence-based literature, the success of PRP therapy depends on the method of preparation and composition of PRP, the patient's medical condition, anatomic location of the injection, and the type of tissue injected.
Corticosteroids have played a standard role in the multimodal pain management in the treatment of chronic spinal pain (cervical and lumbar) and osteoarthritis pain over the past three decades. In ...this review we discuss different types of injectable steroids that are mainly used for injection into the epidural space (for the treatment of radicular back and neck pain), and as intra-articular injections for different types of osteoarthritis related pain conditions. Furthermore, we discuss different approaches taken for epidural corticosteroid injections and spinal surgical rates when injections fail to resolve painful conditions, as well as the possibility of using local anesthetics alone for neuraxial injections, instead of in combination with corticosteroids. While we present some beneficial effects of newly available treatment options for low back pain and osteoarthritis pain, such as use of PRP and hyaluronic acid, corticosteroids remain important considerations in the management of these chronic pain conditions.
Acetaminophen, nonsteroidal antiinflammatory drugs (NSAIDs), and corticosteroids, historically used in perioperative management, are potent analgesic medications. They primarily inhibit the ...cyclooxygenase (COX) enzyme, decreasing the synthesis of prostaglandins, and modulating pain and temperature. Acetaminophen does not inhibit this synthesis at the inflammatory site. The primary mechanism of action of corticosteroids involves regulation of nuclear expression of genes involved in inflammatory pathways and other systemic effects. Metaanalyses have added purposeful perioperative indications, clarified misconceptions, and established protocols for administering these drugs. Some indications, doses, clinical considerations, and adverse effects need to be further studied.
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