Analgesic Pharmacotherapy Research Articles

Treating Chronic Tendinopathy: Physical Therapy, Surgery and Other Form of Therapy

Introduction: The term "tendinopathy" refers to pathological changes in tendons. The previously used term "tendonitis" does not fully capture the nature of the condition, as inflammatory changes, when present, are secondary to degenerative damage. Tendinopathies are quite common in the general population. Aim: The aim of this review is to characterize various types of tendinopathies, with a focus on both conservative and surgical treatment methods, in order to organize available information that may be helpful for clinicians in their practice. State of Knowledge: Chronic tendinopathies develop as a result of multiple factors. The most significant include improper exercise techniques, excessive strain, and musculoskeletal system abnormalities. Summary (Conclusions): The approach to tendinopathy treatment should vary depending on the patient's clinical condition and provoking factors. Physiotherapy plays the most important role, along with supportive methods such as analgesic pharmacotherapy and cryotherapy. Surgical intervention may be necessary in cases where conservative treatment fails.

Analgesic Use Among Adults with a Trauma-Related Emergency Department Visit: A Retrospective Cohort Study from Alberta, Canada.

A better understanding of current acute pain-driven analgesic practices within the emergency department (ED) and upon discharge will provide foundational information in this area, as few studies have been conducted in Canada. Administrative data were used to identify adults with a trauma-related ED visit in the Edmonton area in 2017/2018. Characteristics of the ED visit included time from initial contact to analgesic administration, type of analgesics dispensed during and upon being discharged home directly from the ED (≤ 7days after), and patient characteristics. A total of 50,950 ED visits by 40,505 adults with trauma were included. Analgesics were administered in 24.2% of visits, of which non-opioids were dispensed in 77.0% and opioids were dispensed in 49.0%. Time to analgesic initiation occurred more than 2h after first contact. Upon discharge, 11.5% received a non-opioid and 15.2% received an opioid analgesic, among whom 18.5% received a daily dose ≥ 50 morphine milligram equivalents (MME) and 30.2% received > 7 days of supply. Three hundred and seventeen adults newly met criteria for chronic opioid use after the ED visit, among whom 43.5% received an opioid dispensation upon discharge; of these individuals, 26.8% had a daily dose ≥ 50 MME and 65.9% received > 7days of supply. Findings can be used to inform optimization of analgesic pharmacotherapy practices for the treatment of acute pain, which may include reducing the time to initiation of analgesics in the ED, as well as close consideration of recommendations for acute pain management upon discharge to provide ideal patient-centered, evidence-informed care.

ORAL MICROBIOME INFLUENCES THE CLINICAL COURSE OF ORAL MUCOSITIS IN ALLOGENEIC HSCT PATIENTS

<h3>Objectives</h3> Oral mucositis (OM) is a complex acute cytotoxicity of antineoplastic treatment that affects 40% to 85% of patients undergoing hematopoietic stem cell transplantation. Clinically, OM is characterized by redness or ulceration covered by a pseudomembrane of cellular debris and bacterial colonies that usually develops within 5 to 7 days after the conditioning drug's administration. Incidence of OM is associated with prolonged hospitalization, extensive analgesic pharmacotherapy, parenteral nutrition, and elevated treatment costs. In this context, the identification of patient risks for OM is fundamental to enhance supportive care in oncology. OM onset relies on mucosal microenvironment status, with a possible role of microbiota-driven inflammation. We aimed to investigate whether the oral mucosa microbiota was associated with the clinical course of OM. <h3>Study Design</h3> We collected oral mucosa samples from 30 patients undergoing allogeneic hematopoietic stem cell transplantation at preconditioning. During the period of the study, 13 of 30 patients developed OM. For those patients, additional oral mucosa samples were collected at OM ulceration onset and ulcerated OM healing. All samples were characterized by 16S rRNA sequencing. <h3>Results</h3> We observed that specific taxa were associated with OM risk, severity, and time to resolution. In particular, at preconditioning, higher relative abundance of <i>Lactococcus</i> was associated with an increased ulcerated OM risk (75% vs 33%; <i>P</i> = .034), and the relative abundance of <i>Porphyromonas</i> was positively correlated with ulcerated OM grade (rho = 0.605, <i>P</i> = .028). Additionally, we observed that higher relative abundance of <i>Solobacterium</i> at OM onset was associated with prolonged OM ulcerated duration (<i>P</i> = .0005), whereas higher relative abundance of <i>Lactobacillus</i> was associated with shortened ulcerated OM duration (<i>P</i> = .032). <h3>Conclusions</h3> This was the first study to investigate oral mucosa taxa as biomarkers for OM clinical course in patients undergoing allogeneic hematopoietic stem cell transplantation. Our findings suggest that further research should focus on evaluating the influence of host-microbiome interactions on OM pathophysiology.

Outpatient Oral Neuropathic Pain Management with Photobiomodulation Therapy: A Prospective Analgesic Pharmacotherapy-Paralleled Feasibility Trial.

Neuropathic pain (NP) can be challenging to treat effectively as analgesic pharmacotherapy (MED) can reduce pain, but the majority of patients do not experience complete pain relief. Our pilot approach is to assess the feasibility and efficacy of an evidence-based photobiomodulation (PBM) intervention protocol. This would be as an alternative to paralleled standard analgesic MED for modulating NP intensity-related physical function and quality of life (QoL) prospectively in a mixed neurological primary burning mouth syndrome and oral iatrogenic neuropathy study population (n = 28). The study group assignments and outcome evaluation strategy/location depended on the individual patient preferences and convenience rather than on randomisation. Our prospective parallel study aimed to evaluate the possible pre/post-benefit of PBM and to allow for a first qualitative comparison with MED, various patient-reported outcome measures (PROMs) based on Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT-II) were used for up to a nine-month follow-up period in both intervention groups (PBM and MED). The PBM protocol applied to the PBM group was as follows: λ810 nm, 200 mW, 0.088 cm2, 30 s/point, 9 trigger and affected points, twice a week for five consecutive weeks, whereas the MED protocol followed the National Institute of Clinical Excellence (NICE) guidelines. Our results showed that despite the severe and persistent nature of the symptoms of 57.50 ± 47.93 months at baseline in the PBM group, a notably rapid reduction in PISmax on VAS from 7.6 at baseline (T0) to 3.9 at one-month post-treatment (T3) could be achieved. On the other hand, mean PISmax was only reduced from 8.2 at baseline to 6.8 at T3 in the MED group. Our positive PBM findings furthermore support more patients’ benefits in improving QoL and functional activities, which were considerably impaired by NP such as: eating, drinking and tasting, whereas the analgesic medication regimens did not. No adverse events were observed in both groups. To the best knowledge of the authors, our study is the first to investigate PBM efficacy as a monotherapy compared to the gold standard analgesic pharmacotherapy. Our positive data proves statistically significant improvements in patient self-reported NP, functionality, psychological profile and QoL at mid- and end-treatment, as well as throughout the follow-up time points (one, three, six and nine months) and sustained up to nine months in the PBM group, compared to the MED group. Our study, for the first time, proves the efficacy and safety of PBM as a potent analgesic in oral NP and as a valid alternative to the gold standard pharmacotherapy approach. Furthermore, we observed long-term pain relief and functional benefits that indicate that PBM modulates NP pathology in a pro-regenerative manner, presumably via antioxidant mechanisms.

4 przypadki kliniczne chorych, u których warto rozważyć zastosowanie połączenia chondroityny z glukozaminą

Osteoarthritis is a chronic disease that affects mainly the elderly. The primary form of therapy is analgesic pharmacotherapy in accordance with the analgesic ladder. Another, still controversial, method is the administration of symptomatic slow-acting drugs for osteoarthritis, the main advantage of which is that they are practically devoid of toxicity. A recent review of papers on the use of this group of drugs has shown that the most potent modifying effect has the combination of glucosamine and chondroitin, which synergistically change the metabolism of the articular cartilage. In this article, we present four clinical cases in which the combination of glucosamine and chondroitin was effective.

Analysis of in-hospital analgesic pharmacotherapy costs and regimen and impact on postoperative pain-related function in degenerative lumbar intervertebral disc disease

BackgroundPain medication may affect clinical and economic outcomes, and a detailed description of pain medication use is advocated in the literautre for better assessment of clinical outcomes of spine surgery, which otherwise clould be misleading. ObjectivesTo analyze the impact of in-hospital analgesic pharmacotherapy after spine surgery on subjective quality of life and pain relief in patients with degenerative lumbar intervertebral disc disease (DLIVD), and also to analyze pharmacotherapy costs. DesignA single-center study included 50 patients with L5/S1 or L4/L5 DLIVD, eligible for spine surgery. InterventionNeurosurgery for DLIVD. Main endpointsOutcomes in terms of postoperative pain and function were recorded prospectively using standardized questionnaires. Data for cost analysis and pharmcotherapy regimen were obtained retrospectively from case histories, doctors’ request cards and hospital discharge summaries. ResultsMean total pharmacotherapy cost amounted to €453.42±49.09. Mean pharmacotherapy cost amounted to €314.76±54.21 preoperatively, and €138.66±25.54 postoperatively. The greatest improvement in function and quality of life was in patients treated with non-opioids. ConclusionThis study supports the notion that analgesic pharmacotherapies could be differentiated in terms of overall impact on quality of life, and that pain-related distress might be the most relevant factor in this setting.

Pain in the neurodegenerating brain: insights into pharmacotherapy for Alzheimer disease and Parkinson disease.

Pain in the neurodegenerating brain: insights into pharmacotherapy for Alzheimer disease and Parkinson disease.

Functional pain disorders - more than nociplastic pain.

Nociplastic pain has been recently introduced as a third mechanistic descriptor of pain arising primarily from alterations of neural processing, in contrast to pain due to tissue damage leading to nociceptor activation (nociceptive) or due to lesion or disease of the somatosensory nervous system (neuropathic). It is characterized by hyperalgesia and allodynia, inconsistency and reversibility, as well as dynamic cross-system interactions with biological and psychobehavioral factors. Along with this renewed understanding, functional pain disorders, also classified as chronic primary pain, are being reframed as biopsychosocial conditions that benefit from multimodal treatment. To summarize the current understanding of nociplastic pain and functional pain disorders, with a focus on conditions that are common in neurology practice. This was a narrative literature review. Chronic back pain, fibromyalgia syndrome and complex regional pain syndrome are best understood within a biopsychosocial framework of pain perception that considers structural factors (predispositions and sequelae) and psychobehavioral mechanisms. Although pain is often the primary complaint, it should not be the only focus of treatment, as accompanying symptoms such as sleep or mood problems can significantly impact quality of life and offer useful leverage points for multimodal treatment. Analgesic pharmacotherapy is rarely helpful on its own, and should always be imbedded in a multidisciplinary setting.

Adverse childhood experiences predict autonomic indices of emotion dysregulation and negative emotional cue-elicited craving among female opioid-treated chronic pain patients.

Through autonomic and affective mechanisms, adverse childhood experiences (ACEs) may disrupt the capacity to regulate negative emotions, increasing craving and exacerbating risk for opioid use disorder (OUD) among individuals with chronic pain who are receiving long-term opioid analgesic pharmacotherapy. This study examined associations between ACEs, heart rate variability (HRV) during emotion regulation, and negative emotional cue-elicited craving among a sample of female opioid-treated chronic pain patients at risk for OUD. A sample of women (N = 36, mean age = 51.2 ± 9.5) with chronic pain receiving long-term opioid analgesic pharmacotherapy (mean morphine equivalent daily dose = 87.1 ± 106.9 mg) were recruited from primary care and pain clinics to complete a randomized task in which they viewed and reappraised negative affective stimuli while HRV and craving were assessed. Both ACEs and duration of opioid use significantly predicted blunted HRV during negative emotion regulation and increased negative emotional cue-elicited craving. Analysis of study findings from a multiple-levels-of-analysis approach suggest that exposure to childhood abuse occasions later emotion dysregulation and appetitive responding toward opioids in negative affective contexts among adult women with chronic pain, and thus this vulnerable clinical population should be assessed for OUD risk when initiating a course of extended, high-dose opioids for pain management.

Trigeminal Neuralgia: Medical Management and Surgical Options

Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. In response to a question about trigeminal neuralgia, its diagnosis, medical therapies, surgical procedures, and treatment outcomes will be discussed.

Impact of hydrocodone reclassification on analgesic prescribing in the Veterans Health Administration.

The impact of hydrocodone reclassification on analgesic prescribing in the Veterans Health Administration (VHA) was quantified. In this retrospective observational study, the volume of opioid medication dispensed was calculated quarterly from October 2011 to September 2015 using national VHA administrative data. Four volume measures were examined (prescription count, tablets dispensed, days' supply dispensed, and unique patients) for 4 opioid groups: hydrocodone combination products (HCPs), other opioid combination products, tramadol, and single-agent Schedule II opioids. HCP prescription count was further tabulated within longitudinal course of receipt groups: short-term, intermediate-term, and long-term. The initiation frequency of alternative analgesic pharmacotherapy, including opioid and nonopioid medications, was assessed among patients who discontinued long-term HCP receipt at reclassification. HCP prescriptions declined by 172,535 (19.4%) in the quarter after reclassification, whereas other opioid categories remained unchanged. The number of HCP prescriptions decreased by 10.7% among patients with short-term opioid receipt, and by 23.3% and 19.4% for intermediate- and long-term receipt groups, respectively. Among 13,416 individuals who discontinued receipt of long-term HCPs, replacement analgesics were not identified in 8,055 (60.0%) patients, whereas prescriptions for alternative opioids were observed in 3,557 (26.5%) and nonopioids in 2,753 (20.5%). HCP dispensing in VHA declined by 19.4% in the quarter after reclassification, which was driven largely by patients receiving long-term therapy. More than 13,000 veterans discontinued receipt of long-term HCP therapy after reclassification and the majority did not receive a replacement analgesic through VHA.

Impact of a pharmacist-directed pain management service on inpatient opioid use, pain control, and patient safety.

To evaluate the impact of a pharmacy-directed pain management service (PPMS) designed to optimize analgesic pharmacotherapy, minimize adverse events, and improve patients' experience of pain management. A retrospective analysis was conducted to evaluate the PPMS consisting of 3 dedicated pain management clinical pharmacists who perform both consult-based and stewardship functions. Multiple measures of opioid use and associated patient satisfaction outcomes during 3-year periods before and after implementation of the PPMS were compared. Significant decreases in use of institutionally defined high-risk opioid medications (e.g., parenteral hydromorphone, fentanyl, transdermal fentanyl patches), a decrease in total institutional opioid use, increased coanalgesic and adjunctive medication use, and a decrease in rapid response team (RRT) and code blue events associated with opioid-induced oversedation were seen after service implementation. Despite decreased opioid use, available patient satisfaction data suggested ongoing improvement in associated Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey domains. Our data highlights the impact of a pharmacy directed pain management service on institutional opioid use with available data suggesting improved patient satisfaction scores and indirect cost savings. Despite decreased opioid use, available patient satisfaction data suggested ongoing improvement in associated HCAHPS survey pain management domains.

Things to Consider When Completing an Advance Directive

Questions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. In response to a question about advance directives for a patient experiencing chronic pain, the authors discuss the importance of having legal documents in place.

Neuropathic pain is not adequately treated in the older general population: Results from the KORA F4 survey.

We evaluated the pharmacological treatment of distal sensorimotor polyneuropathy (DSPN) among older subjects from the general population. The study included subjects aged 61 to 82years from the KORA F4 survey (2006-2008). DSPN was defined as the presence of bilaterally impaired foot-vibration perception and/or bilaterally impaired foot-pressure sensation. Pain intensity was assessed with the painDETECT questionnaire. From the included 1076 older persons, 172 (16%) persons reported pain in the lower extremities and DSPN was present in 150 (14%) subjects. Forty-eight people with pain in the lower extremities reported DSPN. Only 38% of the subjects with DSPN reporting an average pain level of ≥4 during the past 4weeks received medical treatment, predominantly nonsteroidal anti-inflammatory drugs (NSAIDs 20% and opioids 12%). The medication of choice for neuropathic pain, antidepressants, anticonvulsants, and opioids was relatively being underused. However, opioids and neuropathy preparations were prescribed preferably for subjects with painful DSPN. In the older general population, only a small proportion of subjects with painful DSPN receive analgesic pharmacotherapy. Although not recommended by guidelines for the treatment of neuropathic pain, NSAIDs were the most frequently used class of analgesic drugs.

Clinician Referrals for Non-opioid Pain Care Following Discontinuation of Long-term Opioid Therapy Differ Based on Reasons for Discontinuation.

Little is known about pain care offered to patients discontinued from long-term opioid therapy (LTOT) by their prescriber due to aberrant behaviors versus other reasons. This study aimed to compare rates of non-opioid analgesic pharmacotherapy initiation and clinician referrals for non-pharmacologic pain treatment, complementary and integrative pain therapies, and specialty mental health and substance use disorder treatment between patients discontinued from opioid therapy due to aberrant behaviors versus other reasons. The design included retrospective manual electronic health record review and administrative data abstraction. Patients were sampled from a national cohort of US Department of Veterans Affairs patients prescribed continuous opioid therapy in 2011 who subsequently discontinued opioid therapy in 2012. The study sample comprised 509 patients discontinued from LTOT by opioid-prescribing clinicians. The primary independent variable was reason for discontinuation of LTOT (aberrant behaviors versus other reasons). Pain care dichotomous outcomes included clinician use of an opioid taper; initiating new non-opioid analgesic pharmacotherapy; and referrals for non-pharmacologic pain treatment, complementary and integrative pain therapies, and specialty mental health and substance use disorder treatment. We observed low rates of opioid taper (15% of patients), initiations of new or modifications of existing non-opioid analgesic pharmacotherapy (45% of patients), and clinician referrals for non-pharmacologic pain treatment (58% of patients) and complementary and integrative therapies (25% of patients). Patients discontinued due to aberrant behaviors, relative to patients discontinued for other reasons, were more likely to receive opioid tapers (adjusted OR = 5.60, 95% CI = 2.10-14.93), receive new non-opioid analgesic medications or dose changes to an existing non-opioid analgesic medications (adjusted OR = 2.61, 95% CI = 1.59-4.29), or be referred for specialty substance use disorder treatment (adjusted OR = 7.39, 95% CI = 3.76-14.53). These findings highlight the variability in referral rates for different types of non-opioid pain treatments and challenges accessing specific types of pain care.

Reappraisal deficits promote craving and emotional distress among chronic pain patients at risk for prescription opioid misuse

ABSTRACTBackground: A subset of chronic pain patients misuse prescription opioids as a means of regulating negative emotions. However, opioid misuse may result in deficits in emotion regulation strategies like reappraisal by virtue of the deleterious effects of chronic opioid exposure. Aims: The aim of this study was to characterize differences in reappraisal use among chronic pain patients at risk for opioid misuse and those who report taking opioids as prescribed. Methods: A sample of 127 pain patients receiving chronic opioid analgesic pharmacotherapy were classified as at risk for opioid misuse (n = 62) or taking opioids as prescribed (n = 65) using the Current Opioid Misuse Measure (COMM). The Emotion Regulation Questionnaire (ERQ) characterized use of emotion regulation strategies including reappraisal and expressive suppression. Participants also reported levels of opioid craving, emotional distress, and pain severity. Results: Patients at risk for opioid misuse reported significantly less reappraisal use (M = 25.31, SD = 7.33) than those who reportedly took opioids as prescribed (M = 30.28, SD = 7.50), p<.001, but did differ with regard to suppression strategies. Reduced reappraisal use was associated with higher opioid craving and emotional distress that mediated the association between reappraisal deficits and opioid misuse risk. Further, there was a significant indirect effect of opioid misuse on emotional distress via reappraisal use. Discussion: Opioid misuse risk was associated with reduced use of reappraisal, which in turn was associated with dysregulated negative emotions and increased appetitive drive towards consuming opioids. Studying individual differences in emotion regulation may yield efficacious intervention and prevention approaches to stem the rising tide of the prescription opioid crisis.

Antiallodynic activity of leflunomide is partially inhibited by naltrexone and glibenclamide and associated with reduced production of TNF-α and CXCL-1

Leflunomide, an immunosuppressive drug approved for the treatment of patients with rheumatoid arthritis, exhibits many mechanisms which may affect the nociceptive processing. Therefore, the present study aimed to evaluate the effect induced by leflunomide on the mechanical allodynia in models of inflammatory and neuropathic pain in mice and investigate mechanisms mediating such effects. Per os (p.o.) administration of leflunomide (25, 50 or 100mg/kg) inhibited the inflammatory edema and mechanical allodynia induced by intraplantar carrageenan. Even ongoing inflammatory edema and mechanical allodynia were reduced by leflunomide. Previous administration of naltrexone (10mg/kg, intraperitoneal) or glibenclamide (40mg/kg, p.o.) partially attenuated leflunomide antiallodynic activity. A single administration of leflunomide (50 or 100mg/kg, p.o.) also partially inhibited ongoing mechanical allodynia induced by chronic constriction injury (CCI) or repeated administrations of paclitaxel. The antiallodynic effect induced by leflunomide (50 or 100mg/kg, p.o.) in the model of neuropathic pain induced by CCI was associated with reduced production of tumor necrosis factor-α both at the injury site and ipsilateral paw. Leflunomide also reduced production of the chemokine CXCL-1 at the paw ipsilateral to the injury site. Concluding, leflunomide partially inhibited ongoing mechanical allodynia in models of inflammatory and neuropathic pain. The antiallodynic effect was associated with activation of opioidergic receptors and ATP-sensitive potassium channels and reduced production of inflammatory mediators. These data indicate leflunomide as a drug that should be further investigated aiming to identify a new analgesic pharmacotherapy and reinforces repositioning as an important strategy to identify new uses for approved drugs.

The Risks of Chronic Corticosteroid Exposure

ABSTRACTQuestions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. This article focuses on the use of corticosteroids to decrease inflammation and treat painful conditions as well as their long-term side effects and risks. Their long-term use can expose the body to side effects and can cause long-term health concerns. It therefore is important to be aware of the risks of long-term corticosteroid use.

Pathophysiology of Trigger Points in Myofascial Pain Syndrome

ABSTRACTQuestions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. Trigger point pathophysiology in myofascial pain syndrome, which involves muscle stiffness, tenderness, and pain that radiates to other areas of the body, is considered. The causes of trigger points and several theories about how they develop are reviewed, and treatment approaches, including stretching, physical therapy, dry needling, and injections, are offered.

Hypotestosterone and Long-Term Opioid Use

ABSTRACTQuestions from patients about pain conditions and analgesic pharmacotherapy and responses from authors are presented to help educate patients and make them more effective self-advocates. The effects of long-term opioid use on testosterone production, associated comorbidities, and medication-based and natural testosterone replacement therapies are considered.