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.

Clinical Uses of Intrathecal Therapy and Its Placement in the Pain Care Algorithm.

Intrathecal drug delivery is an effective treatment option for patients with severe chronic pain who have not obtained adequate analgesia from more conservative therapies (eg, physical therapy, systemic opioids, nonsteroidal anti-inflammatory drugs, antidepressants, and anticonvulsants). This review focuses on, but is not limited to, the 2 agents currently approved by the U.S. Food and Drug Administration for intrathecal analgesia: preservative-free morphine and ziconotide (a nonopioid, selective N-type calcium channel blocker). We describe the appropriate use of intrathecal therapy in the management of severe chronic pain, based on current best practices. Topics addressed here include patient selection, trialing, dosing and titration, adverse event profiles, long-term management, intrathecal therapy for cancer-related pain, and the placement of intrathecal therapy in the pain care algorithm. In appropriately selected patients with chronic pain, intrathecal therapy can provide substantial pain relief with improved functioning and quality of life. Successful long-term management requires ongoing patient monitoring for changes in efficacy and the occurrence of adverse events, with subsequent changes in intrathecal dosing and titration, the addition of adjuvant intrathecal agents, and the use of concomitant oral medications to address side effects, as needed. Based on an infrequent but clinically concerning risk of overdose, granuloma, and other opioid-induced complications, nonopioid therapy with ziconotide may be preferred as a first-line intrathecal therapy in patients without a history of psychosis or allergy.

The Metastatic Spine Disease Multidisciplinary Working Group Algorithms.

The Metastatic Spine Disease Multidisciplinary Working Group consists of medical and radiation oncologists, surgeons, and interventional radiologists from multiple comprehensive cancer centers who have developed evidence- and expert opinion-based algorithms for managing metastatic spine disease. The purpose of these algorithms is to facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding the use of available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation. This consensus document details the evidence supporting the Working Group algorithms and includes illustrative cases to demonstrate how the algorithms may be applied.

Evidence-based pain medicine for primary care physicians.

The last several decades have seen a marked increase in both the recognition and treatment of chronic pain. Unfortunately, patients frequently misunderstand both the nature of pain and the best practices for its treatment. Because primary care physicians treat the majority of chronic pain, they are ideally situated to provide evidence-based pain care. The majority of the medical evidence supports a biopsychosocial model of pain that integrates physical, emotional, social, and cultural variables. The goal of this primer is to assist primary care physicians in their understanding of pain, evaluation of the chronic pain patient, and ability to direct evidence-based care. This article will discuss the role of physical rehabilitation, pain psychology, pharmacotherapy, and procedural interventions in the treatment of chronic pain. Given the current epidemic of drug-related deaths, particular emphasis is placed on the alternatives to opioid therapy. Unfortunately, death is not the only significant complication from opioid therapy, and this article discusses many of the most common side effects. This article provides general guidelines on the most appropriate utilization of opioids with emphasis on the recent Centers for Disease Control and Prevention guidelines, risk stratification, and patient monitoring. Finally, the article concludes with the critical role that a pain medicine specialist can play in the management of patients with chronic pain.

Management of vertebral fragility fractures: a clinical care pathway developed by a multispecialty panel using the RAND/UCLA Appropriateness Method.

BACKGROUND CONTEXT: Vertebral fragility fractures (VFFs), mostly due to osteoporosis, are very common and are associated with significant morbidity and mortality. There is a lack of consensus on the appropriate management of patients with or suspected of having a VFF. PURPOSE: This work aimed at developing a comprehensive clinical care pathway (CCP) for VFF. STUDY DESIGN/SETTING: The RAND/UCLA Appropriateness Method was used to develop patient-specific recommendations for the various components of the CCP. The study included two individual rating rounds and two plenary discussion sessions. METHODS: A multispecialty expert panel (orthopedic and neurosurgeons, interventional [neuro]radiologists and pain specialists) assessed the importance of 20 signs and symptoms for the suspicion of VFF, the relevance of 5 diagnostic procedures, the appropriateness of vertebral augmentation versus nonsurgical management for 576 clinical scenarios, and the adequacy of 6 aspects of follow-up care. RESULTS: The panel identified 10 signs and symptoms believed to be relatively specific for VFF. In patients suspected of VFF, advanced imaging was considered highly desirable, with MRI being the preferred diagnostic modality. Vertebral augmentation was considered appropriate in patients with positive findings on advanced imaging and in whom symptoms had worsened and in patients with 2 to 4 unfavorable conditions (eg, progression of height loss and severe impact on functioning), dependent on their relative weight. Time since fracture was considered less relevant for treatment choice. Follow-up should include evaluation of bone mineral density and treatment of osteoporosis. CONCLUSIONS: Using the RAND/UCLA Appropriateness Method, a multispecialty expert panel established a comprehensive CCP for the management of VFF. The CCP may be helpful to support decision-making in daily clinical practice and to improve quality of care.

Complications after intrathecal drug delivery due to the underlying malignancy in two patients with intractable cancer pain.

Intrathecal drug delivery is a mode of analgesic delivery that can be considered in those experiencing both refractory pain and excessive side effects from opioid and adjuvant analgesic use. Delivery of analgesic agents directly to the cerebral spinal fluid allows binding of the drug to receptors at the spinal level. Therefore, a reduced analgesic dosage can be afforded, resulting in reduction of drug side effects due to decreased systemic absorption. Drug delivery into the intrathecal space provides this benefit, yet it does not eliminate the possibility of drug side effects or risks of complications. Complications from this route of administration may be seen in the perioperative period or beyond, including infection, inflammatory mass, bleeding, and catheter or pump dysfunction, among others. This may manifest as new/worsening pain or as a neurologic deficit, such as a sensorimotor change and bladder/bowel dysfunction. Urgent evaluation with a detailed physical examination, device interrogation, and other workup including imaging is called for if symptoms suspicious for device-related problems arise. For the cancer pain patient, the underlying malignancy should also be considered as a potential cause for these new symptoms after intrathecal system implantation. We present 2 such cases of complications in the cancer pain patient after intrathecal drug delivery due to progression of the underlying malignant process rather than to surgical or device-related problems. The first patient had a history of metastatic osteosarcoma who, shortly after undergoing an intrathecal drug delivery trial with external pump, presented with new symptoms of both pain and neurologic changes. The second patient with a history of chondrosarcoma developed new symptoms of pain and sensorimotor change several days after intrathecal drug delivery system implantation.

Persistent chemoneuropathy in patients receiving the plant alkaloids paclitaxel and vincristine.

PURPOSE: Chemoneuropathy remains a painful, burdensome complication of cancer treatment for patients receiving a range of chemotherapeutics, yet the cause and persistence of this condition are not fully documented. This study was designed to quantify the longevity of and contributions to neuropathy following treatment with the plant alkaloids paclitaxel and vincristine. METHODS: Quantitative sensory testing was conducted approximately 18 months apart on 14 patients, seven of which had been treated with paclitaxel and seven with vincristine and compared to data from 18 healthy control subjects. In addition, skin biopsies were obtained to investigate changes in the density of Meissner's corpuscles and epidermal nerve fibers (ENFs), the loss of which is thought to contribute to multiple forms of neuropathy. RESULTS: Impairments in motor skills, as measured by a grooved peg-board, were found. Deficits in touch detection were observed using von Frey monofilaments, as were changes in sharpness detection using a weighted needle device. Using a Peltier device, warmth and heat detection were impaired. These deficits were consistent across time. Remarkably, the average length of time patients reported painful neuropathy was over four and a half years. Skin biopsies were found to be deficient in Meissner's corpuscles and ENFs. CONCLUSIONS: The combination of widespread deficits in sensory testing and decreases in skin innervation for cancer patients receiving paclitaxel or vincristine document a persistent polyneuropathy which severely impacts these patients. Decreases in Meissner's corpuscles and ENFs indicate a possible mechanism for the neuropathy.

A systematic review of randomized trials on the effectiveness of opioids for cancer pain.

BACKGROUND: In all recommended guidelines put forth for the treatment of cancer pain, opioids continue to be an important part of a physician's armamentarium. Though opioids are used regularly for cancer pain, there is a paucity of literature proving efficacy for long-term use. Cancer is no longer considered a "terminal disease"; 50% to 65% of patients survive for at least 2 years, and there are about 12 million cancer survivors in the United States. There is a concern about side effects, tolerance, abuse and addiction with long-term opioid use and a need to evaluate the effectiveness of opioids for cancer pain. OBJECTIVE: The objective of this systematic review was to look at the effectiveness of opioids for cancer pain. STUDY DESIGN: A systematic review of randomized trials of opioids for cancer pain. METHODS: A comprehensive review of the current literature for randomized controlled trials (RCTs) of opioids for cancer pain was done. The literature search was done using PubMed, EMBASE, Cochrane library, clinical trials, national clearing house, Web of Science, previous narrative systematic reviews, and cross references. The studies were assessed using the modified Cochrane and Jadad criteria. Analysis of evidence was done utilizing the modified quality of evidence developed by United States Preventive Services Task Force (USPSTF). OUTCOME MEASURES: Pain relief was the primary outcome measure. Secondary outcome measures are quality of life (QoL) and side effects including tolerance and addiction. RESULTS: The level of evidence for pain relief based on the USPSTF criteria was fair for transdermal fentanyl and poor for morphine, tramadol, oxycodone, methadone, and codeine. LIMITATIONS: Randomized trials in a cancer setting are difficult to perform and justify. There is a paucity of long-term trials and this review included a follow-up period of only 4 weeks. CONCLUSION: This systematic review of RCTs of opioids for cancer pain showed fair evidence for the efficacy of transdermal fentanyl and poor evidence for morphine, tramadol, oxycodone, methadone, and codeine.

American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part I--evidence assessment.

BACKGROUND: Opioid abuse has continued to increase at an alarming rate since the 1990 s. As documented by different medical specialties, medical boards, advocacy groups, and the Drug Enforcement Administration, available evidence suggests a wide variance in chronic opioid therapy of 90 days or longer in chronic non-cancer pain. Part 1 describes evidence assessment. OBJECTIVES: The objectives of opioid guidelines as issued by the American Society of Interventional Pain Physicians (ASIPP) are to provide guidance for the use of opioids for the treatment of chronic non-cancer pain, to produce consistency in the application of an opioid philosophy among the many diverse groups involved, to improve the treatment of chronic non-cancer pain, and to reduce the incidence of abuse and drug diversion. The focus of these guidelines is to curtail the abuse of opioids without jeopardizing non-cancer pain management with opioids. RESULTS: 1) There is good evidence that non-medical use of opioids is extensive; one-third of chronic pain patients may not use prescribed opioids as prescribed or may abuse them, and illicit drug use is significantly higher in these patients. 2) There is good evidence that opioid prescriptions are increasing rapidly, as the majority of prescriptions are from non-pain physicians, many patients are on long-acting opioids, and many patients are provided with combinations of long-acting and short-acting opioids. 3) There is good evidence that the increased supply of opioids, use of high dose opioids, doctor shoppers, and patients with multiple comorbid factors contribute to the majority of the fatalities. 4) There is fair evidence that long-acting opioids and a combination of long-acting and short-acting opioids contribute to increasing fatalities and that even low-doses of 40 mg or 50 mg of daily morphine equivalent doses may be responsible for emergency room admissions with overdoses and deaths. 5) There is good evidence that approximately 60% of fatalities originate from opioids prescribed within the guidelines, with approximately 40% of fatalities occurring in 10% of drug abusers. 6) The short-term effectiveness of opioids is fair, whereas the long-term effectiveness of opioids is limited due to a lack of long-term (> 3 months) high quality studies, with fair evidence with no significant difference between long-acting and short-acting opioids. 7) Among the individual drugs, most opioids have fair evidence for short-term and limited evidence for long-term due to a lack of quality studies. 8) The evidence for the effectiveness and safety of chronic opioid therapy in the elderly for chronic non-cancer pain is fair for short-term and limited for long-term due to lack of high quality studies; limited in children and adolescents and patients with comorbid psychological disorders due to lack of quality studies; and the evidence is poor in pregnant women. 9) There is limited evidence for reliability and accuracy of screening tests for opioid abuse due to lack of high quality studies. 10) There is fair evidence to support the identification of patients who are non-compliant or abusing prescription drugs or illicit drugs through urine drug testing and prescription drug monitoring programs, both of which can reduce prescription drug abuse or doctor shopping. DISCLAIMER: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

American Society of Interventional Pain Physicians (ASIPP) guidelines for responsible opioid prescribing in chronic non-cancer pain: Part 2--guidance.

RESULTS: Part 2 of the guidelines on responsible opioid prescribing provides the following recommendations for initiating and maintaining chronic opioid therapy of 90 days or longer. 1. A) Comprehensive assessment and documentation is recommended before initiating opioid therapy, including documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history. ( EVIDENCE: good) B) Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse. ( EVIDENCE: limited) C) Prescription monitoring programs must be implemented, as they provide data on patterns of prescription usage, reduce prescription drug abuse or doctor shopping. ( EVIDENCE: good to fair) D) Urine drug testing (UDT) must be implemented from initiation along with subsequent adherence monitoring to decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy. ( EVIDENCE: good) 2. A) Establish appropriate physical diagnosis and psychological diagnosis if available prior to initiating opioid therapy. ( EVIDENCE: good) B) Caution must be exercised in ordering various imaging and other evaluations, interpretation and communication with the patient, to avoid increased fear, activity restriction, requests for increased opioids, and maladaptive behaviors. ( EVIDENCE: good) C) Stratify patients into one of the 3 risk categories - low, medium, or high risk. D) A pain management consultation, may assist non-pain physicians, if high-dose opioid therapy is utilized. ( EVIDENCE: fair) 3. Essential to establish medical necessity prior to initiation or maintenance of opioid therapy. ( EVIDENCE: good) 4. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. ( EVIDENCE: good) 5. A) Long-acting opioids in high doses are recommended only in specific circumstances with severe intractable pain that is not amenable to short-acting or moderate doses of long-acting opioids, as there is no significant difference between long-acting and short-acting opioids for their effectiveness or adverse effects. ( EVIDENCE: fair) B) The relative and absolute contraindications to opioid use in chronic non-cancer pain must be evaluated including respiratory instability, acute psychiatric instability, uncontrolled suicide risk, active or history of alcohol or substance abuse, confirmed allergy to opioid agents, coadministration of drugs capable of inducing life-limiting drug interaction, concomitant use of benzodiazepines, active diversion of controlled substances, and concomitant use of heavy doses of central nervous system depressants. ( EVIDENCE: fair to limited) 6. A robust agreement which is followed by all parties is essential in initiating and maintaining opioid therapy as such agreements reduce overuse, misuse, abuse, and diversion. ( EVIDENCE: fair) 7. A) Once medical necessity is established, opioid therapy may be initiated with low doses and short-acting drugs with appropriate monitoring to provide effective relief and avoid side effects. ( EVIDENCE: fair for short-term effectiveness, limited for long-term effectiveness) B) Up to 40 mg of morphine equivalent is considered as low dose, 41 to 90 mg of morphine equivalent as a moderate dose, and greater than 91 mg of morphine equivalence as high dose. ( EVIDENCE: fair) C) In reference to long-acting opioids, titration must be carried out with caution and overdose and misuse must be avoided. ( EVIDENCE: good) 8. A) Methadone is recommended for use in late stages after failure of other opioid therapy and only by clinicians with specific training in the risks and uses. ( EVIDENCE: limited) B) Monitoring recommendation for methadone prescription is that an electrocardiogram should be obtained prior to initiation, at 30 days and yearly thereafter. ( EVIDENCE: fair) 9. In order to reduce prescription drug abuse and doctor shopping, adherence monitoring by UDT and PMDPs provide evidence that is essential to the identification of those patients who are non-compliant or abusing prescription drugs or illicit drugs. ( EVIDENCE: fair) 10. Constipation must be closely monitored and a bowel regimen be initiated as soon as deemed necessary. ( EVIDENCE: good) 11. Chronic opioid therapy may be continued, with continuous adherence monitoring, in well-selected populations, in conjunction with or after failure of other modalities of treatments with improvement in physical and functional status and minimal adverse effects. ( EVIDENCE: fair). DISCLAIMER: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Effect of dronabinol on central neuropathic pain after spinal cord injury: a pilot study.

OBJECTIVE: To test the efficacy and safety of a cannabinoid, dronabinol, compared with an active control, diphenhydramine, in relieving neuropathic pain in persons with spinal cord injury. DESIGN: A randomized, controlled, double-blind, crossover pilot study. RESULTS: Seven adults with spinal cord injury and neuropathic pain below the level of injury participated. Two participants withdrew while receiving dronabinol, their first medication. For the remaining five participants, change in pain on a scale of 0-10 from baseline to the end of the maintenance phase did not differ significantly between the two medications (mean change, dronabinol: 0.20 ± 0.837, range = -1.00 to 1.00; diphenhydramine: -1.80 ± 2.490, range = -6.00 to 0; Wilcoxon Z = 1.63, P = 0.102). Similar results were found when the average of the two ratings during the maintenance phase was used (dronabinol: -0.20 ± 0.671, range = -0.50 to 1.00; diphenhydramine: -1.40 ± 1.245, range = -3.50 to -0.50; Wilcoxon Z = 1.60, P = 0.109). The most common side effects were dry mouth, constipation, fatigue, and drowsiness for both medications. CONCLUSIONS: On average, dronabinol was no more effective than diphenhydramine for relieving chronic neuropathic pain below the level of injury.

Management of painful vertebral hemangiomas with kyphoplasty: a report of two cases and a literature review.

BACKGROUND AND OBJECTIVES: Although uncommon, symptomatic vertebral hemangiomas can be a painful condition limiting daily activities. Balloon kyphoplasty is a developing technique that has successfully been used in the treatment of vertebral hemangiomas as reported in a few publications. The aim of this paper is to describe 2 cases of painful vertebral hemangiomas effectively treated with percutaneous balloon kyphoplasty and review the current literature. DESIGN AND METHODS: A 38-year-old male with a painful L5 biopsy-proven hemangioma and a 75-year-old female with a painful T12, hemangioma MRI-proven both presented with thoraco-lumbar pain. Physical exams correlated with imaging findings and no neurological symptoms were present. Both patients received conservative management including physical therapy and a variety of spinal injections without benefit. Percutaneous balloon kyphoplasty was subsequently performed on each patient to relieve pain. RESULTS: After kyphoplasty, both patients' pain resolved immediately and they were able to resume previous levels of activity. CONCLUSIONS: This case series demonstrates a successful response to vertebral augmentation using balloon kyphoplasty when other treatment modalities failed. When compared to traditional first line treatments such as vertebroplasty or lytic therapies, kyphoplasty may offer fewer procedural risks such as a decreased exposure to radiation, a decreased risk of excessive hemorrhage, and a decreased risk of cement leakage which may make it the preferred treatment of painful vertebral hemangiomas in the future.

Assessment of musculoskeletal examination skills: physiatry residents as evaluators and models.

OBJECTIVE: To evaluate the musculoskeletal examination (MSKE) skills of junior (postgraduate year [PGY] 2) physical medicine and rehabilitation (PM&R) residents and self-confidence with these skills, and to demonstrate changes in self-confidence in the MSKE skills of senior (PGY3 and PGY4) residents, who served as evaluators and models. DESIGN: Forty-one PGY2-4 residents participated in this retrospective cohort study, which was conducted within a residency program affiliated with two medical schools. Senior residents attended an instructional session in performing and evaluating MSKE skills, taught by a musculoskeletal physiatrist. The following week, junior residents were tested on their MSKE skills; nine seniors served as models, and another nine served as evaluators. Six seniors attended the instructional session only and did not participate in the evaluation. Juniors received a posttest teaching session on MSKE skills, before an unannounced repeat evaluation 5 mos later. All residents completed a survey regarding self-confidence in MSKE skills pre- and posttest teaching sessions. Performance of MSKE skills (based on PASSOR guidelines) and application of ACGME core competencies (medical knowledge, professionalism, interpersonal skills) were measured, and a survey was administered regarding self-confidence in MSKE skills. RESULTS: Posttest results showed a significant improvement of MSKE skills among juniors in the shoulder, lumbar spine, and knee examinations (P < 0.008), with the most robust improvement in the shoulder exam (P < 0.0001). Self-confidence of juniors in their MSKE skills increased significantly (P < 0.005). There was significant improvement (P < 0.008) in self-confidence in the MSKE skills of seniors who served as models and evaluators, but not in those who only attended the instructional session (P = 0.06). CONCLUSIONS: This evaluation and instructional method resulted in a significant improvement of MSKE skills of junior residents on formal testing. Using senior residents as evaluators and models improved their confidence in their own MSKE skills.