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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There has been a need for a brief assessment tool to determine compliance with use of prescribed opioids for pain. The purpose of this study was to develop and begin the validation of a brief and simple compliance checklist (Opioid Compliance Checklist [OCC]) for chronic pain patients prescribed long-term opioid therapy. A review of the literature of opioid therapy agreements led to a 12-item OCC that was repeatedly administered to 157 patients who were taking opioids for chronic pain and followed for 6 months. Validation of the OCC was conducted by identifying those patients exhibiting aberrant drug-related behavior as determined by any of the following: positive urine toxicology screen, a positive score on the Prescription Drug Use Questionnaire interview or Current Opioid Misuse Measure, and/or ratings by staff on the Addiction Behavior Checklist. Of the original 12 items, 5 OCC items appeared to best predict subsequent aberrant behaviors based on multivariate logistic regression analyses (cross-validated area under the receiver operating characteristic curve = .67). Although further testing is needed, these results suggest that the OCC is an easy-to-use, promising measure in monitoring opioid adherence among persons with chronic pain. ⋯ This study presents validation of a brief 5-item compliance checklist for use with chronic pain patients prescribed long-term opioid therapy. This measure asks patients about aberrant drug-related behavior over the past month, and any positive response indicates problems with adherence with opioids. Further cross-validation testing is needed.