Real-world effectiveness and satisfaction with intravenous eptinezumab treatment in patients with chronic migraine: REVIEW, an observational, multi-site, US-based study.

BACKGROUND: Despite recent advancements in migraine treatment, some patients continue to endure significant disease burden. Due to the controlled nature of randomized trials in migraine prevention, many real-world patients with comorbidities or prior exposure to certain therapies are excluded. Capturing evidence of the effectiveness of treatment in real-world clinical settings can further shape treatment paradigms. The objective of this study was to develop a comprehensive understanding of both patients' and physicians' real-world experiences with eptinezumab for chronic migraine (CM). METHODS: REVIEW (Real-world EVidence and Insights into Experiences With eptinezumab) is an observational, multi-site (n = 4), US-based study designed to evaluate real-world experiences of patients treated with eptinezumab and their treating physicians. Patients were ≥ 18 years of age, with a diagnosis of CM, who had completed ≥ 2 consecutive eptinezumab infusion cycles (≥ 6 months of exposure). The study included a retrospective chart review, a patient survey, and a semi-structured physician interview that assessed patient and/or physician satisfaction with elements of daily living / well-being, migraine symptomology, and perspectives of the eptinezumab infusion experience. RESULTS: Of the 94 patients enrolled, 83% (78/94) were female, the mean age was 49.2 years, and the mean time since migraine diagnosis was 15.4 years. Before eptinezumab treatment, patients experienced a mean of 8 self-reported "good" days/month, which increased to 18 after treatment. Most patients took, on average, ≥ 10 days/month of prescription and/or over-the-counter medication (81% [75/93] and 66% [61/93], respectively) to treat migraine attacks before eptinezumab treatment, which dropped to 26% (24/93) and 23% (21/93) following eptinezumab treatment. Prior to receiving eptinezumab, 62% (58/93) of patients indicated being at least slightly concerned about infusions; after eptinezumab infusion, this dropped to 14% (13/93). These patient survey findings were consistent with physician responses. CONCLUSION: This real-world evidence study demonstrated high overall satisfaction with the effectiveness of eptinezumab treatment for CM among most patients and their physicians.

4. Painful diabetic polyneuropathy.

INTRODUCTION: Pain as a symptom of diabetic polyneuropathy (DPN) significantly lowers quality of life, increases mortality and is the main reason for patients with diabetes to seek medical attention. The number of people suffering from painful diabetic polyneuropathy (PDPN) has increased significantly over the past decades. METHODS: The literature on the diagnosis and treatment of diabetic polyneuropathy was retrieved and summarized. RESULTS: The etiology of PDPN is complex, with primary damage to peripheral nociceptors and altered spinal and supra-spinal modulation. To achieve better patient outcomes, the mode of diagnosis and treatment of PDPN evolves toward more precise pain-phenotyping and genotyping based on patient-specific characteristics, new diagnostic tools, and prior response to pharmacological treatments. According to the Toronto Diabetic Neuropathy Expert Group, a presumptive diagnosis of "probable PDPN" is sufficient to initiate treatment. Proper control of plasma glucose levels, and prevention of risk factors are essential in the treatment of PDPN. Mechanism-based pharmacological treatment should be initiated as early as possible. If symptomatic pharmacologic treatment fails, spinal cord stimulation (SCS) should be considered. In isolated cases, where symptomatic pharmacologic treatment and SCS are unsuccessful or cannot be used, sympathetic lumbar chain neurolysis and/or radiofrequency ablation (SLCN/SLCRF), dorsal root ganglion stimulation (DRGs) or posterior tibial nerve stimulation (PTNS) may be considered. However, it is recommended that these treatments be applied only in a study setting in a center of expertise. CONCLUSIONS: The diagnosis of PDPN evolves toward pheno-and genotyping and treatment should be mechanism-based.

The current state of training in pain medicine fellowships: An Association of Pain Program Directors (APPD) survey of program directors.

INTRODUCTION: The Accreditation Council for Graduate Medical Education (ACGME) approved the first pain medicine fellowship programs over three decades ago, designed around a pharmacological philosophy. Following that, there has been a rise in the transition of pain medicine education toward a multidisciplinary interventional model based on a tremendous surge of contemporaneous literature in these areas. This trend has created variability in clinical experience and education amongst accredited pain medicine programs with minimal literature evaluating the differences and commonalities in education and experience of different pain medicine fellowships through Program Director (PD) experiences. This study aims to gather insight from pain medicine fellowship program directors across the country to assess clinical and interventional training, providing valuable perspectives on the future of pain medicine education. METHODS: This study involved 56 PDs of ACGME-accredited pain fellowship programs in the United States. The recruitment process included three phases: advanced notification, invitation, and follow-up to maximize response rate. Participants completed a standard online questionnaire, covering various topics such as subcategory fields, online platforms for supplemental education, clinical experience, postgraduate practice success, and training adequacy. RESULTS: Surveys were completed by 39/56 (69%) standing members of the Association of Pain Program Directors (APPD). All PDs allowed fellows to participate in industry-related and professional society-related procedural workshops, with 59% encouraging these workshops. PDs emphasized the importance of integrity, professionalism, and diligence for long-term success. Fifty-four percent of PDs expressed the need for extension of fellowship training to avoid supplemental education by industry or pain/spine societies. CONCLUSION: This study highlights the challenge of providing adequate training in all Pain Medicine subtopics within a 12-month pain medicine fellowship. PDs suggest the need for additional training for fellows and discuss the importance of curriculum standardization.

Application and Clinical Value of Definitive Drug Monitoring in Pain Management and Addiction Medicine.

OBJECTIVE: To assess routine application and clinical value of definitive urine drug monitoring (UDM) for drug detection, inconsistent drug use, and prescription adherence, along with a comparison to immunoassay screening (IAS). METHODS: Direct-to-definitive UDM performance was analyzed retrospectively in 5000 patient specimens. Drug findings, medication inconsistencies, and detection sensitivity were assessed, and definitive UDM versus IAS monitoring was studied. RESULTS: Definitive testing resulted in 18,793 drug findings with 28,403 positive drug and metabolite tests. Definitive testing expanded monitoring with 11,396 drug findings that would not be tested by IAS. The opioids accounted for the highest frequency of inconsistent positive drug-use findings, at 12%. Conversely, inconsistent negative drug findings, used as an index of prescription non-adherence, were determined in 1,751 of 15,409 monitored medications and included a high frequency of antidepressants and antipsychotics inconsistencies. Direct comparison of definitive UDM and IAS showed false-positives by IAS as well as a high rate of false-negatives that would be missed using current confirmation protocols. CONCLUSIONS: Results from routine application of direct-to-definitive UDM demonstrate the clinical value of drug-use identification and the objective evaluation of inconsistencies in drug misuse and medication adherence in pain management and addiction medicine practice. Without conversion to direct-to-definitive UDM, continuing use of IAS will limit the scope of drugs being tested, will result in an indeterminate rate of false negatives and will require confirmation testing to eliminate the reporting of false-positive IAS tests. The findings in this study provide evidence-based support for recommended use of a direct-to-definitive drug testing protocol.

An Algorithmic Approach to the Physical Exam for the Pain Medicine Practitioner: A Review of the Literature with Multidisciplinary Consensus.

BACKGROUND: Increased utilization of telemedicine has created a need for supplemental pain medicine education, especially for the virtual physical assessment of the pain patient. Traditional clinical training utilizes manual and tactile approaches to the physical examination. Telemedicine limits this approach and thus alternative adaptations are necessary to acquire information needed for sound clinical judgement and development of a treatment plan. Clinical assessment of pain is often challenging given the myriad of underlying etiologies contributing to the sensory experience. The COVID-19 pandemic has led to a dramatic increase in the use of virtual and telemedicine visits, further complicating the ease of assessing patients in pain. The increased reliance on telemedicine visits requires clinicians to develop skills to obtain objective information from afar. While eliciting a comprehensive history and medication assessment are performed in a standard fashion via telemedicine, a virtual targeted physical examination is a new endeavor in our current times. In order to appropriately diagnose and treat patients not directly in front of you, a pivot in education adaptations are necessary. OBJECTIVE: To summarize best care practices in the telemedicine physical exam while presenting an algorithmic approach towards virtual assessment for the pain practitioner. DESIGN: Review of the literature and expert multidisciplinary panel opinion. SETTING: Nationally recognized academic tertiary care centers. SUBJECTS: Multidisciplinary academic experts in pain medicine. METHODS: Expert consensus opinion from the literature review. RESULTS: An algorithm for the virtual physical exam for pain physicians was created using literature review and multidisciplinary expert opinion. CONCLUSIONS: The authors here present simple, comprehensive algorithms for physical exam evaluations for the pain physician stemming from a review of the literature.

Botulinum Toxin as an Effective Treatment for Trigeminal Neuralgia in Surgical Practices.

BACKGROUND: Trigeminal neuralgia (TN) is a common cause of craniofacial pain with many medical and surgical therapies, all of which are imperfect. We examine the use of botulinum toxin type-A (BTX-A) as an intermediary approach in surgical practices. METHODS: We retrospectively identified TN patients seen by both pain neurology and neurosurgery at our center. Demographics were collected. Pain intensity was assessed using the numerical rating scale (NRS) and compared from baseline to after BTX-A treatment via paired t test. Responder status was assessed, and success of BTX-A was determined for each cohort. Doses of common medications were compared between baseline visit and the most recent BTX-A administration visit. RESULTS: Thirty-one patients underwent BTX-A therapy for TN, 24 (77%) female and 7 (23%) male. Mean age was 62.5 ± 3.1 years and 29 (94%) identified as white. When divided into cohorts according to indication, 11 (35%) failed prior TN surgery, 9 (29%) either declined surgery or were poor surgical candidates, 4 (13%) had multiple sclerosis, 4 (13%) had trigeminal neuropathic pain, and 3 (10%) had atypical TN with pain in additional dermatomes outside the trigeminal distribution. Significant reductions in NRS from baseline to following initial BTX-A treatment were seen in the declined/high risk for surgery (p = 0.004) and those who failed prior TN surgery (p = 0.035) groups. No significant variation in demographics was found between any two groups (p > 0.05 for all). Finally, there was no significant reduction in total daily dose of gabapentin, carbamazepine, oxcarbazepine, baclofen, or lamotrigine in BTX-A responders (p > 0.05 for all). DISCUSSION: Indication is an important predictor for BTX-A, with classical TN patients exhibiting the highest response rates. This research highlights the viability of BTX-A as an important tool in the arsenal of providers seeking to treat TN in a minimally invasive manner.

Progressive Response to Repeat Application of Capsaicin 179 mg (8% w/w) Cutaneous Patch in Peripheral Neuropathic Pain: Comprehensive New Analysis and Clinical Implications.

OBJECTIVE: To investigate the efficacy of repeated application of capsaicin 179 mg cutaneous patch in nonresponders to the first application. DESIGN: Post hoc, as-treated analysis of two prospective trials (STRIDE and PACE) with 52-week follow-up. BLINDING: Open-label. SETTING: Multicenter clinical trial. SUBJECTS: STRIDE: nondiabetic neuropathic pain; PACE: painful diabetic peripheral neuropathy. METHODS: Patients were divided according to number of applications needed before attainment of a ≥30% reduction in average pain intensity (question 5 of the Brief Pain Inventory [BPI-Q5]). We assessed the change from baseline in average pain intensity (BPI-Q5), mean "interference with sleep" score, Patient Global Impression of Change, quality of life (QOL) via the EuroQol 5-dimension, and Self-Assessment of Treatment. RESULTS: In STRIDE and PACE, respectively, n = 306 and n = 313 received the capsaicin patch; n = 60 and n = 96 had a response after the first application, n = 33 and n = 68 after the second, and n = 11 and n = 43 after the third. Among patients without a ≥30% reduction in pain intensity at 3 months, in STRIDE and PACE, respectively, 23.3% and 28.1% achieved a ≥30% reduction at 6 months, increasing to 33.9% and 45.7% at 12 months. Similar results were obtained when a decrease of ≥50% was used as the responder definition. Progressive improvements in pain intensity in slower responders reached levels similar to those in early responders at month 12 and were accompanied by improvements in sleep, QOL, and patient satisfaction. CONCLUSIONS: Although some patients with peripheral neuropathic pain experience rapid improvements with a single treatment of capsaicin 179 mg patch, some may require two or three treatments before an initial response is observed. Similar benefits for pain, sleep, and QOL can be achieved in early and late responders.

Long-term Safety and Tolerability of NKTR-181 in Patients with Moderate to Severe Chronic Low Back Pain or Chronic Noncancer Pain: A Phase 3 Multicenter, Open-Label, 52-Week Study (SUMMIT-08 LTS).

OBJECTIVE: To evaluate the long-term safety of NKTR-181, a novel mu-opioid receptor agonist that may have reduced human abuse potential, in patients with moderate to severe chronic low back pain (CLBP) or other chronic noncancer pain (CNP). DESIGN: Uncontrolled, multicenter, open-label, long-term study of NKTR-181 comprised of three periods: screening (≤21 days), treatment (52 weeks), and safety follow-up (∼14 days after the last dose of NKTR-181). SETTING: Multicenter, long-term clinical research study. METHODS: NKTR-181 administered at doses of 100-600 mg twice daily (BID) was evaluated in opioid-naïve and opioid-experienced patients. Patients were enrolled de novo or following completion of the randomized, placebo-controlled phase 3 efficacy study (SUMMIT-07). Safety assessments included adverse event documentation, measurements of opioid withdrawal, and clinical laboratory tests. Effectiveness was assessed using the modified Brief Pain Inventory Short Form (mBPI-SF). RESULTS: The study enrolled 638 patients. The most frequently reported treatment-emergent adverse events (TEAEs) were constipation (26%) and nausea (12%). Serious TEAEs, reported in 5% of patients, were deemed by investigators to be unrelated to NKTR-181. There were no deaths or reported cases of respiratory depression. A sustained reduction in mBPI-SF pain intensity and pain interference from baseline to study termination was observed throughout treatment. Only 2% of patients discontinued NKTR-181 due to lack of efficacy, and 11% discontinued due to treatment-related AEs. NKTR-181 doses of up to 600 mg BID were generally well tolerated, and patients experienced low rates of opioid-related adverse events. CONCLUSIONS: The study results support the premise that NKTR-181 is a safe and effective option for patients with moderate to severe CLBP or CNP.

Small Fiber Polyneuropathy Is Prevalent in Patients Experiencing Complex Chronic Pelvic Pain.

OBJECTIVE: To demonstrate the prevalence of small fiber polyneuropathy (SFPN) in patients with refractory chronic pelvic pain (CPP). DESIGN: Retrospective study of prospective database. SUBJECTS: Participants were complex CPP patients recruited from subspecity referral clinics defined as those who were refractory to initial treatment and/or exhibited comorbid pain syndromes at initial presentation. METHODS: Comprehensive treatment history for CPP was obtained, and participants referred as above; 3-mm punch biopsies were obtained of the lower extremity and sent to diagnostic reference labs to evaluate for SFPN. The reported lab sensitivity and specificity for SFPN are 78-92% and 65-90%, respectively. RESULTS: Twenty-five of 39 patients (64%) were positive for SFPN. Comorbid conditions noted in our population included gastroesophageal reflux disease (46%), migraine (38%), irritable bowel syndrome (33%), lower back pain (33%), fibromyalgia (38%), endometriosis (15%), interstitial cystitis (18%), vulvodynia (5%), and other chronic pain syndromes (36%). CONCLUSIONS: The prevalence of SFPN in our specialty referral patients with complex CPP is remarkably high vs published general population prevalence data (53/100,000). Identification of SFPN in this complex population shifts the focus from undefined syndromes to symptom complexes with linked potentially treatable mechanisms (e.g., SFPN, central sensitization). Most CPP patients with SFPN are undiagnosed. Considering the diagnosis may expand treatment options beyond conventional or so-called adjuvant analgesics. Treatment may expand to therapies such as IV lidocaine, IVIG, or other immunomodulatory options. In addition, the value to the patient of receiving a diagnosis for a multisystem or refractory pain syndrome, often attributed to negative psychologic factors, cannot be underestimated. Identifying SFPN should be contemplated in CPP patients who present with multisystem pain or who have not responded to initial evaluation and management.

Challenges with Implementing the Centers for Disease Control and Prevention Opioid Guideline: A Consensus Panel Report.

BACKGROUND: A national crisis of opioid-related morbidity, mortality, and misuse has led to initiatives to address the appropriate role of opioids to treat pain. Deployment of a guideline from the Centers for Disease Control and Prevention to reduce the risks of opioid therapy has raised substantial clinical and public policy challenges. The agency anticipated implementation challenges and committed to reevaluating the guideline for intended and unintended effects on clinician and patient outcomes. OBSERVATIONS: A multidisciplinary expert panel met to review the influence of the core recommendations of the guideline on pain management practices, principally regarding the estimated 5 to 8 million Americans with chronic pain currently on opioids. The panel identified implementation challenges, including application of dosage ceilings and prescription duration guidance, failure to appreciate the importance of patient involvement in decisions to taper or discontinue opioids, barriers to diagnosis and treatment of opioid use disorder, and impeded access to recommended comprehensive, multimodal pain care. Furthermore, policy-making and regulatory bodies may misapply guideline recommendations without flexibility and, sometimes, without full awareness of what the guideline contains. CONCLUSIONS AND RELEVANCE: The panel largely supported the guideline, endorsing its focal points of safety and comprehensive assessment and monitoring. To mitigate clinical and policy challenges identified with implementing the guideline, the panel discussed areas where viewpoints diverged and arrived at consensus proposals. The target audience includes the leaders and institutions that create policy and influence guideline implementation to include regulatory agencies, legislators, public and private payers, and health care systems.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Perioperative Management of Patients on Preoperative Opioid Therapy.

Enhanced recovery pathways have quickly become part of the standard of care for patients undergoing elective surgery, especially in North America and Europe. One of the central tenets of this multidisciplinary approach is the use of multimodal analgesia with opioid-sparing and even opioid-free anesthesia and analgesia. However, the current state is a historically high use of opioids for both appropriate and inappropriate reasons, and patients with chronic opioid use before their surgery represent a common, often difficult-to-manage population for the enhanced recovery providers and health care team at large. Furthermore, limited evidence and few proven successful protocols exist to guide providers caring for these at-risk patients throughout their elective surgical experience. Therefore, the fourth Perioperative Quality Initiative brought together an international team of multidisciplinary experts, including anesthesiologists, nurse anesthetists, surgeons, pain specialists, neurologists, nurses, and other experts with the objective of providing consensus recommendations. Specifically, the goal of this consensus document is to minimize opioid-related complications by providing expert-based consensus recommendations that reflect the strength of the medical evidence regarding: (1) the definition, categorization, and risk stratification of patients receiving opioids before surgery; (2) optimal perioperative treatment strategies for patients receiving preoperative opioids; and (3) optimal discharge and continuity of care management practices for patients receiving opioids preoperatively. The overarching theme of this document is to provide health care providers with guidance to reduce potentially avoidable opioid-related complications including opioid dependence (both physical and behavioral), disability, and death. Enhanced recovery programs attempt to incorporate best practices into pathways of care. By presenting the available evidence for perioperative management of patients on opioids, this consensus panel hopes to encourage further development of pathways specific to this high-risk group to mitigate the often unintentional iatrogenic and untoward effects of opioids and to improve perioperative outcomes.

Rational Urine Drug Monitoring in Patients Receiving Opioids for Chronic Pain: Consensus Recommendations.

Objective: To develop consensus recommendations on urine drug monitoring (UDM) in patients with chronic pain who are prescribed opioids. Methods: An interdisciplinary group of clinicians with expertise in pain, substance use disorders, and primary care conducted virtual meetings to review relevant literature and existing guidelines and share their clinical experience in UDM before reaching consensus recommendations. Results: Definitive (e.g., chromatography-based) testing is recommended as most clinically appropriate for UDM because of its accuracy; however, institutional or payer policies may require initial use of presumptive testing (i.e., immunoassay). The rational choice of substances to analyze for UDM involves considerations that are specific to each patient and related to illicit drug availability. Appropriate opioid risk stratification is based on patient history (especially psychiatric conditions or history of opioid or substance use disorder), prescription drug monitoring program data, results from validated risk assessment tools, and previous UDM. Urine drug monitoring is suggested to be performed at baseline for most patients prescribed opioids for chronic pain and at least annually for those at low risk, two or more times per year for those at moderate risk, and three or more times per year for those at high risk. Additional UDM should be performed as needed on the basis of clinical judgment. Conclusions: Although evidence on the efficacy of UDM in preventing opioid use disorder, overdose, and diversion is limited, UDM is recommended by the panel as part of ongoing comprehensive risk monitoring in patients prescribed opioids for chronic pain.

Assessment of Patient-Reported Outcome Instruments to Assess Chronic Low Back Pain.

Objective: To identify patient-reported outcome (PRO) instruments that assess chronic low back pain (cLBP) symptoms (specifically pain qualities) and/or impacts for potential use in cLBP clinical trials to demonstrate treatment benefit and support labeling claims. Design: Literature review of existing PRO measures. Methods: Publications detailing existing PRO measures for cLBP were identified, reviewed, and summarized. As recommended by the US Food & Drug Administration (FDA) PRO development guidance, standard measurement characteristics were reviewed, including development history, psychometric properties (validity and reliability), ability to detect change, and interpretation of observed changes. Results: Thirteen instruments were selected and reviewed: Low Back Pain Bothersomeness Scale, Neuropathic Pain Symptom Inventory, PainDETECT, Pain Quality Assessment Scale Revised, Revised Short Form McGill Pain Questionnaire, Low Back Pain Impact Questionnaire, Oswestry Disability Index, Pain Disability Index, Roland-Morris Disability Questionnaire, Brief Pain Inventory and Brief Pain Inventory Short Form, Musculoskeletal Outcomes Data Evaluation and Management System Spine Module, Orebro Musculoskeletal Pain Questionnaire, and the West Haven-Yale Multidimensional Pain Inventory Interference Scale. The instruments varied in the aspects of pain and/or impacts that they assessed, and none of the instruments fulfilled all criteria for use in clinical trials to support labeling claims based on recommendations outlined in the FDA PRO guidance. Conclusions: There is an unmet need for a validated PRO instrument to evaluate cLBP-related symptoms and impacts for use in clinical trials.

Use of Low Dose Ziconotide as First-Line Intrathecal Monotherapy.

BACKGROUND: Ziconotide use in intrathecal drug therapy (IDT) has been limited by dosing related side effects. We examine our experience with ziconotide as a first line IDT monotherapy in patients with chronic pain and present our low and slow dosing algorithm aimed at reducing these patient experienced side effects while adequately managing pain. METHODS: We retrospectively reviewed demographics, dosing, and outcomes of 15 consecutive patients with complete three-month data sets implanted with intrathecal pain pumps more than three years utilizing ziconotide as a first-line monotherapy. RESULTS: Ziconotide response was assessed at visit 5 (69 ± 10 days) and responders were characterized by having 30% or greater improvement in numerical rating scale scores (n = 7), or activities of daily living (ADL) (n = 7). Eight of our patients had a response in at least one measure (53%). In our eight responders, NRS score decreased from 8.4 ± 0.7 at baseline (consult visit) to 2.4 ± 1.0 at 2.6 months and 4.0 ± 1.3 at most recent follow-up, mean of 12.9 months after implant. We noted that our responders tended to have neuropathic pain with an objective etiology. Initial dosing in 12 patients was 1.2 mcg/day (range for the other three patients was 0.6-1.4). Following initial dosing, visits were at 2-4 week intervals with mean titration doses between 1.1 and 2.8 mcg/day. Slight dizziness in two patients and transient urinary retention in one patient occurred, all resolving with dose reduction. No patients had discontinued use at three-month follow-up. DISCUSSION: We present our experience with low and slow ziconotide IDT as a first-line monotherapy, which showed no side effects resulting in discontinuation of the medication at three-month follow-up. Using a conservative dosing strategy, we were able to effectively treat 53% of patients.

SoluMatrix® Diclofenac: Sustained Opioid-Sparing Effects in a Phase 3 Study in Patients with Postoperative Pain.

OBJECTIVES: To evaluate opioid rescue medication usage and the opioid-sparing effect of low-dose SoluMatrix® diclofenac developed using SoluMatrix Fine Particle Technology™ in a phase 3 study in patients experiencing pain following bunionectomy surgery. DESIGN: Multicenter, randomized, double-blind, parallel-group study (NCT01462435). SETTING: Four clinical research centers in the United States. SUBJECTS: Four hundred twenty-eight patients aged 18 to 65 years who experienced moderate-to-severe pain following bunionectomy surgery. METHODS: Patients were randomized to receive low-dose SoluMatrix diclofenac 35 mg or 18 mg capsules three times daily (35-mg group or 18-mg group), celecoxib 400 mg loading dose followed by 200-mg capsules twice daily (celecoxib 200-mg group), or placebo capsules postsurgery. Patients were permitted to receive opioid-containing rescue medication as needed. RESULTS: Significantly fewer patients who received SoluMatrix diclofenac 35 mg or 18 mg or celecoxib required rescue medication during 0-24 h and >24-48 h postsurgery compared with placebo. Patients in the SoluMatrix diclofenac 35 mg or 18 mg groups or in the celecoxib group used fewer mean rescue medication tablets over 0-24 h and >24-48 h compared with placebo-treated patients. Patients in the SoluMatrix diclofenac 35 mg and 18 mg groups and in the celecoxib group also required rescue medication at later times and at slower rates compared with placebo-treated patients. No serious adverse effects occurred in patients receiving SoluMatrix diclofenac. CONCLUSIONS: SoluMatrix diclofenac at two dosage strengths demonstrated an opioid-sparing effect postoperatively in this phase 3 study. SUMMARY: The opioid-sparing effect following low-dose SoluMatrix diclofenac (35 mg or 18 mg three times daily) administration was evaluated in patients experiencing pain following bunionectomy. Significantly fewer patients receiving SoluMatrix diclofenac or celecoxib (400 mg loading, 200 mg twice daily) required rescue medication during 0-24 h and >24-48 h following bunionectomy compared with placebo. No serious adverse events were reported among patients who received SoluMatrix diclofenac. SoluMatrix diclofenac may reduce opioid usage in the postoperative setting in patients with acute pain.

Pregabalin Improves Pain Scores in Patients with Fibromyalgia Irrespective of Comorbid Osteoarthritis.

OBJECTIVE: Fibromyalgia (FM) is a chronic pain disorder with patients frequently suffering from comorbid conditions, including osteoarthritis (OA). Data on how FM patients with comorbid OA respond to recommended therapies (such as pregabalin) could help their treatment. DESIGN: This was a pooled exploratory analysis of three randomized placebo-controlled clinical trials of pregabalin in FM patients to assess the impact of comorbid OA on the response to pregabalin. METHODS: Patients were divided into those with and without comorbid OA. Difference in change in least squares (LS) mean pain score at endpoint (assessed by 0-10 numeric rating scale, controlled for baseline pain score) with pregabalin (300 mg/day and 450 mg/day) vs placebo was assessed. Changes in Patient Global Impression of Change (PGIC) responders and Fibromyalgia Impact Questionnaire (FIQ) total score were also assessed. RESULTS: There were 1665 patients in the analysis set (558, placebo; 552, pregabalin 300 mg/day; 555, pregabalin 450 mg/day), including 296 with comorbid OA. Pregabalin 450 mg/day significantly improved the LS mean (95% confidence interval) difference in pain score vs placebo in patients with (0.99 [0.44, 1.55], P < 0.001), and without (0.64 [0.39, 0.89], P < 0.001) OA. Improvements with pregabalin 300 mg/day with (0.31 [-0.25, 0.86], P = 0.276) and without (0.51 [0.25, 0.76], P < 0.001) OA were not consistently significant. Improvements in PGIC and FIQ total score were observed in patients with and without comorbid OA. CONCLUSIONS: FM patients with or without comorbid OA respond to treatment with pregabalin 450mg/day with significant improvements in pain intensity scores. These data could provide guidance to healthcare professionals treating these patients.

Post-herpetic Neuralgia: a Review.

Post-herpetic neuralgia (PHN) is a chronic neuropathic pain condition that persists 3 months or more following an outbreak of shingles. Shingles, also known as acute herpes zoster, is associated with the reactivation of the dormant varicella zoster virus in an individual who has experienced chicken pox. PHN is associated with persistent and often refractory neuropathic pain. Patients may experience multiple types of pain including a constant deep, aching, or burning pain; a paroxysmal, lancinating pain; hyperalgesia (painful stimuli are more painful than expected); and allodynia (pain associated with typically non-painful stimuli). The pharmacological treatment of PHN may include a variety of medications including alpha-2 delta ligands (gabapentin and pregabalin), other anticonvulsants (carbamazepine), tricyclic antidepressants (amitriptyline, nortriptyline, doxepin), topical analgesics (5 % lidocaine patch, capsaicin) tramadol, or other opioids. The considerable side effect profiles of the commonly used oral medications often limit their practical use, and a combination of both topical and systemic agents may be required for optimal outcomes. Physicians and other treatment providers must tailor treatment based on the response of individual patients.

The Impact of Spinal Cord Stimulation on Sleep Patterns.

BACKGROUND: Studies of chronic pain show sleep disturbances to be a prevalent symptom in 50-88% of patients and studies show improved pain to correspond with improved sleep. The impact of spinal cord stimulation (SCS) on sleep in failed back surgery syndrome, complex regional pain syndrome, and neuropathic pain patients has not been studied prospectively. OBJECTIVES: We prospectively assess the impact of SCS on sleep quality using the Insomnia Severity Index (ISI) and Epworth Sleepiness Scale (ESS). Further we examine the correlations between sleep and pain. METHODS: Patients who underwent permanent SCS implantation completed six validated questionnaires to compare sleep patterns, pain intensity, and quality of life at baseline and six months postoperatively. Results were analyzed via paired samples t-tests and bivariate analysis. RESULTS: Data from 27 patients were collected. We saw a significant decrease in ISI scores (n = 23, t(df)=2.9(22), p = 0.008), and noted a trend in the percentage improvement between ISI and ESS (n = 12, t(df)=2.0(10), p = 0.078). We did not see any significant improvement in ESS. However, improvements in insomnia correlated with pain intensity as measured through visual analog scale score and McGill Pain Questionnaire (R = 0.546, p = 0.007 and R = 0.559, p = 0.006, respectively). DISCUSSION: We demonstrate that insomnia scores on ISI improve with SCS at six-month follow-up. Further, we find that improvements in pain correlate with these ISI improvements.

The Effects of Mechanical and Thermal Stimuli on Local Field Potentials and Single Unit Activity in Parkinson's Disease Patients.

BACKGROUND: Chronic pain is a major, debilitating symptom of Parkinson's disease (PD). Although, deep brain stimulation (DBS) has been shown to improve pain outcomes, the mechanisms underlying this phenomenon are unclear. Microelectrode recording allows us to measure both local field potentials (LFPs) and single neuronal unit activity (SUA). OBJECTIVE: In this study, we examined how single unit and LFP oscillatory activity in the basal ganglia are impacted by mechanical and thermal sensory stimuli and explored their role in pain modulation. METHODS: We assessed changes in LFPs and SUAs in the subthalamic nucleus (STN), globus pallidus interna (Gpi), and globus pallidus externa (Gpe) following exposure with mechanical or thermal stimuli. Sensory thresholds were determined pre-operatively using quantitative sensory testing. Based on these data, patients were exposed to innocuous and noxious mechanical, pressure, and thermal stimuli at individualized thresholds. RESULTS: In the STN, LFP alpha oscillatory activity and SUA increased in response to innocuous mechanical stimuli; SUA further increased in response to noxious mechanical, noxious pressure, and noxious thermal stimuli (p < 0.05). In the Gpe, LFP low betaactivity and SUA increased with noxious thermal stimuli; SUA also increased in response to innocuous thermal stimuli (p < 0.05). In the Gpi, innocuous thermal stimuli increased LFP gammaactivity; noxious pressure stimuli decreased low betaactivity; SUA increased in response to noxious thermal stimuli (p < 0.05). DISCUSSION: Our study is the first to demonstrate that mechanical and thermal stimuli alter basal ganglia LFPs and SUAs in PD. While STN SUA increases nearly uniformly to all sensory stimuli, SUA in the pallidal nuclei respond solely to thermal stimuli. Similarly, thermal stimuli yield increases in pallidal LFP activity, but not STN activity. We speculate that DBS may provide analgesia through suppression of stimuli-specific changes in basal ganglia activity, supporting a role for these nuclei in sensory and pain processing circuits.