Long-term Management Of Chronic Pain Research Articles

Current and Emerging Approaches for Pain Management in Hemophilic Arthropathy.

IntroductionHemophilia is an inherited bleeding hematological disorder characterized by the partial or complete deficiency of clotting factor VIII or IX. Hemophilic arthropathy is the consequence of repeated joint bleeding (hemarthrosis) and its management is based on the prevention of acute bleeding through the administration of the deficient clotting factor concentrate or non-factor therapies. In addition, the management of acute and chronic pain is pivotal in hemophilic arthropathy in order to restore function and allow rehabilitation of the joint. MethodsWe conducted a qualitative review of the literature regarding current and emerging strategies for pain treatment in hemophilic arthropathy. This review considers systemic and local pharmacological and non-pharmacological interventions for acute and chronic pain management. ResultsIn hemophilic arthropathy, pain management is based on analgesics such as paracetamol, which represents the first choice for acute and chronic pain in adults and children, in association with opioids for adults. Non-steroidal anti-inflammatory drugs inhibit platelet function, so that the currently preferred drugs are short courses of cyclooxygenase 2 inhibitors. Local treatment with intra-articular injections of corticosteroids is an option for refractory cases and physiotherapy has an important role after hemarthrosis and for the long-term management of chronic pain for both pediatric and adult patients. ConclusionsThe management of pain in hemophilia requires more standardization. Meanwhile, the safest drugs should be used at the lowest effective dosage and for periods as short as possible. For the non-pharmacological management of pain in these patients, a multidisciplinary team including hematologists, orthopedic surgeons, rheumatologists, and physiotherapists is warranted.

Long-term use of nonsteroidal anti-inflammatory drugs for pain control in patients with osteoarthritis: results of the 12-month observational study AELITA (Analgesia: Effective Treatment Using The Therapeutic Algorithm)

Non-steroidal anti-inflammatory drugs (NSAIDs) are the primary means of managing chronic osteoarthritis (OA) pain. The choice of NSAIDs is based on an analysis of the risk of adverse reactions (ARs). Objective: to evaluate the efficacy and safety of long-term use of NSAIDs for pain control in patients with OA in real clinical practice.Patients and methods. To assess the results of long-term use of NSAIDs in OA, a 12-month observational non-interventional study was conducted. It included 611 patients with knee, hip and generalized OA, and nonspecific back pain associated with OA of the facet joints. All patients were prescribed aceclofenac (Aertal®) 200 mg/day. The patients' condition was assessed 2 weeks, 3, 6, 9 and 12 months after the start of therapy. The following parameters were determined: the intensity of pain during movement and the general health assessment (GA) according to the visual analogue scale (VAS, 10 cm); pain intensity according to the Likert verbal rating scale (VRS) (0–4); the number of patients with a pain reduction of ≥50% from baseline; patients' assessment of the result of therapy according to Likert VRS (1–5). The development of ARs was recorded at each visit.Results and discussion. By month 12, 46.8% of patients had dropped out of observation. In patients who continued the study, the average severity of pain according to the VAS at baseline, after 2 weeks, 3, 6, 9 and 12 months was: 6.5±1.2; 4.8±1.4; 3.2±1.4; 2.6±1.4; 2.2±1.1; 1.4±1.1 cm, respectively (significant differences compared to the baseline for all points – p<0.05). The same differences were obtained in GA assessment.Within the indicated time frame, the number of patients with moderate / severe pain (on the Likert scale) decreased from 77.8 to 24.9; 2.9; 2.3; 0.9 and 0%, respectively. The number of patients with a pain reduction of ≥50% from baseline was 12.0; 65.1; 81.0; 88.5 and 84.0%, respectively. A good or excellent assessment of treatment results after 2 weeks was given by 63.3% of patients, and after 12 months – by 95.6%. ARs were observed in about 30% of patients, mainly mild or moderate dyspepsia (in 11.1–23.3%) and arterial hypertension (in 7.1–10.9%). No serious ARs were registered.Conclusion. Aceclofenac is an effective and relatively safe drug for the long-term management of chronic pain in OA.

Expert review and recommendations for the management of acute, chronic, and neuropathic pain in Qatar.

Pain management is an evolving area of expertise in Qatar. Gaps in knowledge, inadequate training for physicians and nurses, and the absence of policies/guidelines are the main barriers to effective pain management in Qatar. In addition, the use of certain pain medication, especially opioids, is highly regulated, limiting their availability in outpatient pain management. These factors are responsible for the undertreatment of pain in Qatar. This study aimed to standardize evidence-based local recommendations for pharmacological treatment of pain in Qatar. An expert panel of physicians from different disciplines, with experience in diagnosis and treatment of the three pain types (i.e., acute, chronic, and neuropathic), was convened for two face-to-face meetings in Doha, Qatar, on November 29, 2019, and on February 22, 2020, with subsequent virtual meetings. A literature search was performed on Medline and Google Scholar databases from inception till December 2019, and all relevant articles were selected. Based on these articles and repeated feedback from the authors, the final pain treatment protocols were developed. Recommendations for the treatment of acute pain, based on pain severity, followed three approaches: acetaminophen/paracetamol or non-steroidal anti-inflammatory drugs (NSAIDs) for mild pain and moderate pain and referral to a pain specialist for severe pain. Acetaminophen/paracetamol or NSAIDs is recommended for chronic pain, and the use of opioids was strongly discouraged because of its long-term side effects. For neuropathic pain, tricyclic antidepressants or gabapentin or pregabalin or serotonin-norepinephrine reuptake inhibitors were recommended first-line agents. Non-responders must be referred to neurologists or a pain specialist. The expert panel provides recommendations for the management of acute, chronic, and neuropathic pain based on international guidelines adapted to local practice and treatment availability in Qatar. More importantly, the panel has recommended taking extreme caution in the use of opioids for long-term management of chronic pain and to refer the patient to a pain specialist clinician as required.

The Safety and Effect of Local Botulinumtoxin A Injections for Long-Term Management of Chronic Pain in Post-Herpetic Neuralgia: Literature Review and Cases Report Treated with Incobotulinumtoxin A.

There are few reports on the safety and effectiveness of long-term botulinumtoxin A (BoNT A) therapy in severe chronic pain of post-herpetic neuralgia (PHN). The literature was searched with the term “neuropathic pain” and “botulinum” on PubMed (up to 29 February 2020). Pain was assessed with the Visual Analogue Scale (VAS) before and after BoNT A therapy. A total of 10 clinical trials and six case reports including 251 patients with PHN were presented. They showed that BoNT A therapy had significant pain reduction (up to 30–50%) and improvement in quality of life. The effect duration seems to be correlated with BoNT A doses injected per injection site. Intervals between BoNT A injections were 10–14 weeks. No adverse events were reported in cases and clinical studies, even in the two pregnant women, whose babies were healthy. The repeated (≥6 times) intra/subcutaneous injections of incobotulinumtoxin A (Xeomin®, Merz Pharmaceuticals, Germany) over the two years of our three cases showed marked pain reduction and no adverse events. Adjunctive local BoNT A injection is a promising option for severe PHN, as a safe and effective therapy in long-term management for chronic neuropathic pain. Its effect size and -duration seem to be depended on the dose of BoNT A injected per each point.

A proof-of-concept study on the impact of a chronic pain and physical activity training workshop for exercise professionals.

Physical activity is essential for long-term chronic pain management, yet individuals struggle to participate. Exercise professionals, including fitness instructors, and personal trainers, are preferred delivery agents for education and instruction on chronic pain, physical activity, and strategies to use adherence-promoting behavioral skills. However, exercise professionals receive no relevant training during certification or continuing education opportunities to effectively support their participants living with chronic pain. Based on the ORBIT model for early pre-efficacy phases of development and testing of new behavioral treatments, the present Phase IIa proof-of-concept study was conducted. The purpose was to examine the impacts of a newly developed chronic pain and physical activity training workshop on psychosocial outcomes among exercise professionals. Outcomes included knowledge and attitudes regarding chronic pain, attitudes and beliefs about the relationship between pain and impairment, and self-efficacy to educate and instruct participants with chronic pain. Forty-eight exercise professionals (Mage=44.4±11.0 years) participated in a three-hour, in-person workshop that was offered at one of four different locations. Participants completed pre- and post-workshop outcome assessment surveys. Mixed MANOVA results comparing time (pre- versus post-workshop) by workshop location (sites 1 to 4) illustrated a significant within-subjects time effect (p<0.001). All outcomes significantly improved from pre- to post-workshop (p's<0.001), demonstrating large effect sizes (partial eta-squared values ranging from 0.45 to 0.59). Findings offer early phase preliminary support for the effectiveness of the chronic pain and physical activity training workshop for exercise professionals. Based on ORBIT model recommendations, findings warrant future phased testing via a pilot randomized clinical trial as well as testing for impacts that trained professionals have on activity adherence among their clients living with chronic pain. Eventual workshop adoption by exercise professional certification organizations would ensure widespread and sustainable access to qualified exercise professionals to help individuals engage in physical activity. By increasing the capacity of available exercise professionals to deliver effective support, active individuals could better manage their chronic pain and live well.

Treatment of chronic pain by designer cells controlled by spearmint aromatherapy.

Current treatment options for chronic pain are often associated with dose-limiting toxicities, or lead to drug tolerance or addiction. Here, we describe a pain management strategy, based on cell-engineering principles and inspired by synthetic biology, consisting of microencapsulated human designer cells that produce huwentoxin-IV (a safe and potent analgesic peptide that selectively inhibits the pain-triggering voltage-gated sodium channel NaV1.7) in response to volatile spearmint aroma and in a dose-dependent manner. Spearmint sensitivity was achieved by ectopic expression of the R-carvone-responsive olfactory receptor OR1A1 rewired via an artificial G-protein deflector to induce the expression of a secretion-engineered and stabilized huwentoxin-IV variant. In a model of chronic inflammatory and neuropathic pain, mice bearing the designer cells showed reduced pain-associated behaviour on oral intake or inhalation-based intake of spearmint essential oil, and absence of cardiovascular, immunogenic and behavioural side effects. Our proof-of-principle findings indicate that therapies based on engineered cells can achieve robust, tunable and on-demand analgesia for the long-term management of chronic pain.

Super-Users at an Acupuncture and Oriental Medicine Teaching Clinic: Demographics and Unique Clinical Characteristics.

The use of acupuncture in the United States has consistently grown over the last two decades, and the National Center for Complementary and Integrative Health has recently called for greater understanding of "real life outcomes and use" by complementary and alternative medicine users. This study assesses the demographics and utilization patterns of "super-users" treated at the Oregon College of Oriental Medicine intern clinic. This was a retrospective chart review at the Oregon College of Oriental Medicine (OCOM) intern clinic, a large acupuncture and oriental medicine (AOM) school in Portland, Oregon. Participants were patients who were treated 100+ times at the OCOM between August 6, 2002, and 2012. The outcome measures were demographic and treatment characteristics, including sex, age, chief complaint, income, medication use, and visit patterns. The super-user cohort comprised approximately 1.5% of the total annual patient population and 8% of total visits at the OCOM in any given year, with an average treatment duration of 4 years from visit 1 to visit 100, and a visit frequency of 32 visits per year. Similar to other studies, the super-user cohort consisted predominantly of older, female patients seeking treatment primarily for pain (57.3%). Prescription medication use (45.2%) was also similar to other acupuncture cohorts. In contrast to typical AOM patients, OCOM super-users were older, with 64% being age ≥50 years when initiating treatment, and a majority reported low-income status (92%). Super-users represent a small yet real subset of AOM patients. They tend to be older, report lower income, and exhibit greater visit frequency than more typical AOM users. The factors motivating AOM super-user behavior may be different from those in other medical domains, notably emergency medicine, and likely include long-term management of chronic pain and other chronic conditions. Future studies into the long-term health outcomes of AOM super-users, as well as the economic impact on other health services, are warranted.

Long-term safety and analgesic efficacy of buprenorphine buccal film in patients with moderate-to-severe chronic pain requiring around-the-clock opioids.

BackgroundThis open-label, single-arm study was conducted to evaluate the long-term safety and efficacy of a novel buprenorphine formulation, buprenorphine buccal film, in the treatment of moderate-to-severe chronic pain requiring around-the-clock opioids.MethodsThe primary purpose of this study was to evaluate the long-term safety and tolerability of buprenorphine buccal film. Five hundred and six patients who completed previous studies with buprenorphine buccal film (n=445; rollover patients) or were recruited de novo for this study (n=61) were enrolled in this study. All patients underwent a dose titration period of ≤6 weeks, during which doses of buprenorphine buccal film were adjusted to a maximum 900 µg every 12 hours, depending on tolerability and the need for rescue medication. An optimal dose was defined as the dose that the patient found satisfactory for both pain relief and tolerability, without the need for rescue medication or with ≤2 tablets of rescue medication per day. Once the optimal dose was reached, treatment was continued for ≤48 weeks. Pain intensity was measured throughout the study using a 0–10 numerical rating scale.ResultsOf 435 patients achieving an optimal dose of buprenorphine buccal film who commenced long-term treatment, 158 (36.3%) completed 48 weeks of treatment. Treatment-related adverse events occurred in 116 patients (22.9%) during the titration phase and 61 patients (14.0%) during the long-term treatment phase, and adverse events leading to discontinuation of treatment occurred in 14 (2.8%) and 14 (3.2%) patients, respectively. The most common adverse events were those typically associated with opioids, such as nausea, constipation, and headache. In both rollover and de novo patients, pain intensity scores remained constant at approximately 3–4 during long-term treatment, and the dose of buprenorphine buccal film remained unchanged in 86.2% of patients.ConclusionIn appropriate patients, buprenorphine buccal film demonstrated tolerability and efficacy in the long-term management of chronic pain.

Acupuncture and Chronic Pain Management.

According to National Institute of Health Pathways to Prevention Workshop (2014), chronic pain affects an estimated 100 million Americans, with approximately 25 million people experiencing moderate to severe chronic pain, which negatively impacts their ability to function leading to a diminished quality of life. Pain is the primary reason Americans are on disability, which adds to the economic and social burden of suffering for the nation. Chronic pain costs are estimated to be between 560 and 630 billion per year. An estimated 5 to 8 million Americans use opioids for long-term management of chronic pain, which can have deleterious effects on their lives including addiction. Recent evidence suggests that acupuncture, a treatment modality that has been used worldwide for over 2,000 years, may provide a useful pain management option for those who suffer from chronic pain. The investigation into its mechanism of action and efficacy remains elusive, but promising.

Integration of Complementary and Alternative Medicine Therapies into Primary-Care Pain Management for Opiate Reduction in a Rural Setting.

Opiates are no longer considered the best strategy for the long-term management of chronic pain. Yet, physicians have made many patients dependent on them, and these patients still request treatment. Complementary and alternative medicine (CAM) therapies have been shown to be effective, but are not widely available and are not often covered by insurance or available to the medically underserved. Group medical visits (GMVs) provided education about non-pharmacological methods for pain management and taught mindfulness techniques, movement, guided imagery, relaxation training, yoga, qigong, and t'ai chi. Forty-two patients attending GMVs for at least six months were matched prospectively with patients receiving conventional care. No one increased their dose of opiates. Seventeen people reduced their dose, and seven people stopped opiates. On a 10-point scale of pain intensity, reductions in pain ratings achieved statistical significance (p = 0.001). The average reduction was 0.19 (95% confidence interval [CI] 0.12-0.60; p = 0.01). The primary symptom improved on average by -0.42 (95% CI -0.31 to -0.93; p = 0.02) on the My Medical Outcome Profile, 2nd version. Improvement in the quality-of-life rating was statistically significant (p = 0.007) with a change of -1.42 (95% CI = -0.59 to -1.62). In conventional care, no patients reduced their opiate use, and 48.5% increased their dose over the two years of the project. GMVs that incorporated CAM therapies helped patients reduce opiate use. While some patients found other physicians to give them the opiates they desired, those who persisted in an environment of respect and acceptance significantly reduced opiate consumption compared with patients in conventional care. While resistant to CAM therapies initially, the majority of patients came to accept and to appreciate their usefulness. GMVs were useful for incorporating non-reimbursed CAM therapies into primary medical care.

Intrathecal Therapy for Cancer-Related Pain.

Objective. The increasing incidence of cancer survivorship has shifted treatment of cancer-related pain from short-term analgesia to long-term chronic pain management. As a result, alternatives to oral analgesics, such as intrathecal therapy, may be beneficial for patients with cancer-related pain. The authors review the use of intrathecal therapy in the management of cancer-related pain. Methods. The Medline database was searched for English-language articles that included “ziconotide” or “morphine” AND (“cancer” OR “malignant”) AND “intrathecal” in title or abstract. Available abstracts from scientific congresses in the areas of neuromodulation and oncology were also reviewed. Results. Intrathecal therapy provides pain relief with reduced systemic concerns in patients with cancer-related pain. Patients should undergo multidisciplinary evaluation and, in most cases, drug trialing before intrathecal pump implantation. Morphine, an opioid (µ-opioid receptor antagonist), and ziconotide, a nonopioid (selective N-type calcium channel inhibitor), are both approved for intrathecal analgesia; however, tolerance and safety concerns may deter the use of intrathecal morphine. Ziconotide has also shown efficacy for reduction of cancer-related pain; however, proper dosing and titration must be used to prevent adverse events. There is little information available on use of intrathecal therapies specifically in cancer survivors. Conclusions. Treatment of cancer-related pain has shifted toward chronic pain management strategies, especially among cancer survivors. Intrathecal therapy provides an alternate route of administration of chronic pain medications (e.g., morphine and ziconotide) for cancer patients with and without active disease, although additional research is needed to support effectiveness in cancer survivors.

Analgesic Effect of Recombinant GABAergic Cells in a Model of Peripheral Neuropathic Pain

Chronic neuropathic pain represents a clinically challenging state with a poor response to current treatment options. Long-term management of chronic pain is often associated with the development of tolerance, addiction, and other side effects, reducing the therapeutic value of treatment. Alternative strategies based on cell therapy and gene manipulation, balancing the inhibitory and excitatory events in the spinal cord, may provide sustained pain relief in the long term. Transplantation of GABAergic cells has been successfully used to enhance inhibition and to restore physiological spinal pain processing. However, since the underlying mechanism of chronic pain development involves changes in several pain-signaling pathways, it is essential to develop an approach that targets several components of pain signaling. Recombinant cell therapy offers the possibility to deliver additional analgesic substances to the restricted area in the nervous system. The current study explores the analgesic potential of genetically modified rat embryonic GABAergic cells releasing a peptidergic NMDA receptor antagonist, Serine(1)-histogranin (SHG). Overactivation of glutamate NMDA receptors contributes to the hyperexcitability of spinal neurons observed in chronic pain models. Our approach allows us to simultaneously target spinal hyperexcitability and reduced inhibitory processes. Transplantable cells were transduced by viral vectors encoding either one or six copies of SHG cDNAs. The analgesic potential of recombinant cells after their intraspinal transplantation was evaluated in a model of peripheral nerve injury. Enhanced reduction of hypersensitivity to thermal and mechanical stimuli was observed in animals treated by recombinant cells compared to the nonrecombinant group. The recombinant peptide was detected in the spinal tissue, suggesting its successful production by transplanted cells. Our results demonstrate the feasibility of using recombinant cells releasing adjunct analgesic peptides in the therapy of neuropathic pain.

Surgical Management of Pain and Infertility Secondary to Endometriosis

The management of pain and infertility secondary to endometriosis remains a challenge. Surgical management of early-stage endometriosis-associated infertility has only a mild effect with a number needed to treat of at least 12 to achieve one pregnancy. Excision of endometriomas provides the best outcome for fertility and pain; however, there is a potential to reduce the ovarian reserve. Pain relief is seen in most patients undergoing surgical management but with a high recurrence rate over time. Long-term postoperative medical suppressive therapy with oral contraceptives may have some benefit in reducing recurrence of symptoms. Hysterectomy is effective in the long-term management of chronic pain associated with endometriosis.

Long-term management of chronic pain with transdermal buprenorphine: A multicenter, open-label, follow-up study in patients from three short-term clinical trials

Transdermal buprenorphine is available in Europe for the treatment of moderate to severe chronic pain. It has been evaluated at doses of 35, 52.5, and 70 microg/h for the management of moderate to severe chronic cancer and noncancer pain in 3 randomized, double-blind, placebo-controlled trials, each of limited duration (approximately 14 days each). Long-term data are essential to determining the performance of an analgesic in the management of chronic pain. The purpose of this follow-up study was to obtain data on the efficacy and tolerability of long-term treatment with transdermal buprenorphine in cancer and noncancer patients with chronic persistent pain of moderate to severe intensity. This was an open-label, uncontrolled, follow-up study in patients from the 3 previous clinical trials who elected to continue treatment with transdermal buprenorphine 35 microg/h and sublingual buprenorphine tablets (0.2 mg) as needed for breakthrough pain. The patch was to be changed every 72 hours throughout the patient's course of pain therapy. At visits every 2 weeks for the first 4 weeks and every 4 weeks for the remainder of study participation, patients evaluated their pain relief retrospectively on a 4-point verbal rating scale. They also rated the ease of patch handling using a 3-point verbal rating scale. Patterns of dose escalation and dose stability were monitored over time. Adherence to therapy was determined based on the number of patients who complied with the dosing schedule. Adverse events were documented by type, intensity, location (systemic or local), and relationship to study medication. Two hundred thirty-nine patients were included in this follow-up study (120 women, 119 men; 100% white; mean [SD] age, 58 [11.3] years; mean weight, 70.8 [14.7] kg). One hundred thirty-four had cancer-related pain and 105 had pain of noncancerous origin. The mean duration of participation was 7.5 months, and 37 (15.5%) patients participated for >12 months. Maximum study participation was 3.4 years in cancer patients and 5.7 years in noncancer patients. One hundred eighty-eight (78.7%) patients were considered adherent to therapy. The majority (65.9%) of patients managed their pain with the patchalone or took no more than 1 additional sublingual tablet daily for breakthrough pain. At least satisfactory pain relief was reported by 215 (90.0%) patients, and the buprenorphine patch was generally well tolerated. The most common systemic adverse drug reactions were nausea (9.2%), dizziness (4.6%), vomiting (4.2%), constipation (3.8%), and tiredness (2.9%), whereas the most common local adverse drug reactions were erythema (12.1%), pruritus (10.5%), and exanthema (8.8%). Transdermal buprenorphine was generally well tolerated and effective for the long-term treatment of chronic cancer or noncancer pain in these patients who had previously received buprenorphine in 3 short-term clinical trials.

A Review of Intrathecal Fentanyl and Sufentanil for the Treatment of Chronic Pain

Intrathecal infusion of morphine using implantable pumps is an accepted practice for long-term management of chronic pain. Despite clinical benefit, development of tolerance and side-effects associated with intrathecal morphine has prompted investigators to explore alternative opioids such as the potent anilinopiperidine analogs, fentanyl, and sufentanil. Relevant preclinical and clinical literature from the MEDLINE database was used primarily for this review. In vitro, both compounds are stable in solution, but studies have not been conducted using implantable pumps under simulated use conditions (e.g., long-term stability at body temperature). Preclinical studies of limited duration have demonstrated efficacy, but safety-toxicology studies have been limited to intermittent boluses of sufentanil only. Few clinical reports on the use of intrathecal sufentanil or fentanyl for chronic pain are available. Although results confirm potency and efficacy with intrathecal administration, further studies are needed to support the long-term use of either opioid in chronic pain management.

Characterizations of Long-term Oxycodone/Acetaminophen Prescriptions in Veteran Patients

Long-term management of chronic pain with opioids may be stable over time or may be complicated by problematic dose increases, drug dependencies, and toxic effects. To determine clinical contexts in which stability or problems may occur, we examined the pharmacologic and clinical correlates of long-term prescriptions of oxycodone/acetaminophen, a commonly prescribed short-acting opioid formulation. We analyzed linked, archival outpatient pharmacy and clinical databases from the New England Veterans Integrated Service Network between January 1, 1998, and June 30, 2001. Durations, doses, and dose changes of oxycodone/acetaminophen prescriptions and concurrent use of long-acting opioids, benzodiazepines, tricyclic antidepressants, and anticonvulsants were determined. In aggregate, 2195 patients (31% with cancer diagnoses per the International Classification of Diseases, Ninth Revision, Clinical Modification) received oxycodone/acetaminophen for more than 9 months at a mean prescribed daily dose of 3.9 tablets per day (range, 0.5-13.0 tablets per day) with minimal changes in daily prescribed mean dose over time. Patients with cancer were more likely than other patients to receive concurrent long-acting opioids. For patients without cancer, a higher mean daily dose was associated with duration, older age, human immunodeficiency virus (HIV) and/or AIDS, and with prescribed benzodiazepines and long-acting opioids; concurrent benzodiazepine prescriptions were associated with anticonvulsant prescriptions and with psychogenic pain and alcohol abuse and/or dependence diagnoses. In veteran patients who received long-term oxycodone/acetaminophen prescriptions, mean daily doses were typically modest and stable, likely reflecting a selection of patients with successful, long-term management. Among patients without cancer, however, associations of higher oxycodone/acetaminophen doses with benzodiazepine prescriptions, psychogenic pain, alcohol abuse, and HIV/AIDS may portend opioid prescription management problems.

Local peripheral effects of μ-opioid receptor agonists in neuropathic pain in rats

Our study was designed to demonstrate peripheral antinociception of the μ-opioid receptor agonists: morphine (MF), [ d-Ala 2, N-Me-Phe 4, Gly 5-ol]enkephalin (DAMGO), endomorphin-1 (EM-1) and endomorphin-2 (EM-2) in Bennett's rat model of neuropathic pain. All the agonists were effective in antagonizing allodynia after their intraplantar (i.pl.) but not subcutaneous (s.c.) administration. Opioid peptides: DAMGO, EM-1 and EM-2 were more effective compared with corresponding doses of morphine (opioid alkaloid) in alleviating chronic pain. Peripheral μ-opioid receptors mediated the observed effects, as was evidenced by the i.pl. treatment with naloxone methiodide (active only at the site of injection) and by cyprodime, a selective μ-opioid receptor antagonist. These results have shown that opioid peptides are effective also after local treatment, and that their peripheral use may be of therapeutic interest in long-term management of chronic pain.

Beyond the needle: expanding the role of anesthesiologists in the management of chronic non-malignant pain.

Beyond the needle: expanding the role of anesthesiologists in the management of chronic non-malignant pain.