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Pain management in both outpatient and inpatient settings demands a multidisciplinary approach entailing medical, physical and psychological therapies. Among these, multimodal analgesic regimens stand out as a promising treatment options. Cyclo-oxygenase (COX) inhibitor/opioid receptor agonist combinations hold great potential as effective pillars in the multimodal pain management by providing adequate analgesia with fewer safety risks due to COX inhibitors' opioid-sparing effect. Thus, these combinations, either freely or in fixed-dose formulation, offer a feasible option for the prescribing clinicians who seek to maximise therapeutic effect while simultaneously minimise adverse effects. The selection of the appropriate non-steroidal anti-inflammatory drug (NSAID) and opioid agent at optimal doses is essential. It should be tailored to the patients' analgesic necessities, and his/her gastrointestinal and cardiovascular risk, and potential concurrent aspirin use. Moreover, it should allow for addiction risk and the potential opioid-induced bowel dysfunction and constipation. To ensure an optimal match between the characteristics of the patient and the properties of the chosen medication, and to guide adequate and well-tolerated treatment decisions, it is of paramount importance to expand clinicians' knowledge of the currently available COX inhibitor/opioid receptor agonist combinations. This invited narrative review deals with the literature evidence covering the components of multimodal opioid-sparing analgesic regimens. Also, it provides insights into the clinically relevant choice criteria to ensure a patient-tailored analgesia.

Ibuprofen first came to market about 50 years ago and rapidly moved to over-the-counter (OTC) sales. In April 2019, the National Agency for the Safety of Medicines and Health Products (ANSM) of France issued a warning for NSAID uses by patients with infectious diseases based on an analysis of 20 years of real-world safety data on ibuprofen and ketoprofen. Nevertheless, ibuprofen remains a mainstay in the analgesic armamentarium and with numerous randomized clinical trials, head-to-head studies, and decades of clinical experience. The authors offer a review of the safety of ibuprofen and how it may differ from other NSAIDs. Ibuprofen is associated with certain well-known gastrointestinal adverse effects that are related to dose and patient population. Among nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen has a comparatively low risk of cardiovascular adverse effects. It has been associated with renal and hepatic adverse effects, which appear to depend on dose, concomitant medications, and patient population. The association of ibuprofen with infections is more complex in that it confers risk in some situations but benefits in others, the latter in cystic fibrosis. Emerging interest in the literature is providing evidence of the role of ibuprofen as a possible endocrine disrupter as well as its potential antiproliferative effects for cancer cells. Taken altogether, ibuprofen has a favorable safety profile and is an effective analgesic for many acute and chronic pain conditions, although it-like other NSAIDs-is not without risk. After 50 years, evidence is still emerging about ibuprofen and its unique safety profile among NSAIDs. FUNDING: The Rapid Service Fee was funded by Abbott Established Pharmaceuticals Division (EPD).

Dementia is an irreversible, progressive form of cognitive dysfunction that can affect memory, learning ability, thinking, orientation, comprehension, calculation, linguistic skills and executive function but which does not impair consciousness. Pain prevalence is high among the elderly who are also at elevated risk for dementia. Pain control for dementia patients is important but can be challenging for clinicians as cognitive deficits can make it difficult to identify, localize and assess pain. Cerebral changes associated with dementia may change how people process and experience pain in ways that are not entirely elucidated. Agitation is a frequent symptom of dementia and may be associated with untreated pain as agitation and aggression symptoms decrease when pain is effectively addressed.

Objective: The clinical management of inflammatory pain requires an optimal balance between effective analgesia and associated safety risks. To date, mechanisms associated with inflammatory pain are not completely understood because of their complex nature and the involvement of both peripheral and central mechanisms. This Expert Consensus document is intended to update clinicians about evolving areas of clinical practice and/or available treatment options for the management of patients with inflammatory pain., Method: An international group of experts in pain management covering the pharmacology, neurology and rheumatology fields carried out an independent qualitative systematic literature search using MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials., Results: Existing guidelines for pain management provide recommendations that do not satisfactorily address the complex nature of pain. To achieve optimal outcomes, drug choices should be individualized to guarantee the best match between the characteristics of the patient and the properties of the medication. NSAIDs represent an important prescribing choice in the management of inflammatory pain, and the recent results on paracetamol question its appropriate use in clinical practice, raising the need for re-evaluation of the recommendations in the clinical practice guidelines., Conclusions: Increasing clinicians' knowledge of the available pharmacologic options to treat different pain mechanisms offers the potential for safe, individualized treatment decisions. We hope that it will help implement the needed changes in the management of inflammatory pain by providing the best strategies and new insights to achieve the ultimate goal of managing the disease and obtaining optimal benefits for patients., Funding: Dompé Farmaceutici SPA and Paolo Procacci Foundation.

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?

Opioids affect the central nervous system and are known to produce dizziness, sleepiness, mood changes, and other actions that in some people have a negative impact on psychomotor or mental performance. The negative effects can be exacerbated in persons who are taking other prescription medications or illegal substances. Opioid-abusing drivers clearly represent an unnecessary danger to the public; although the vast majority of patients taking prescription opioids for pain safely drive to work and other activities, a subset may be impaired, but not be aware of or recognize the problem. The majority of pain patients would likely be surprised to learn that the legal systems in most parts of the world, including most states in the United States, do not differentiate between a pain patient taking a prescribed opioid at the right dose and frequency, and an abuser taking an illegal drug. For example, in some parts of the United States, a driver may be initially stopped for a relatively minor offense and, if the officer notices that the driver is wearing a fentanyl patch, charged with driving under the influence of drugs (DUID). The present narrative review attempts to highlight the existing problem, the different legal thresholds for arrest and prosecution for DUID, and the challenge of trying to have zero-tolerance for driving under the influence of a drug used illegally, while at the same time not arresting legitimate patients who are taking pain medication as prescribed. There is a clear and present need for an integrated assessment and addressing of the current confounding situation.

Introduction: The recent dramatic increase in intentional and unintentional deaths attributed to opioids has refocused attention on the therapeutic ratio (risk-benefit ratio) of opioid analgesics. Almost all traditional opioid analgesics produce their effects (therapeutic and adverse) via the activation of μ-opioid receptor (MOR) pathways. It is therefore important to examine the question of whether this natural endogenous pathway can still be activated, but with greater safety. Areas covered: Other comprehensive reviews have focused on pharmacokinetic (e.g. peripheral restriction) and pharmacodynamic (e.g. functional selectivity, biased ligand) approaches. Herein, the authors focus on a different approach, specifically, multi-mechanistic 'atypical opioids' that synergistically combines MOR activation plus one or more non-opioid mechanism of analgesic action. Expert opinion: Four 'atypical opioid' analgesics on the market act as μ-opioid receptor pathway agonists but have a non-opioid mechanism of action that significantly contributes to the analgesic effect. The multi-mechanistic action of these products confers particular clinical utility in that they provide effective analgesia with relatively lower opioid load, and they are generally associated with fewer or less severe opioid-related adverse effects and less abuse compared to traditional opioid analgesics.

Opioids remain the standard of care for treating moderate to severe pain resulting from surgery or injury in cases of acute pain, and are recommended for patients who have not responded to nonopioid analgesics. Effective management of pain has an impact on clinical course and often depends on achieving an acceptable balance between opioid efficacy, safety, and tolerability. Common opioid-related adverse events such as nausea and vomiting are associated with an overall lower achievement of effective pain management and patient satisfaction. However, in practice, clinicians employ various strategies to maximize efficacy, minimize these adverse effects, and ensure the careful, judicious, and evidence-based use of opioids for patients who require them. Typical strategies for management and minimization of these types of adverse events include dose reduction, dose titration, opioid rotation, prescription for an antiemetic, and recommending the patient take opioids with food. Overall, the most straightforward approach that clinicians tend to employ that does not require additional visits or adjustment of prescriptions, is to recommend patients take opioids with food. However, given the current climate with opioids, it is critical and imperative that decisions for use of opioids be grounded in a solid and thorough evidence-base. In fact, several opioids are recommended to be taken explicitly with or without food because of interactions with abuse-deterrent technologies that can cause increased adverse events or inadequate analgesia. Therefore, we sought to review, synthesize, and summarize the literature for randomized, controlled trials and other studies to support the hypothesis that taking opioids with food reduces opioid-related events such as nausea and vomiting. Based on the current evidence we surveyed, the recommendation to take opioids with food does not appear to consistently and unequivocally reduce nausea and vomiting and, in many cases, increases the frequency of these adverse events in the studies we examined.

All NSAIDs are to varying degrees associated with gastrointestinal, cardiovascular and renal adverse effects (AEs). Differences in selectivity for inhibition of the COX isozymes (COX-1/COX-2) have been used as an indicator of the likelihood of experiencing an AE, but the measure of 'selectivity' commonly used is less than desirable, and selectivity has not yielded unequivocal superior safety. Recent guidelines recommend that NSAIDs be used at the lowest effective dose and for the shortest period of time. In response, 'low-dose' NSAID formulations have been developed. Such formulations may help by reducing overall systemic exposure, thereby reducing the frequency or severity of AEs. It seems timely to review the need, rationale and application of such an approach.

The modern approach to the management of pain involves optimizing all aspects of the process. This includes utilization of pharmacologic and non-pharmacologic modalities, consideration of patient characteristics, proper matching of the physiology of the pain with the analgesic's mechanism of action (pharmacodynamics, PD), and the onset and duration of action (pharmacokinetics, PK). No single agent or formulation satisfies all of the requirements for all patients. Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are effective options for inflammatory pain and, as is acetaminophen, for mild pain. Specialized agents are helpful for particular pains, such as for migraine headache. Opioids remain the standard option for severe pain. Although they are generally a safe and effective option, opioids can produce dose-limiting adverse effects and have abuse potential. The goal of pain therapy is thus to achieve the maximum pain relief with the least amount of opioid exposure. Against this background of measured approach to the use of analgesics, an immediate release (IR) oral formulation of the established opioid oxycodone has been developed to provide rapid onset of action and rate of titration, both of which could maximize temporal matching of dose with pain level and reduce total exposure to drug. This article considers the option of an immediate release (IR) oral formulation for the management of pain.

Obesity and pain are common problems affecting the older adult and a possible relationship between the two is considered. Obesity and pain themselves are significant burdens on the individual, the healthcare system, and society as a whole and they can lead to emotional conditions such as stress, anxiety, and depression - which lead to further healthcare utilization and burden. Cross-sectional studies have revealed a high correlation between pain and obesity and a few longitudinal studies implicate obesity as a risk factor for the development of pain and the associated reduction in quality of life. Obesity leads to pain due to mechanical stress and metabolic disruptions, so mitigating obesity may help reduce the risk of developing pain and improve recovery from pain. More research is warranted to elucidate the mechanistic links between obesity and pain and to determine the optimal treatment strategies for reducing these comorbities. Reducing obesity could reduce pain medication burden.

There is a curious and paradoxic phenomenon, reliably demonstrated in animal models, that consists of an increased sensitivity to pain that is apparently induced by the very opioid drugs used to ameliorate the pain. This phenomenon is termed "opioid-induced hyperalgesia." Whether opioid-induced hyperalgesia occurs in humans, and, if so, to what extent and consequence, is far less established. This is a critical question for attempting to treat pain. If opioid-induced hyperalgesia develops in a patient, it would masquerade as tolerance (because the clinical effectiveness of the opioid would be diminished), yet the appropriate clinical adjustment would be precisely the opposite to that of tolerance. It would be to decrease, rather than increase, the dose of opioid. We review the evidence, particularly the clinical evidence, about opioid-induced hyperalgesia and the postulated mechanisms. We conclude that given the clinical ramifications, opioid-induced hyperalgesia is one of the most understudied important aspects of opioid research., (Copyright © 2013 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.)

Introduction: Opioid receptor antagonists are well known for their ability to attenuate or reverse the effects of opioid agonists. This property has made them useful in mitigating opioid side effects, overdose and abuse. Paradoxically, opioid antagonists have been reported to produce analgesia or enhance analgesia of opioid agonists. The authors review the current state of the clinical use of opioid antagonists as analgesics., Areas Covered: Published clinical trials, case reports and other sources were reviewed to determine the effectiveness and safety of opioid antagonists for use in relieving pain. The results are summarized. Postulated mechanisms for how opioid antagonists might exert an analgesic effect are also briefly summarized., Expert Opinion: Since the comprehensive review by Leavitt in 2009, few new studies on the use of opioid antagonists for pain have been published. The few clinical trials generally consist of small populations. However, there does appear to be a trend of effectiveness of low doses (higher doses antagonize opioid agonist effects). How opioid antagonists can elicit an analgesic effect is still unclear, but a number of possibilities have been suggested. Although the data do not yet support recommendation of widespread application of this off-label use of opioid antagonists, further study appears worthwhile.

Introduction: Pain is a large and growing medical need that is not currently being fully met, primarily due to the shortcomings of existing analgesics (insufficient efficacy or limiting side-effects). Better outcomes might be achieved using a combination of analgesics. The ratio of the combinations matters and should therefore be evaluated using rigorous quantitative and well-documented analysis., Areas Covered: Advances have been made in understanding the normal physiology of pain processing, including the pathways and neurotransmitters involved. Insight has also been gained about physiological processes that can lead to different 'types' of pain and the transition from acute to chronic pain conditions. This 'multimechanistic' nature of most pains is better matched using a 'multimechanistic' rather than 'monomechanistic' analgesic approach. Such an approach - and the experimental design and data analysis to assess optimal combinations - is described and discussed., Expert Opinion: There are sound pharmacologic, as well as practical, reasons for using combinations of drugs to treat pain. Compared with single agents, they offer a potential better match to the underlying pain physiology and thus greater efficacy or reduced side effects. The optimal efficacy and side-effect ratio must be determined in a scientifically rigorous manner.

Introduction: Tramadol is a centrally acting analgesic available throughout the world. Its dual opioid and non-opioid mechanisms of action, favorable efficacy and safety clinical profiles and non-controlled regulatory status in most markets contribute to its widespread use. A drawback of the immediate-release formulation of tramadol (four-times-a-day dosing) might be addressed by an extended-release formulation. Extended-release formulations also can offer advantages in the management of chronic pain: convenience, reduced pill burden (possibly leading to improved compliance) and the attenuation of peaks and troughs in serum concentration (possibly leading to reduced adverse effects)., Areas Covered: The authors review tramadol's mechanisms of action and the clinical literature regarding the use of tramadol extended-release formulations for the management of conditions involving chronic pain, such as neuropathic pain syndromes, osteoarthritis and cancer pain., Expert Opinion: Based on the literature cited, extended-release formulations of tramadol seem to offer a rational and important addition to the analgesic armamentarium. As is true for all such options, the benefits and risks must be assessed for each patient.

Physicians who prescribe opioid analgesics for patients with moderate to severe chronic pain face a balancing act in the wake of the current publicity regarding abuse (nonmedical use) of prescription pain killers. There is a spectrum of opioid abuse ranging from those who misuse the drug by not following doctor's orders to those who take the drugs to achieve a high or divert the drugs to the street market for profit. Formulations of opioid analgesics designed to resist or deter abuse have been proposed, and are now either on the market or in the pipeline. These are innovative formulations that make the drug less convenient or less desirable to abusers. This article examines three such new products along with clinical studies that report on their safety and effectiveness. These drugs include extended-release morphine with sequestered naloxone (Embeda), controlled-release oxycodone in a high-viscosity hard gelatin capsule (Remoxy) and an immediate-release oxycodone tablet with subtherapeutic niacin as an aversive agent (Acurox with niacin tablets). Extended-release morphine with sequestered naltrexone offers a pharmacological barrier in that pellets of morphine surround an internal core of naltrexone (ratio 100 : 4 of morphine : naltrexone), which is released if the tablet is compromised by chewing or crushing. The hard gelatin capsule of controlled-release oxycodone was designed to resist tampering and the drug cannot be extracted with a needle. The immediate-release oxycodone formulation with subtherapeutic niacin uses a gel-forming ingredient designed to inhibit inhalation and prevent extraction of the drug for injection. The subtherapeutic niacin is intended to induce flushing and other unpleasant effects if the drug is taken in an excessive quantity. While these drugs hold individual promise, it remains undetermined if they can truly prevent abuse. Drug-seeking individuals are extremely resourceful and show little loyalty to a particular drug when other drugs are available. It is possible that abuse-deterring formulations may divert such individuals to find other drugs that are easier to compromise. Nevertheless, these formulations are important innovations and warrant further study to assess their appropriate role as analgesics.

Unlabelled: When the pathophysiology of a medical condition is multimodal, ie, related to multiple physiological causes or mediated by multiple pathways, the optimal strategy can be to use a drug or a combination of drugs that contribute multiple mechanisms to the therapeutic endpoint. In such situations, a rational multimodal approach can also result in the fewest adverse effects. We discuss the quantitative analysis of multimodal action using the treatment of pain as a practical example and give examples of its application to some widely used analgesic drugs., Perspective: This article reviews the medical relevance of the quantitative evaluation of drug combinations, using pain and combinations of analgesics as specific examples. Such measure can help clinicians who seek to maximize therapeutic effect while simultaneously minimizing adverse effects., (Copyright (c) 2010 American Pain Society. Published by Elsevier Inc. All rights reserved.)

Objective: Essential oxygen oil (OxyRub from CreoMed Inc., Naples, FL, U.S.A.) is a novel topical analgesic currently commercially available in Europe and now available in the U.S.A. It represents an important alternative to other treatments (nonsteroidal anti-inflammatory drugs, acetaminophen, menthol, camphor) for managing mild to moderate acute and chronic pain. Several clinical trials of this oil will be reviewed., Results: One large (n = 455) open-label trial found essential oxygen oil to be a safe and effective analgesic for a broad range of patients with acute and chronic pain. In that study, 80% of patients reported that their pain decreased by more than 75%. A double-blind placebo-controlled study (n = 50) found significant pain reduction for tendonitis in patients using essential oxygen oil. Another trial of essential oxygen oil vs. placebo (n = 50) with various pain diagnoses found that 98% of patients with various pain diagnoses reported "very good" pain relief in the oil group compared to 48% in the placebo group. Furthermore, a randomized controlled trial in 10 women to measure oxygen microcirculatory effect in the skin showed an increased microcirculatory effect with improved oxygenation (increased partial pressure of oxygen in the skin) after application of essential oxygen oil. In all studies, the oil was well tolerated. None of these studies has been previously published., Conclusions: Based on studies completed, essential oxygen oil has shown itself to be safe, has demonstrated positive analgesic effects for the treatment of acute and chronic pain, and has improved oxygen content in the skin as well as other dermatological parameters.

Background: Pain among the elderly is pervasive, under-treated and can be properly managed by judiciously using analgesics in the armamentarium. For severe pain, opioids generally provide the most effective pain relief, but concerns about safety and tolerability have limited, often unnecessarily, their utilization in the geriatric population., Objective: It is common for geriatric patients to be taking more than one medicine. Oxymorphone might be particularly well suited for use in geriatric patients, in that its metabolism is mainly through non-CYPP450 pathways, thereby posing less risk of interaction with the many drugs that are metabolized by the CYPP450 system. However, oxymorphone is not as familiar to clinicians as morphine or some other opioids. We review here the clinical studies on oxymorphone to outline the key considerations for use of oxymorphone in the geriatric population., Methods: Nine available clinical trials of oxymorphone alone or comparing oxymorphone with placebo or other active agents were analyzed with respect to the safety and tolerability findings. These studies included geriatric patients but were not designed to evaluate oxymorphone exclusively in this population., Results: Based on the results from nine published clinical studies, oxymorphone is an effective opioid analgesic with a safety profile at least comparable to other opioid drugs. At low starting doses and individual titration, oxymorphone should be considered for appropriate geriatric patients, particularly in whom there is concern about interaction with drugs that are metabolized by CYPP450 enzymes.

Background: The semi-synthetic opioid, buprenorphine, has the general structure of morphine but differs from it in significant ways, both pharmacologically and clinically. A number of long-term studies have shown effective, long-lasting analgesia in moderate to severe cancer and non-cancer pain, including neuropathic pain, with a low incidence of constipation, nausea, dizziness and tiredness. The treatment of moderate to severe chronic pain has improved as a result of the development of new methods of administration of this substance, particularly the introduction of the transdermal drug delivery system, which offers a number of advantages over the usual oral and parenteral routes., Scope: A panel of experts specialising in palliative care and pain treatment was convened in November 2007 to discuss their clinical experiences with transdermal buprenorphine and other analgesics. The aim was to provide practical guidance on the treatment of cancer pain with transdermal buprenorphine, particularly when there is a need for increasing pain relief leading to high and increasing doses. A literature search on the use of transdermal buprenorphine was carried out for the panel meeting (based on a search of PubMed to November 2007 - since updated by an additional search for the period to February 2009) and a number of case histories were presented and discussed. This commentary article presents this evidence and the consensus findings of the expert panel., Findings: The Panel reached consensus that transdermal buprenorphine was a valuable treatment for chronic cancer pain, including its neuropathic components. A number of general recommendations were made. Large-scale, randomised clinical studies are needed to provide product comparisons on the use of analgesics in the treatment of neuropathic pain although it was recognised that such studies may not be practicable. Data on the treatment of acute and chronic pain should be kept separate in general. Physicians should be made more aware of the problem of hyperalgesic effects of some opioids in long term use. Buprenorphine in contrast has been described to exert an antihyperalgesic effect. The development of analgesic tolerance with some opioids in long term use and the lack of it with buprenorphine requires further studies. The registered dose range of 35-140 microg/h was considered adequate to achieve sufficient pain relief in most patients although some members of the panel presented data showing that increases beyond this dose range provided improved pain relief if slow titration is used. However, it was generally felt that more evidence was needed before this could become generally acceptable., Conclusion: The consensus was that transdermal buprenorphine has a valuable role to play in the treatment of chronic cancer pain because of its efficacy and good safety and tolerability profile, including a low risk of respiratory depression, a lack of immunosuppression and a lack of accumulation in patients with impaired renal function.

Background: Despite the high prevalence of neck pain, few studies have addressed the pharmacological treatment of this condition.Purpose: We evaluated the effectiveness of tapentadol prolonged-release (PR) in patients with or without a neuropathic pain component, with a focus on functional movements, disability and Quality of Life (QoL).Study design/setting: Observational, retrospective study.Patient sample: Ninety-four adult patients with severe neck pain not responsive to opioid step III treatment.Outcome measures: The primary endpoint was a ≥ 30% improvement of pain intensity at 4 weeks (W4). Several secondary outcomes were evaluated, including neck disability index (NDI), range of motion (ROM), and QoL.Methods: Patients received tapentadol PR at the starting dose of 100 mg/day. Dose titration was allowed in 50 mg increments, up to 500 mg daily.Results: At W4, the primary endpoint of ≥30% improvement of pain was reported in 70% (n = 35; 95% confidence interval [CI]: 55-82%) of patients with a neuropathic pain component and in 69% (n = 20; 95% CI: 49-85%) of those without a neuropathic component. The percentage of patients reporting a neuropathic pain component significantly decreased from baseline (64.2%) to W4 (27.8%). NDI significantly improved in both groups at W12. ROM significantly improved in all three planes of motion (p < .01), with no difference between the two groups. Interference of pain with sleep and QoL also improved.Conclusions: The reduction in pain provided by tapentadol is associated with functional recovery, which may in turn be linked to an improvement in QoL. [ABSTRACT FROM AUTHOR]

The frequently prescribed drug class of statins have pleiotropic effects and have been implicated in neuropathic pain syndromes. This narrative review examines studies of statin-induced neuropathic pain which to date have been conducted only in animal models. However, the pathophysiology of diabetic neuropathy in humans may shed some light on the etiology of neuropathic pain. Statins have exhibited a paradoxical effect in that statins appear to reduce neuropathic pain in animals but have been associated with neuropathic pain in humans. While there are certain postulated mechanisms offering elucidation as to how statins might be associated with neuropathic pain, there is, as the American Heart Association stated, to date no definitive association between statins and neuropathic pain. Statins are important drugs that reduce cardiovascular risk factors and should be prescribed to appropriate patients with these risk factors but some of this population is also at elevated risk for neuropathic pain from other causes. [ABSTRACT FROM AUTHOR]

Summary: What is known and objective: When patients fail other treatment regimens and still suffer from pain sufficiently severe, opioid analgesics are appropriate and required. Unfortunately, constipation is a common adverse effect of opioids. Opioid‐induced constipation (OIC) can be treated with one of the new peripherally acting µ‐opioid receptor antagonist (PAMORA) agents. We summarize the mechanism of action of these drugs, with an emphasis on comparison of their potential for metabolic drug interactions. Methods: Internet sources were searched for English‐language abstracts related to the topic. Emphasis was placed on the mechanism of the PAMORAs, their metabolic pathways, drugs co‐administered with opioids and potential drug‐drug interactions (particularly at the level of CYP450 isozyme drug metabolism). Each source was evaluated and synthesized into the review. Results and discussion: PAMORAs dose‐dependently antagonize the access of agonist molecules to opioid receptors, thereby directly eliminating or reducing OIC. But they differ from other opioid antagonists in that they are restricted to the periphery. Hence, they block constipation, but leave central opioid receptor‐mediated pain relief undiminished. The PAMORAs have similar efficacy and safety profiles, but many pain patients have comorbidities and thus are taking other medications, which increases the potential for metabolic drug interactions. What is new and conclusion: Managing OIC in patients who have failed OTC or other therapies can be accomplished using a PAMORA, but healthcare providers must make prudent decisions that avoid or at least mitigate the potential for metabolic drug interactions in those patients with other comorbidities being managed medically by rational polypharmacy strategies. [ABSTRACT FROM AUTHOR]

Intravenous ( IV) analgesia has particular advantages in the immediate postoperative period. For example, IV administration results in a faster onset of pain relief and results in more predictable pharmacokinetics than does administration by other routes. It also allows for convenient dosing before or during surgery, permitting the initiation of effective analgesia in the early phase of the postoperative period. In addition, when patients are able to tolerate oral intake, they can be switched from IV to oral dosing based on maintaining the predictable analgesia established by the IV route. IV morphine is widely used for the control of postoperative pain, but there is a trend toward the use of oxycodone. Oxycodone (which may be mediated partly through kappa- as well as mu-opioid receptors) offers several potential advantages. Published studies comparing IV oxycodone to other IV opioids for postsurgical pain report that oxycodone is a safe and effective analgesic. Some studies show that IV oxycodone may be associated with greater pain control, fewer or less severe adverse events, and faster onset of action, although the results are not consistent across all studies. Oxycodone has been reported to be safe in the geriatric and other special populations when adequate clinical adjustments are made. Thus, the clinical reports and oxycodone's pharmacologic profile make intravenous oxycodone a potentially important 'new' old drug for postoperative pain control. [ABSTRACT FROM AUTHOR]

Objective To evaluate the impact of buprenorphine ( Butrans®) transdermal System ( BTDS) treatment on sleep outcomes for patients with moderate-to-severe chronic low back pain ( CLBP). Methods Two enriched-enrollment, randomized-withdrawal, double-blind, controlled trials examined BTDS treatment for patients with moderate-to-severe CLBP. Trial I evaluated BTDS 10 and 20 mcg/hour against a placebo control among opioid-naïve patients. Trial II compared BTDS 20 mcg/hour against a lower-dose control ( BTDS 5 mcg/hour) among opioid-experienced patients. The patient-reported Medical Outcomes Study Sleep Scale ( MOS- SS) assessed overall sleep quality ( Sleep Problems Index [ SPI]), Disturbance, and other sleep outcomes. In each trial, MOS- SS scores were compared between target treatment and control arms during the 12-week double-blind phase. Correspondence of changes in sleep outcomes and pain severity and the degree to which pain reduction mediates treatment impact on sleep outcomes were examined. Results Medical Outcomes Study Sleep Scale scores were collected from 541 ( Trial I) and 441 ( Trial II) patients prior to randomization and from 369 ( Trial I) and 274 ( Trial II) patients at week 12. Patients receiving target treatment showed statistically significantly more improvement in SPI and Disturbance scores at 12 weeks than their respective controls ( Ps < 0.05). Improvements in SPI and Disturbance for target treatment arms were statistically larger those of the controls by week 4 of the double-blind phase. The clinical significance of these differences was not determined. Pain reduction predicted improvements in sleep outcomes. Conclusion Buprenorphine Transdermal System improved sleep quality and disturbance for opioid-naïve and opioid-experienced patients with moderate-to-severe CLBP. Benefits of BTDS for these sleep outcomes emerged within 4 weeks and were maintained over the entire 12-week treatment period. [ABSTRACT FROM AUTHOR]

Cancer pain is prevalent, undertreated, and feared by patients with cancer. In April 2013, a panel of pain experts convened in Singapore to address the treatment of cancer pain. They discussed the various types of cancer pain, including breakthrough pain, which is sometimes clinically confused with analgesic gaps. Reasons for undertreating cancer pain include attitudes of patients, clinicians, and factors associated with healthcare systems. The consequences of not treating cancer pain may include reduced quality of life for patients with cancer (who now live longer than ever), functional decline, and increased psychological stress. Early analgesic intervention for cancer pain may reduce the risk of central sensitization and chronification of pain. To manage pain in oncology patients, clinicians should assess pain during regular follow-up visits using validated pain measurement tools and follow prescribing guidelines, if necessary referring patients with cancer to pain specialists. Many patients with cancer require opioids for pain relief. Pain associated with cancer may also relate to cancer treatments, such as chemotherapy-induced peripheral neuropathy. Many patients with cancer are what might be considered 'special populations,' in that they may be elderly, frail, comorbid, or have end-stage organ failure. Specific pain therapy guidelines for those populations are reviewed. Patients with cancer with a history of or active substance abuse disorder deserve pain control but may require close medical supervision. While much 'treatment inertia' exists in cancer pain control, cancer pain can be safely and effectively managed and should be carried out to alleviate suffering and improve outcomes. [ABSTRACT FROM AUTHOR]

Despite recent advances in the knowledge of pain mechanisms and pain management, postoperative pain continues to be a problem. Inadequately managed postsurgical pain has both clinical and economic consequences such as longer recovery times, delayed ambulation, higher incidence of complications, increased length of hospital stay, and potential to develop into chronic pain. Generally, opioids are the mainstay option for pain management in patients with moderate-to-severe postsurgical pain; however, opioids have significant side effects and have abuse potential. To improve patient and economic outcomes after surgery, postoperative pain guidelines have suggested incorporating a multi-modal/multi-mechanistic approach to pain treatment. A multi-modal approach is the simultaneous use of a combination of two or more (usually opioid and non-opioid) analgesics that provide two different mechanisms of actions. Utilizing a multi-modal approach may result in a greater reduction in pain vs. single therapies in addition to minimizing opioid use, thus reducing opioid related side effects. However, not all approaches may be effective for all types of patients and not all analgesics may be a viable option for outpatient settings, ambulatory surgery, or the fast-track surgical procedures. In this report, we present a review of the literature with a focus on intranasal ketorolac in order to provide a timely update regarding past, present, and future multi-modal treatment options for postoperative pain. [ABSTRACT FROM AUTHOR]

Poorly controlled acute pain during the postoperative setting after abdominal surgery can be detrimental to the patient. Current pain management practices for the postoperative abdominal surgery patient rely heavily on opioids, which are associated with many unwanted side effects. Recently, interest surrounding regional anesthesia has been growing owing to its demonstrated efficacy and safety outcomes. More specifically, the transversus abdominis plane ( TAP) block procedure has attracted attention owing to its ability to successfully block peripheral pain signaling in the abdomen, its ease of use, few complications, and its greater acceptability. A majority of the studies published has demonstrated the successful reduction in pain in many abdominal surgical procedures using local anesthetics during the TAP block. However, the short duration of the pain block causes the patient to still rely on other analgesics throughout the additional postoperative days. Preliminary studies using continuous infusion catheters placed in the TAP has been one of the ways to prolong the nerve block in the abdomen; however, technical and operational issues currently limit the widespread adoption of this method. In this review, current studies will be presented and summarized to update the field on the potential benefits of the TAP block procedure, in addition to providing insight into the future direction of the drugs that could be used for TAP block. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to systematically review the literature to assess the efficacy of nonsurgical spinal decompression achieved with motorized traction for chronic discogenic lumbosacral back pain. Design: Computer-aided systematic literature search of MEDLINE and the Cochrane collaboration for prospective clinical trials on adults with low back pain in the English literature from 1975 to October 2005. Methodologic quality for each study was assessed. Studies were included if the intervention group received motorized spinal decompression and the comparison group received sham or another type of nonsurgical treatment. Results: Data from 10 studies were fully analyzed. Seven studies were randomized controlled trials using various apparatus types. Because of this low number, we also analyzed three nonrandomized case series studies of spinal decompression systems. As the overall quality of studies was low and the patient groups heterogeneous, a meta-analysis was not appropriate and a qualitative review was undertaken. Sample sizes averaged 121 patients (range 27–292), with six of the seven randomized studies reporting no difference with motorized spinal decompression and one study reporting reduced pain but not disability. The three unrandomized studies (no control group) of motorized spinal decompression found a 77% to 86% reduction in pain. Conclusions: These data suggest that the efficacy of spinal decompression achieved with motorized traction for chronic discogenic low back pain remains unproved. This may be, in part, due to heterogeneous patient groups and the difficulties involved in properly blinding patients to the mechanical pulling mechanism. Scientifically more rigorous studies with better randomization, control groups, and standardized outcome measures are needed to overcome the limitations of past studies. [ABSTRACT FROM AUTHOR]