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American Family Physician Jul 2021Pharmacologic management of acute pain should be tailored for each patient, including a review of treatment expectations and a plan for the time course of prescriptions.... (Review)
Review
Pharmacologic management of acute pain should be tailored for each patient, including a review of treatment expectations and a plan for the time course of prescriptions. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) are first-line treatment options for most patients with acute mild to moderate pain. Topical NSAIDs are recommended for non-low back, musculoskeletal injuries. Acetaminophen is well tolerated; however, lower doses should be used in patients with advanced hepatic disease, malnutrition, or severe alcohol use disorder. Nonselective NSAIDs are effective but should be used with caution in patients with a history of gastrointestinal bleeding, cardiovascular disease, or chronic renal disease. Selective cyclooxygenase-2 NSAIDs are a more expensive treatment alternative and are used to avoid the gastrointestinal adverse effects of nonselective NSAIDs. Adjunctive medications may be added as appropriate for specific conditions if the recommended dose and schedule of first-line agents are inadequate (e.g., muscle relaxants may be useful for acute low back pain). For severe or refractory acute pain, treatment can be briefly escalated with the use of medications that work on opioid and monoamine receptors (e.g., tramadol, tapentadol) or with the use of acetaminophen/opioid or NSAID/opioid combinations. The opioid epidemic has increased physician and community awareness of the harms of opioid medications; however, severe acute pain may necessitate short-term use of opioids with attention to minimizing risk, including in patients on medication-assisted therapy for opioid use disorder.
Topics: Acute Pain; Analgesics; Humans; Pain Management
PubMed: 34264611
DOI: No ID Found -
Pain Medicine (Malden, Mass.) Jun 2019The objective of this review was to merge current treatment guidelines and best practice recommendations for management of neuropathic pain into a comprehensive... (Review)
Review
BACKGROUND
The objective of this review was to merge current treatment guidelines and best practice recommendations for management of neuropathic pain into a comprehensive algorithm for primary physicians. The algorithm covers assessment, multidisciplinary conservative care, nonopioid pharmacological management, interventional therapies, neurostimulation, low-dose opioid treatment, and targeted drug delivery therapy.
METHODS
Available literature was identified through a search of the US National Library of Medicine's Medline database, PubMed.gov. References from identified published articles also were reviewed for relevant citations.
RESULTS
The algorithm provides a comprehensive treatment pathway from assessment to the provision of first- through sixth-line therapies for primary care physicians. Clear indicators for progression of therapy from firstline to sixth-line are provided. Multidisciplinary conservative care and nonopioid medications (tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, gabapentanoids, topicals, and transdermal substances) are recommended as firstline therapy; combination therapy (firstline medications) and tramadol and tapentadol are recommended as secondline; serotonin-specific reuptake inhibitors/anticonvulsants/NMDA antagonists and interventional therapies as third-line; neurostimulation as a fourth-line treatment; low-dose opioids (no greater than 90 morphine equivalent units) are fifth-line; and finally, targeted drug delivery is the last-line therapy for patients with refractory pain.
CONCLUSIONS
The presented treatment algorithm provides clear-cut tools for the assessment and treatment of neuropathic pain based on international guidelines, published data, and best practice recommendations. It defines the benefits and limitations of the current treatments at our disposal. Additionally, it provides an easy-to-follow visual guide of the recommended steps in the algorithm for primary care and family practitioners to utilize.
Topics: Algorithms; Humans; Neuralgia; Pain Management
PubMed: 31152178
DOI: 10.1093/pm/pnz075 -
Annals of Palliative Medicine Mar 2023Painful diabetic peripheral neuropathy (DPN) affects approximately 6-34% of all patients with diabetes. DPN-induced pain reduces the quality of life and makes daily... (Review)
Review
BACKGROUND AND OBJECTIVE
Painful diabetic peripheral neuropathy (DPN) affects approximately 6-34% of all patients with diabetes. DPN-induced pain reduces the quality of life and makes daily activities difficult. Distal symmetric polyneuropathy (DSPN) is the most common type of DPN. Here we review the pathophysiology, diagnosis, and treatment of DPN.
METHODS
A MEDLINE database (PubMed) search was conducted for English-language articles dealing with the effect of DPN that were published until April 1, 2022. To identify potentially relevant articles, the following key search phrases were combined: 'diabetes mellitus', 'diabetes', 'neuropathy', 'polyneuropathy', 'diabetic neuropathies', 'peripheral neuropathy', 'diabetic polyneuropathy', 'pathophysiology', 'diagnosis', and 'treatment'.
KEY CONTENT AND FINDINGS
In a biopsy study of the sural nerve, damage to C and Aδ fibers were seen in patients who had recent onset of pain in their feet consisting of tingling, burning, and prickling, followed by initial demyelination/remyelination of large fibers. DPN is characterized by a pattern of distal-to-proximal axonal loss with symptoms. Hyperglycemia and dyslipidemia are the primary causes of DPN in patients with type 1 and 2 diabetes, respectively. The pattern of pain from DPN is described as "glove and stocking". DPN-induced pain is described as burning, electric, sharp, and dull aching with various pain intensities. DPN is a diagnosis of exclusion; diagnosis is made with a thorough medical history, physical examination, and clinical testing to rule out other causes of pain. Anticonvulsants (pregabalin and gabapentin), antidepressants (duloxetine, venlafaxine, and amitriptyline), opioids (tramadol, tapentadol, and oxycodone), and topical capsaicin are commonly administered to treat DPN. The combination of two or three of these pharmacological agents better resolves pain at lower doses and with fewer side effects.
CONCLUSIONS
Clinicians should have sufficient knowledge of DPN to ensure its accurate diagnosis and appropriate treatment. This review provides clinicians with the necessary knowledge of the pathophysiology, diagnosis, and treatment of painful DPN.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 1; Quality of Life; Diabetes Mellitus, Type 2; Pain
PubMed: 36786097
DOI: 10.21037/apm-22-693 -
Drugs Jul 2021We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical...
We conducted a narrative review of the literature to compare the pharmacological, efficacy and safety profiles of tapentadol and tramadol, and to assess the clinical interest of tapentadol in adult patients. Tapentadol and tramadol share a mixed mechanism of action, including both mu-agonist and monoaminergic properties. Tapentadol is approximately two to three times more potent than tramadol and two to three times less potent than morphine. It has no identified analgesically active metabolite and is not significantly metabolised by cytochrome P450 enzymes, thus overcoming some limitations of tramadol, including the potential for pharmacokinetic drug-drug interactions and interindividual variability due to genetic polymorphisms of cytochrome P450 enzymes. The toxicity profiles of tramadol and tapentadol are similar; however tapentadol is likely to result in less exposure to serotoninergic adverse effects (nausea, vomiting, hypoglycaemia) but cause more opioid adverse effects (constipation, respiratory depression, abuse) than tramadol. The safety of tapentadol in real-world conditions remains poorly documented, particularly in at-risk patient subgroups and also in the ability to assess the risk associated with its residual serotonergic activity (serotonin syndrome, seizures). Because of an earlier market introduction, more real-world safety data are available for tramadol, including data from at-risk patient subgroups. The level of evidence on the efficacy of both tramadol and tapentadol for the treatment of chronic pain is globally low. The trials published to date show overall that tapentadol does not provide a clinically significant analgesic improvement compared to existing treatments, for which the safety profile is much better known. In conclusion, tapentadol is not a first-line opioid but represents an additional analgesic in the therapeutic choices, which some patients may benefit from after careful examination of their clinical situation, co-morbidities and co-medications.
Topics: Analgesics, Opioid; Cytochrome P-450 CYP2D6; Dose-Response Relationship, Drug; Humans; Liver Failure; Pain; Renal Insufficiency; Tapentadol; Tramadol
PubMed: 34196947
DOI: 10.1007/s40265-021-01515-z -
The Cochrane Database of Systematic... Jul 2017Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their... (Review)
Review
BACKGROUND
Pain is a common symptom with cancer, and 30% to 50% of all people with cancer will experience moderate to severe pain that can have a major negative impact on their quality of life. Opioid (morphine-like) drugs are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. The most commonly-used opioid drugs are buprenorphine, codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, tramadol, and tapentadol.
OBJECTIVES
To provide an overview of the analgesic efficacy of opioids in cancer pain, and to report on adverse events associated with their use.
METHODS
We identified systematic reviews examining any opioid for cancer pain published to 4 May 2017 in the Cochrane Database of Systematic Reviews in the Cochrane Library. The primary outcomes were no or mild pain within 14 days of starting treatment, withdrawals due to adverse events, and serious adverse events.
MAIN RESULTS
We included nine reviews with 152 included studies and 13,524 participants, but because some studies appeared in more than one review the number of unique studies and participants was smaller than this. Most participants had moderate or severe pain associated with a range of different types of cancer. Studies in the reviews typically compared one type of opioid or formulation with either a different formulation of the same opioid, or a different opioid; few included a placebo control. Typically the reviews titrated dose to effect, a balance between pain relief and adverse events. Various routes of administration of opioids were considered in the reviews; oral with most opioids, but transdermal administration with fentanyl, and buprenorphine. No review included studies of subcutaneous opioid administration. Pain outcomes reported were varied and inconsistent. The average size of included studies varied considerably between reviews: studies of older opioids, such as codeine, morphine, and methadone, had low average study sizes while those involving newer drugs tended to have larger study sizes.Six reviews reported a GRADE assessment (buprenorphine, codeine, hydromorphone, methadone, oxycodone, and tramadol), but not necessarily for all comparisons or outcomes. No comparative analyses were possible because there was no consistent placebo or active control. Cohort outcomes for opioids are therefore reported, as absolute numbers or percentages, or both.Reviews on buprenorphine, codeine with or without paracetamol, hydromorphone, methadone, tramadol with or without paracetamol, tapentadol, and oxycodone did not have information about the primary outcome of mild or no pain at 14 days, although that on oxycodone indicated that average pain scores were within that range. Two reviews, on oral morphine and transdermal fentanyl, reported that 96% of 850 participants achieved that goal.Adverse event withdrawal was reported by five reviews, at rates of between 6% and 19%. Participants with at least one adverse event were reported by three reviews, at rates of between 11% and 77%.Our GRADE assessment of evidence quality was very low for all outcomes, because many studies in the reviews were at high risk of bias from several sources, including small study size.
AUTHORS' CONCLUSIONS
The amount and quality of evidence around the use of opioids for treating cancer pain is disappointingly low, although the evidence we have indicates that around 19 out of 20 people with moderate or severe pain who are given opioids and can tolerate them should have that pain reduced to mild or no pain within 14 days. This accords with the clinical experience in treating many people with cancer pain, but overstates to some extent the effectiveness found for the WHO pain ladder. Most people will experience adverse events, and help may be needed to manage the more common undesirable adverse effects such as constipation and nausea. Perhaps between 1 in 10 and 2 in 10 people treated with opioids will find these adverse events intolerable, leading to a change in treatment.
Topics: Acetaminophen; Administration, Cutaneous; Administration, Oral; Analgesics, Opioid; Buprenorphine; Cancer Pain; Codeine; Fentanyl; Humans; Hydromorphone; Methadone; Oxycodone; Phenols; Review Literature as Topic; Tapentadol; Tramadol
PubMed: 28683172
DOI: 10.1002/14651858.CD012592.pub2 -
Diabetes & Metabolism Journal Nov 2023Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%-25% of... (Review)
Review
Diabetic peripheral neuropathy (DPN) is one of the most prevalent chronic complications of diabetes. The lifetime prevalence of DPN is thought to be >50%, and 15%-25% of patients with diabetes experience neuropathic pain, referred to as "painful DPN." Appropriate treatment of painful DPN is important because this pain contributes to a poor quality of life by causing sleep disturbance, anxiety, and depression. The basic principle for the management of painful DPN is to control hyperglycemia and other modifiable risk factors, but these may be insufficient for preventing or improving DPN. Because there is no promising diseasemodifying medication for DPN, the pain itself needs to be managed when treating painful DPN. Drugs for neuropathic pain, such as gabapentinoids, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, alpha-lipoic acid, sodium channel blockers, and topical capsaicin, are used for the management of painful DPN. The U.S. Food and Drug Administration (FDA) has approved pregabalin, duloxetine, tapentadol, and the 8% capsaicin patch as drugs for the treatment of painful DPN. Recently, spinal cord stimulation using electrical stimulation is approved by the FDA for the treatment for painful DPN. This review describes the currently available pharmacological and nonpharmacological treatments for painful DPN.
Topics: United States; Humans; Diabetic Neuropathies; Capsaicin; Quality of Life; Duloxetine Hydrochloride; Neuralgia; Diabetes Mellitus
PubMed: 37670573
DOI: 10.4093/dmj.2023.0018 -
Clinical Medicine (London, England) Feb 2018Pain is a common symptom in many types of cancer. Interdisciplinary team management, including pain assessment, explanation to the patient/family, treating the... (Review)
Review
Pain is a common symptom in many types of cancer. Interdisciplinary team management, including pain assessment, explanation to the patient/family, treating the reversible, non-pharmacological treatments and reassessment are essential. This article focuses on the pharmacological management of cancer pain, and overviews and updates on the recent advances in this field. Both non-opioid and opioid analgesia as well as coanalgesics (adjuvants) are reviewed. Within non-opioid analgesia the risks of non-steroidal anti-inflammatory drugs (NSAIDs) are considered and recommendations for NSAIDs in patients at risk of gastrointestinal and cardiovascular toxicity are made. For opioid analgesics, side effects of opioids are discussed alongside practical guidance on opioid prescribing and converting between opioids. Newer drugs such as tapentadol are considered in this update. Amitriptyline, duloxetine, gabapentin and pregabalin, and the guidance for their use are reviewed in the coanalgesics (adjuvants) section.
Topics: Cancer Pain; Humans; Medication Therapy Management; Pain Management; Pain Measurement; Palliative Care
PubMed: 29436434
DOI: 10.7861/clinmedicine.18-1-17 -
The Cochrane Database of Systematic... Apr 2017Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic pain is defined as pain lasting beyond normal tissue healing time, generally taken to be 12 weeks. It contributes to disability, anxiety, depression, sleep disturbances, poor quality of life, and healthcare costs. Chronic pain has a weighted mean prevalence in adults of 20%.For many years, the treatment choice for chronic pain included recommendations for rest and inactivity. However, exercise may have specific benefits in reducing the severity of chronic pain, as well as more general benefits associated with improved overall physical and mental health, and physical functioning.Physical activity and exercise programmes are increasingly being promoted and offered in various healthcare systems, and for a variety of chronic pain conditions. It is therefore important at this stage to establish the efficacy and safety of these programmes, and furthermore to address the critical factors that determine their success or failure.
OBJECTIVES
To provide an overview of Cochrane Reviews of adults with chronic pain to determine (1) the effectiveness of different physical activity and exercise interventions in reducing pain severity and its impact on function, quality of life, and healthcare use; and (2) the evidence for any adverse effects or harm associated with physical activity and exercise interventions.
METHODS
We searched theCochrane Database of Systematic Reviews (CDSR) on the Cochrane Library (CDSR 2016, Issue 1) for systematic reviews of randomised controlled trials (RCTs), after which we tracked any included reviews for updates, and tracked protocols in case of full review publication until an arbitrary cut-off date of 21 March 2016 (CDSR 2016, Issue 3). We assessed the methodological quality of the reviews using the AMSTAR tool, and also planned to analyse data for each painful condition based on quality of the evidence.We extracted data for (1) self-reported pain severity, (2) physical function (objectively or subjectively measured), (3) psychological function, (4) quality of life, (5) adherence to the prescribed intervention, (6) healthcare use/attendance, (7) adverse events, and (8) death.Due to the limited data available, we were unable to directly compare and analyse interventions, and have instead reported the evidence qualitatively.
MAIN RESULTS
We included 21 reviews with 381 included studies and 37,143 participants. Of these, 264 studies (19,642 participants) examined exercise versus no exercise/minimal intervention in adults with chronic pain and were used in the qualitative analysis.Pain conditions included rheumatoid arthritis, osteoarthritis, fibromyalgia, low back pain, intermittent claudication, dysmenorrhoea, mechanical neck disorder, spinal cord injury, postpolio syndrome, and patellofemoral pain. None of the reviews assessed 'chronic pain' or 'chronic widespread pain' as a general term or specific condition. Interventions included aerobic, strength, flexibility, range of motion, and core or balance training programmes, as well as yoga, Pilates, and tai chi.Reviews were well performed and reported (based on AMSTAR), and included studies had acceptable risk of bias (with inadequate reporting of attrition and reporting biases). However the quality of evidence was low due to participant numbers (most included studies had fewer than 50 participants in total), length of intervention and follow-up (rarely assessed beyond three to six months). We pooled the results from relevant reviews where appropriate, though results should be interpreted with caution due to the low quality evidence. Pain severity: several reviews noted favourable results from exercise: only three reviews that reported pain severity found no statistically significant changes in usual or mean pain from any intervention. However, results were inconsistent across interventions and follow-up, as exercise did not consistently bring about a change (positive or negative) in self-reported pain scores at any single point. Physical function: was the most commonly reported outcome measure. Physical function was significantly improved as a result of the intervention in 14 reviews, though even these statistically significant results had only small-to-moderate effect sizes (only one review reported large effect sizes). Psychological function and quality of life: had variable results: results were either favourable to exercise (generally small and moderate effect size, with two reviews reporting significant, large effect sizes for quality of life), or showed no difference between groups. There were no negative effects. Adherence to the prescribed intervention: could not be assessed in any review. However, risk of withdrawal/dropout was slightly higher in the exercising group (82.8/1000 participants versus 81/1000 participants), though the group difference was non-significant. Healthcare use/attendance: was not reported in any review. Adverse events, potential harm, and death: only 25% of included studies (across 18 reviews) actively reported adverse events. Based on the available evidence, most adverse events were increased soreness or muscle pain, which reportedly subsided after a few weeks of the intervention. Only one review reported death separately to other adverse events: the intervention was protective against death (based on the available evidence), though did not reach statistical significance.
AUTHORS' CONCLUSIONS
The quality of the evidence examining physical activity and exercise for chronic pain is low. This is largely due to small sample sizes and potentially underpowered studies. A number of studies had adequately long interventions, but planned follow-up was limited to less than one year in all but six reviews.There were some favourable effects in reduction in pain severity and improved physical function, though these were mostly of small-to-moderate effect, and were not consistent across the reviews. There were variable effects for psychological function and quality of life.The available evidence suggests physical activity and exercise is an intervention with few adverse events that may improve pain severity and physical function, and consequent quality of life. However, further research is required and should focus on increasing participant numbers, including participants with a broader spectrum of pain severity, and lengthening both the intervention itself, and the follow-up period.
Topics: Adult; Chronic Pain; Exercise Therapy; Health Services Needs and Demand; Humans; Myalgia; Pain Measurement; Patient Compliance; Quality of Life; Randomized Controlled Trials as Topic; Review Literature as Topic
PubMed: 28436583
DOI: 10.1002/14651858.CD011279.pub3 -
The anaesthetist, opioid analgesic drugs, and serotonin toxicity: a mechanistic and clinical review.British Journal of Anaesthesia Jan 2020Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin... (Review)
Review
Most cases of serotonin toxicity are provoked by therapeutic doses of a combination of two or more serotonergic drugs, defined as drugs affecting the serotonin neurotransmitter system. Common serotonergic drugs include many antidepressants, antipsychotics, and opioid analgesics, particularly fentanyl, tramadol, meperidine (pethidine), and methadone, but rarely morphine and other related phenanthrenes. Symptoms of serotonin toxicity are attributable to an effect on monoaminergic transmission caused by an increased synaptic concentration of serotonin. The serotonin transporter (SERT) maintains low serotonin concentrations and is important for the reuptake of the neurotransmitter into the presynaptic nerve terminals. Some opioids inhibit the reuptake of serotonin by inhibiting SERT, thus increasing the plasma and synaptic cleft serotonin concentrations that activate the serotonin receptors. Opioids that are good inhibitors of SERT (tramadol, dextromethorphan, methadone, and meperidine) are most frequently associated with serotonin toxicity. Tramadol also has a direct serotonin-releasing action. Fentanyl produces an efflux of serotonin, and binds to 5-hydroxytryptamine (5-HT) and 5-HT receptors, whilst methadone, meperidine, and more weakly tapentadol, bind to 5-HT but not 5-HT receptors. The perioperative period is a time where opioids and other serotonergic drugs are frequently administered in rapid succession, sometimes to patients with other serotonergic drugs in their system. This makes the perioperative period a relatively risky time for serotonin toxicity to occur. The intraoperative recognition of serotonin toxicity is challenging as it can mimic other serious syndromes, such as malignant hyperthermia, sepsis, thyroid storm, and neuroleptic malignant syndrome. Anaesthetists must maintain a heightened awareness of its possible occurrence and a readiness to engage in early treatment to avoid poor outcomes.
Topics: Analgesics, Opioid; Anesthesiologists; Fever; Humans; Intraoperative Complications; Serotonin Agents; Serotonin Syndrome
PubMed: 31653394
DOI: 10.1016/j.bja.2019.08.010 -
Pain Research & Management 2014Neuropathic pain (NeP), redefined as pain caused by a lesion or a disease of the somatosensory system, is a disabling condition that affects approximately two million...
BACKGROUND
Neuropathic pain (NeP), redefined as pain caused by a lesion or a disease of the somatosensory system, is a disabling condition that affects approximately two million Canadians.
OBJECTIVE
To review the randomized controlled trials (RCTs) and systematic reviews related to the pharmacological management of NeP to develop a revised evidence-based consensus statement on its management.
METHODS
RCTs, systematic reviews and existing guidelines on the pharmacological management of NeP were evaluated at a consensus meeting in May 2012 and updated until September 2013. Medications were recommended in the consensus statement if their analgesic efficacy was supported by at least one methodologically sound RCT (class I or class II) showing significant benefit relative to placebo or another relevant control group. Recommendations for treatment were based on the degree of evidence of analgesic efficacy, safety and ease of use.
RESULTS
Analgesic agents recommended for first-line treatments are gabapentinoids (gabapentin and pregabalin), tricyclic antidepressants and serotonin noradrenaline reuptake inhibitors. Tramadol and controlled-release opioid analgesics are recommended as second-line treatments for moderate to severe pain. Cannabinoids are now recommended as third-line treatments. Recommended fourth-line treatments include methadone, anticonvulsants with lesser evidence of efficacy (eg, lamotrigine, lacosamide), tapentadol and botulinum toxin. There is support for some analgesic combinations in selected NeP conditions.
CONCLUSIONS
These guidelines provide an updated, stepwise approach to the pharmacological management of NeP. Treatment should be individualized for each patient based on efficacy, side-effect profile and drug accessibility, including cost. Additional studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics, long-term outcomes and treatment of pediatric, geriatric and central NeP.
Topics: Analgesics; Canada; Chronic Pain; Humans; Neuralgia; Pain Management
PubMed: 25479151
DOI: 10.1155/2014/754693