The journal of pain : official journal of the American Pain Society
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Fentanyl, introduced more than 50 years ago, has become the most often used opioid for intraoperative analgesia. Since the early 1990s the fentanyl patch has been available for management of chronic pain of all forms of cancer as well as the persistent, intense pain from many noncancerous maladies. ⋯ The purpose of this article is to describe why this opioid has become so important in the treatment of pain in modern clinical practice. The data indicate that fentanyl's popularity has occurred because it has minimal cardiovascular effects, does not result in increases in plasma histamine, is relatively short in onset of action and duration of effect, is easy and inexpensive to synthesize and prepare for the marketplace, and is now familiar to clinicians working in pain and perioperative medicine throughout the world.
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Disorders of pain neural systems are frequently chronic and, when recalcitrant to treatment, can severely degrade the quality of life. The pain pathway begins with sensory neurons in dorsal root or trigeminal ganglia, and the neuronal subpopulations that express the transient receptor potential cation channel, subfamily V, member 1 (TRPV1) ion channel transduce sensations of painful heat and inflammation and play a fundamental role in clinical pain arising from cancer and arthritis. In the present study, we elucidate the complete transcriptomes of neurons from the TRPV1 lineage and a non-TRPV1 neuroglial population in sensory ganglia through the combined application of next-gen deep RNA-Seq, genetic neuronal labeling with fluorescence-activated cell sorting, or neuron-selective chemoablation. RNA-Seq accurately quantitates gene expression, a difficult parameter to determine with most other methods, especially for very low and very high expressed genes. Differentially expressed genes are present at every level of cellular function from the nucleus to the plasma membrane. We identified many ligand receptor pairs in the TRPV1 population, suggesting that autonomous presynaptic regulation may be a major regulatory mechanism in nociceptive neurons. The data define, in a quantitative, cell population-specific fashion, the molecular signature of a distinct and clinically important group of pain-sensing neurons and provide an overall framework for understanding the transcriptome of TRPV1 nociceptive neurons. ⋯ Next-gen RNA-Seq, combined with molecular genetics, provides a comprehensive and quantitative measurement of transcripts in TRPV1 lineage neurons and a contrasting transcriptome from non-TRPV1 neurons and cells. The transcriptome highlights previously unrecognized protein families, identifies multiple molecular circuits for excitatory or inhibitory autocrine and paracrine signaling, and suggests new combinatorial approaches to pain control.
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Neuropathic pain is a debilitating condition caused by a lesion or disease of the somatosensory nervous system. Statins inhibit the rate-limiting step in cholesterol biosynthesis by blocking 3-hydroxy-3-methyl glutaryl coenzyme A reductase. Apart from the cholesterol-reducing actions of statins, recent studies have shown their pleiotropic actions; accordingly, their usefulness in attenuating different disease states has been described in preclinical studies. Studies in animals have also suggested their beneficial effects in attenuating neuropathic pain in various animal models of neuropathy. In these studies, their usefulness has been ascribed to cholesterol-independent actions, including anti-inflammatory, antioxidant, and neuromodulatory effects. On the contrary, clinical evidence suggests that statin administration in patients is associated with development of neuropathy, suggesting the dichotomous role of statins in neuropathic pain. The present review discusses the pain-attenuating as well as pain-inducing role of statins in preclinical and clinical studies, respectively. Furthermore, the review provides mechanistic insight to explain the paradoxical nature of this class of drugs in neuropathy in preclinical and clinical studies. ⋯ The article reviews the pain-inducing role of statins in clinical studies and its neuropathic pain-attenuating role in preclinical studies with possible mechanisms. Understanding key differences in mechanisms may help to attenuate pain induction in the clinical setting and may possibly project statins as neuropathic pain-attenuating agents.
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Prior studies have demonstrated poor physician adherence to opioid management guidelines in primary care. The objectives of this qualitative study were to understand physicians' and patients' perspectives on recommended opioid management practices and to identify potential barriers to and facilitators of guideline-concordant opioid management in primary care. Individual semistructured interviews were conducted with 14 primary care physicians and 26 of their patients receiving long-term opioid therapy. Data were analyzed using a qualitative immersion/crystallization approach. We identified 3 major barriers to and 1 facilitator of use of recommended opioid management practices. Major barriers were inadequate time and resources available; relying on general impressions of risk for opioid misuse; and viewing opioid monitoring as a "law enforcement" activity. The third barrier was most apparent for physicians in the context of drug testing and for patients in the context of opioid agreements. Beliefs about the need to protect patients from opioid-related harm emerged as a major facilitator, especially among patients. We hypothesize that future interventions to improve opioid management in primary care will be more effective if they address identified barriers and use a patient-centered framework, in which prevention of opioid-related harm to patients is emphasized as the primary goal. ⋯ This article describes primary care perspectives on guideline-recommended opioid management practices. Barriers identified in this study may contribute to underuse of recommended opioid management practices. Consideration of barriers and facilitators to guideline-concordant care could improve effectiveness of future interventions aimed at improving opioid management in primary care.