Chronic pain is a public health concern affecting 20–30% of the population of Western countries. Although there have been many scientific advances in the understanding of the neurophysiology of pain, ...precisely assessing and diagnosing a patient's chronic pain problem is not straightforward or well-defined. How chronic pain is conceptualized influences how pain is evaluated and the factors considered when making a chronic pain diagnosis. There is no one-to-one relationship between the amount or type of organic pathology and pain intensity, but instead, the chronic pain experience is shaped by a myriad of biomedical, psychosocial (e.g. patients’ beliefs, expectations, and mood), and behavioural factors (e.g. context, responses by significant others). Assessing each of these three domains through a comprehensive evaluation of the person with chronic pain is essential for treatment decisions and to facilitate optimal outcomes. This evaluation should include a thorough patient history and medical evaluation and a brief screening interview where the patient's behaviour can be observed. Further assessment to address questions identified during the initial evaluation will guide decisions as to what additional assessments, if any, may be appropriate. Standardized self-reported instruments to evaluate the patient's pain intensity, functional abilities, beliefs and expectations, and emotional distress are available, and can be administered by the physician, or a referral for in depth evaluation can be made to assist in treatment planning.
Neuropathic pain (NP) is often refractory to pharmacologic and noninterventional treatment. On behalf of the International Association for the Study of Pain Neuropathic Pain Special Interest Group, ...the authors evaluated systematic reviews, clinical trials, and existing guidelines for the interventional management of NP. Evidence is summarized and presented for neural blockade, spinal cord stimulation (SCS), intrathecal medication, and neurosurgical interventions in patients with the following peripheral and central NP conditions: herpes zoster and postherpetic neuralgia (PHN); painful diabetic and other peripheral neuropathies; spinal cord injury NP; central poststroke pain; radiculopathy and failed back surgery syndrome (FBSS); complex regional pain syndrome (CRPS); and trigeminal neuralgia and neuropathy. Due to the paucity of high-quality clinical trials, no strong recommendations can be made. Four weak recommendations based on the amount and consistency of evidence, including degree of efficacy and safety, are: 1) epidural injections for herpes zoster; 2) steroid injections for radiculopathy; 3) SCS for FBSS; and 4) SCS for CRPS type 1. Based on the available data, we recommend not to use sympathetic blocks for PHN nor radiofrequency lesions for radiculopathy. No other conclusive recommendations can be made due to the poor quality of available data. Whenever possible, these interventions should either be part of randomized clinical trials or documented in pain registries. Priorities for future research include randomized clinical trials, long-term studies, and head-to-head comparisons among different interventional and noninterventional treatments.
Irreversible covalent inhibitors can have a beneficial pharmacokinetic/pharmacodynamics profile but are still often avoided due to the risk of indiscriminate covalent reactivity and the resulting ...adverse effects. To overcome this potential liability, we introduced an alkyne moiety as a latent electrophile into small molecule inhibitors of cathepsin K (CatK). Alkyne-based inhibitors do not show indiscriminate thiol reactivity but potently inhibit CatK protease activity by formation of an irreversible covalent bond with the catalytic cysteine residue, confirmed by crystal structure analysis. The rate of covalent bond formation (k inact) does not correlate with electrophilicity of the alkyne moiety, indicative of a proximity-driven reactivity. Inhibition of CatK-mediated bone resorption is validated in human osteoclasts. Together, this work illustrates the potential of alkynes as latent electrophiles in small molecule inhibitors, enabling the development of irreversible covalent inhibitors with an improved safety profile.
OBJECTIVEChronic pain is a prevalent and costly problem. This review addresses the question of the clinical effectiveness and cost-effectiveness of the most common treatments for patients with ...chronic pain.
DATA SOURCESRepresentative published studies that evaluate the clinical effectiveness of pharmacological treatments, conservative (standard) care, surgery, spinal cord stimulators, implantable drug delivery systems (IDDSs), and pain rehabilitation programs (PRPs) are examined and compared. The cost-effectiveness of these treatment approaches is also considered.
DATA SYNTHESISOutcome criteria including pain reduction, medication use, health care consumption, functional activities, and closure of disability compensation cases are examined. In addition to clinical effectiveness, the cost-effectiveness of PRPs, conservative care, surgery, spinal cord stimulators, and IDDSs are compared using costs to return a treated patient to work to illustrate the relative expenses for each of these treatments.
CONCLUSIONSThere are limitations to the success of all the available treatments. The author urges caution in interpreting the results, particularly in comparisons between treatments and across studies, because there are broad differences in the pain syndromes and inclusion criteria used, the drug dosages, comparability of treatments, the definition of “chronic” used, the outcome criteria selected to determine success, and societal differences. None of the currently available treatments eliminates pain for the majority of patients. Pain rehabilitation programs provide comparable reduction in pain to alternative pain treatment modalities, but with significantly better outcomes for medication use, health care utilization, functional activities, return to work, closure of disability claims, and with substantially fewer iatrogenic consequences and adverse events. Surgery, spinal cord stimulators, and IDDSs appear to have substantial benefits on some outcome criteria for carefully selected patients. These modalities are, however, expensive. Pain rehabilitation programs are significantly more cost effective than implantation of spinal cord stimulators, IDDSs, conservative care, and surgery, even for selected patients. Research is needed to identify which patients are most likely to benefit from the available treatments and to study combinations of the available treatments since none of them appear capable of eliminating pain or significantly improving functional outcomes for all treated.
A large and diverse number of treatments have been shown to be effective in reducing pain and other symptoms for a minority but statistically significant number of patients in different chronic pain ...syndromes. The means by which such different treatments achieve similar outcomes is not well understood. In this paper, the importance of considering patient heterogeneity for those who may be diagnosed with the same medical syndrome is discussed. The author suggests that the lack of satisfactory treatment outcomes for the treatments of chronic pain syndromes may be accounted for by the patient homogeneity myth-the assumption that all patients with the same medical diagnosis are similar on all important variables. The importance of subdividing (splitting) patients into meaningful groups is described. Studies presenting data on the identification of patient subgroups based on psychosocial and behavioral characteristics and the reliability and validity of this approach are presented. Some initial attempts to demonstrate the potential for matching treatments to patient subgroups are described.
Treatment of chronic non-cancer pain Turk, Dennis C, Prof; Wilson, Hilary D, PhD; Cahana, Alex, Prof
The Lancet (British edition),
2011-Jun-25, Letnik:
377, Številka:
9784
Journal Article
Recenzirano
Chronic pain is a pervasive problem that affects the patient, their significant others, and society in many ways. The past decade has seen advances in our understanding of the mechanisms underlying ...pain and in the availability of technically advanced diagnostic procedures; however, the most notable therapeutic changes have not been the development of novel evidenced-based methods, but rather changing trends in applications and practices within the available clinical armamentarium. We provide a general overview of empirical evidence for the most commonly used interventions in the management of chronic non-cancer pain, including pharmacological, interventional, physical, psychological, rehabilitative, and alternative modalities. Overall, currently available treatments provide modest improvements in pain and minimum improvements in physical and emotional functioning. The quality of evidence is mediocre and has not improved substantially during the past decade. There is a crucial need for assessment of combination treatments, identification of indicators of treatment response, and assessment of the benefit of matching of treatments to patient characteristics.
Bothersome pain afflicts half of the community-dwelling US older adult population and is associated with significant reduction in physical function, particularly in those with multisite pain.
This ...study sought to determine the prevalence and impact of pain in a nationally representative sample of older adults in the United States. Data from the 2011 National Health and Aging Trends Study were analyzed. In-person interviews were conducted in 7601 adults ages ⩾65years. The response rate was 71.0% and all analyses were weighted to account for the sampling design. The overall prevalence of bothersome pain in the last month was 52.9%, afflicting 18.7 million older adults in the United States. Pain did not vary across age groups (P=0.21), and this pattern remained unchanged when accounting for cognitive performance, dementia, proxy responses, and residential care living status. Pain prevalence was higher in women and in older adults with obesity, musculoskeletal conditions, and depressive symptoms (P<0.001). The majority (74.9%) of older adults with pain endorsed multiple sites of pain. Several measures of physical capacity, including grip strength and lower-extremity physical performance, were associated with pain and multisite pain. For example, self-reported inability to walk 3 blocks was 72% higher in participants with than without pain (adjusted prevalence ratio 1.72 95% confidence interval 1.56–1.90). Participants with 1, 2, 3, and ⩾4 sites of pain had gait speeds that were 0.01, 0.03, 0.05, and 0.08 meters per second slower, respectively, than older adults without pain, adjusting for disease burden and other potential confounders (P<0.001). In summary, bothersome pain in the last month was reported by half of the older adult population of the United States in 2011 and was strongly associated with decreased physical function.
The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of ...neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel α2 -δ ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.
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