Methylene blue for intractable pain from oral mucositis related to cancer treatment: a randomized phase 2 clinical trial.

BACKGROUND: Oral mucositis (OM) in patients receiving cancer therapy is thus far not well managed with standard approaches. We aimed to assess the safety and effectiveness of methylene blue (MB) oral rinse for OM pain in patients receiving cancer therapy. METHODS: In this randomized, single-blind phase 2 clinical trial, patients were randomized to one of four arms: MB 0.025%+conventional therapy (CTx) (n = 15), MB 0.05%+CTx (n = 14), MB 0.1%+CTx (n = 15), or CTx alone (n = 16). Intervention groups received MB oral rinse every 6 h for 2 days with outcomes measured at days 1-2; safety was evaluated up to 30 days. The primary outcome measured change in the pain numeric rating scale (0-10) from baseline to day 2. Secondary outcome measured change in oral function burden scores from baseline to day 2, World Health Organization OM grades, morphine equivalent daily doses, and adverse events. The trial was registered with ClinicalTrials.gov ID: NCT03469284. RESULTS: Sixty patients (mean age 43, range 22-62 years) completed the study. Compared with those who received CTx alone, those who received MB had a significant reduction of pain scores at day 2 of treatment (mean ± SD); 0.025%: 5.2 ± 2.9, 0.05%: 4.5 ± 2.9, 0.1%: 5.15 ± 2.6) and reduction of oral function burden scores (0.025%: 2.5 ± 1.55, 0.05%: 2.8 ± 1.7, 0.1%: 2.9 ± 1.60). No serious adverse events were noted, but eight patients reported burning sensation of the oral cavity with the first dose, and this caused one patient to discontinue therapy. CONCLUSIONS: MB oral rinse showed significant pain reduction and improved oral functioning with minimal adverse effects. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT03469284.

Methylene Blue for the Treatment of Intractable Pain Associated with Oral Mucositis.

Oral mucositis is a common and often debilitating complication among cancer patients receiving radiation therapy to the head and neck or chemotherapy agents, or undergoing hematopoietic stem cell transplantation. Pain and decreased oral function associated with oral mucositis may persist long after the conclusion of therapy. Although most patients respond to conservative management, a subset of patients develops intractable pain with severe consequences. For some, the use of total parenteral nutrition with insertion of percutaneous endoscopic gastrostomy feeding tubes is the only alternative. Current recommendations to treat mucositis and its related pain include basic oral care, bland oral rinses, topical anesthetics, and systemic analgesics. We believe that chemical neurolysis of the affected areas with methylene blue used as an oral rinse is a noninvasive, efficient, safe, and cost-effective alternative that can provide prolonged analgesia in patients with intractable pain of oral mucositis. The benefits of this therapy are reflected in its improvement of patients' quality of life by enabling oral feeding and controlling pain. We report a series of 5 consecutive patients with intractable oral mucositis-related pain despite conventional treatment with systemic opiates. All 5 patients responded well to the use of 0.05% methylene blue as mouth rinse, demonstrating sustained analgesia over 3 weeks. The treatment was tolerated well, and overall patient satisfaction was very high. We also observed that methylene blue rinse significantly reduced the total opioid requirement, as demonstrated by reductions in the patients' morphine equivalent daily dose scores after its use. Our case series suggests that 0.5% methylene blue oral rinse therapy is an effective and inexpensive modality that can be used safely to palliate intractable oral pain in patients with mucositis associated with cancer treatment. To our knowledge, this is the first report using this therapy to treat pain from oral mucositis.

Genicular nerve neurolysis with phenol for chronic knee pain: A case series.

Chronic knee pain continues to be a common complaint amongst patients and continues to grow as the elderly population lives longer. New ways to treat chronic pain conditions, including chronic knee pain, are necessary as increased co-morbidities prevent patients from being surgical candidates. Recently, the genicular nerves have received more attention due to their role in innervating the anterior knee joint capsule as well as the intraarticular and extraarticular knee ligaments. Initial interest in the genicular nerve included radiofrequency ablation. RFA while effective, also brings with it increased procedure and equipment costs with a non-response rate of around 25%. Alcohol neurolysis of the genicular nerve is being seen as a potential alternative, low-cost, effective option for relieving chronic knee pain in patients. Previous case reports have focused on the use of alcohol, we report the use of phenol for genicular neurolysis. Of the four genicular nerve branches, only three are targeted due to the proximity of the inferolateral genicular nerve to the common peroneal nerve. The purpose of this case report is to show the effectiveness of phenol for neurolysis of the genicular nerves in relieving chronic knee pain in patients in which surgery is not an option.

Ultrasound-guided superficial cervical plexus block for cancer-related clavicle pain.

Pain is one of the most feared conditions a cancer patient may face. Bone is a common site of metastasis in many malignancies, including breast, prostate, kidney, and lung cancer. Conventional therapy for tumor-related bone pain involves the use of opioids, non-steroidal anti-inflammatory drugs, and bisphosphonates. Palliative radiation therapy may be incorporated for refractory bone pain. We describe an innovative case of cancer-related clavicle pain successfully managed with a superficial cervical plexus block in an opioid-intolerant patient. Considering the lack of guidelines for pain interventions in this setting, such peripheral nerve blocks may be a useful adjunctive tool in refractory cancer pain management.

It's Not All in Your Head: Thoracic Manifestations of Neurologic Diseases and Disorders.

Myriad conditions may affect both the neurologic system and the thorax, while other diseases primarily affecting the thorax may manifest with neurologic abnormalities. Correlation of signs, symptoms, and imaging findings in the neurological system with those in the thorax can help diagnose certain conditions and/or guide further diagnostic work-up and treatment. We will review and illustrate the imaging appearance of several systemic/neurological diseases with thoracic manifestations as well as discuss conditions in the thorax that can lead to neurologic symptoms.

Sacroiliac joint pain following iliac-bone marrow aspiration and biopsy: a cohort study.

Background: Sacroiliac joint (SIJ) pain is a common source of lower back pain; the factors associated have not been studied in cancer patients. Observing patients with bone marrow aspiration and biopsy (BMAB) who subsequently developed SIJ-pain led to this investigation. Aim: To investigate this possible relationship. Methods: A cohort study of cancer patients diagnosed with SIJ pain. The association of BMAB with SIJ pain was evaluated, as were variables that differed between the groups. Results: The prevalence of SIJ pain was 4.95% (231/4669). Among 231 patients with SIJ pain, 34% (78/231) did not have prior history of lower back pain and had undergone BMAB prior to their diagnosis of SIJ pain. A statistically significant association between BMAB-SIJ-pain was found (p < 0.01). Conclusion: We found linear correlation between BMAB and subsequent SIJ pain.

Oral pain associated with cancer therapy, a pain medicine perspective.

Cancer therapy-induced oral mucositis (CTIOM) can cause intolerable oral pain resulting in difficulty in chewing, swallowing and speaking. Thus, leading to patients requiring aggressive measures, such as parenteral feeding, the placement of gastric feeding tubes and discontinuation of oncologic treatments. Although, pain is the debilitating symptom, current efforts seem to focus independently in the histological damage, not in pain and symptom care. Current strategies for managing pain from CTIOM entail maintaining oral hygiene and the use of oral rinses, topical anesthetics, prophylactic antimicrobials and systemic analgesics such as opioids. Novel therapies, such as methylene blue oral rinse, are being investigated, with positive outcomes. Therefore, there is a need to identify treatment modalities for pain of CTIOM. Ideally, this should be noninvasive, safe and cost-effective, while providing sustained analgesia.

Unilateral Lower Extremity Pain Due to Malignancy Managed With Cordotomy: A Case Report.

Cancer pain management is comprehensive, and it generally begins with pharmacotherapy in a step-wise approach per analgesic guidelines established decades ago by the World Health Organization. This analgesic ladder involves the prescribing of co-analgesics, adjuvants, and opioids, with each step depending on pain severity. Although the majority of cancer pain responds to this strategy, there exist patients who do not respond adequately or experience significant side effects or intolerance to pain medications. It is in these patients whom clinicians consider interventional approaches. One approach to manage unremitting unilateral malignant pain includes evaluation for cordotomy, which is an approach that has been effective in such cases. We present a patient with breast cancer metastatic to the pelvis, with associated severe pelvic and right lower limb pain. Due to progressive disease, her pain worsened despite aggressive opioid dose escalations. She ultimately underwent percutaneous left anterolateral cervical cordotomy for malignant right leg pain, resulting in complete resolution of leg pain. We propose that, in select patients with neoplasm-related pain, cordotomy may prove very effective. LEVEL OF EVIDENCE: V.

Cancer pain assessment.

PURPOSE OF REVIEW: Adequate cancer pain assessment using valid and reliable tools is essential for proper cancer pain management. Because cancer pain can be a complex construct, assessment of its many domains should be conducted using multidimensional tools. Furthermore, there is a need to develop a standard, consensus classification system for prognosis of cancer pain. RECENT FINDINGS: Unidimensional tools for assessing cancer pain are useful for measuring cancer pain intensity. Other domains and symptoms of the cancer pain experience are assessed using a variety of multidimensional tools. There is a lack of agreement on a standard assessment tool or a standard classification system for cancer pain, although research continues to be undertaken to develop such resources for clinical and research purposes. SUMMARY: Many pain and symptom assessment tools exist for use in the cancer patient, including the Brief Pain Inventory, the McGill Pain Questionnaire, the MD Anderson Symptom Inventory, and the Edmonton Symptom Assessment System, among others. Recent literature reveals the move toward translating these and other tools to electronic applications. Further study is also underway to create a standard, prognostic classification system for cancer pain.

Recent advances in select interventional approaches to cancer-related pain.

SUMMARY Interventional approaches for cancer-related pain have demonstrated utility and safety as a component of multimodal pain management. A number of techniques have been developed and implemented to manage the variety of cancer pain conditions and syndromes that exist as a result of the underlying malignant process and its associated oncologic treatment. These procedural pain modalities continue to evolve with advances in experience, understanding and technology in the field. Neurostimulation, vertebral augmentation with stabilization and intrathecal drug delivery, are prime examples of innovative approaches in interventional pain medicine for cancer pain with continued improvement in design to better achieve adequate analgesia and reduce risk. The intent of this article is to describe the aforementioned interventions and recent developments pertaining to them.

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.