Haloperidol for Pain Management: A Narrative Review.

The use of haloperidol in pain management has been a topic of interest for several decades. Haloperidol is a widely used antipsychotic medication with unique pharmacologic properties that make it a potential candidate for pain management. However, the efficacy and safety of haloperidol for pain management remain controversial. This narrative review provides a summary of the current literature on the use of haloperidol for pain management, including its pharmacology, clinical effectiveness, adverse effects, and dosing regimens. We performed a comprehensive search of the literature for this review. The most robust clinical data from the past decade suggest that haloperidol has good efficacy in the treatment of pain related to gastroparesis and migraines and has shown promise for opioid use reduction in patients with chronic pain or receiving palliative care. The overall side effect profile is excellent, with zero reported events of QT-related cardiac arrest and minimal reports of sedation and transient extrapyramidal effects such as akathisia. Dosing regimens used were heterogeneous, with most ranging from 1 to 5 mg per dose via intravenous, intramuscular, or oral route. Studies with designs that isolated the effects of haloperidol from combinations of other drugs were extremely limited. Further high-quality prospective studies are needed to determine the ideal role of haloperidol in the routine clinical management of painful conditions.

Methylene Blue, a Unique Topical Analgesic: A Case Report.

Background: Rectal prolapse is a circumferential, full-thickness protrusion of the rectum through the anus, which, if not properly managed, may become incarcerated and pose a risk of strangulation. This pathology is rarely a medical emergency unless a complication is encountered. Such complications include infection, necrosis, perforation, incarceration, and uncontrolled pain. Case Presentation: We report a case of an elderly patient with pain associated with chronic rectal prolapse. Surgical intervention had been ruled out, and there had been no pain relief after using systemic analgesics. Case Management: Based on increasing reports of analgesic properties, topical methylene blue (MB) 0.1% was applied externally at the prolapsed organ, obtaining pain relief. Case Outcome: The patient experienced immediate and long-lasting pain relief; MB applications were continued every 12 hours as needed. After this therapy, the patient was no longer in need of systemic analgesics. No side effects were reported. Conclusion: Topical MB may be an effective analgesic for the management of pain associated with chronic rectal prolapse. This treatment might be extrapolated to other clinical scenarios of tegumentary pain. Similar use has been shown to be safe and effective in other pathologies, including pain in oral mucositis associated with cancer therapy.

Diagnostic and therapeutic value of intracellular biomarker testing in chronic pain.

Aim: Micronutrient and metabolic compound supplementation as a method of treating chronic pain is not well understood. Case: A 58 year-old woman presented with refractory painful neuropathy. She did not respond to conservative treatment and was seeking spinal cord stimulator implantation. She underwent a biomarker panel that revealed low intracellular levels of multiple compounds. As she supplemented her deficiencies, her symptoms fully resolved, and the implant was no longer indicated. Discussion: Micronutrient and metabolic compound testing could potentially expand non-invasive treatment options for patients with refractory chronic pain. Caution should be exercised given limited regulatory oversight in the supplement industry and actively ongoing nutritional research. Conclusion: Biomarker testing panels may be a useful adjunct in the management of refractory neuropathic pain.

Methylene Blue for the Treatment of Radiation-Induced Oral Mucositis during Head and Neck Cancer Treatment: An Uncontrolled Cohort.

Pain from radiation-therapy-induced oral mucositis during head-neck cancer treatment is aggravated by concurrent chemotherapy and commonly fails traditional treatments. To explore safe and sustainable alternatives, we investigated methylene blue oral rinse to reduce radiation-therapy-related oral mucositis pain. For this, we conducted a retrospective observational cohort study in a tertiary-care academic care cancer center including 85 patients with refractory oral mucositis pain during radiation therapy for head-neck cancer. Changes in pain (scale 0-10), oral function burden (scale 0-6) and requirement for percutaneous endoscopic gastrostomy tube placement were measured. Among 58 patients, 60% received radiation therapy alone and 40% received concurrent chemotherapy-radiation therapy. Methylene blue oral rinse (MBOR) significantly decreased oral mucositis pain for at least 6.2 h (median + SD 8 ± 1.68 before vs. 2 ± 2.20 after; p < 0.0001) and oral function burden (3.5 ± 1.33 before vs. 0 ± 0.86 after; p < 0.0001). Eleven patients (19%) had percutaneous endoscopic gastrostomy tubes placed before using methylene blue oral rinse; subsequently, four (36%) resumed oral alimentation after methylene blue oral rinse. Two patients (3%) required percutaneous endoscopic gastrostomy tubes despite methylene blue oral rinse. Minimal adverse events were reported (n = 9, 15%). Our study showed that methylene blue oral rinse was an effective and safe topical treatment for opioid-refractory oral pain from oral mucositis associated with radiation therapy for head-neck cancer.

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.

Temporal characterization of acute pain and toxicity kinetics during radiation therapy for head and neck cancer. A retrospective study.

Objectives: Pain during Radiation Therapy (RT) for oral cavity/oropharyngeal cancer (OC/OPC) is a clinical challenge due to its multifactorial etiology and variable management. The objective of this study was to define complex pain profiles through temporal characterization of pain descriptors, physiologic state, and RT-induced toxicities for pain trajectories understanding. Materials and methods: Using an electronic health record registry, 351 OC/OPC patients treated with RT from 2013 to 2021 were included. Weekly numeric scale pain scores, pain descriptors, vital signs, physician-reported toxicities, and analgesics were analyzed using linear mixed effect models and Spearman's correlation. Area under the pain curve (AUCpain) was calculated to measure pain burden over time. Results: Median pain scores increased from 0 during the weekly visit (WSV)-1 to 5 during WSV-7. By WSV-7, 60% and 74% of patients reported mouth and throat pain, respectively, with a median pain score of 5. Soreness and burning pain peaked during WSV-6/7 (51%). Median AUCpain was 16% (IQR (9.3-23)), and AUCpain significantly varied based on gender, tumor site, surgery, drug use history, and pre-RT pain. A temporal increase in mucositis and dermatitis, declining mean bodyweight (-7.1%; P < 0.001) and mean arterial pressure (MAP) 6.8 mmHg; P < 0.001 were detected. Pulse rate was positively associated while weight and MAP were negatively associated with pain over time (P < 0.001). Conclusion: This study provides insight on in-depth characterization and associations between dynamic pain, physiologic, and toxicity kinetics. Our findings support further needs of optimized pain control through temporal data-driven clinical decision support systems for acute pain management.

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.

Non-Invasive Pelvic Floor Rehabilitation in Cancer Population: An Incomplete Cohort.

BACKGROUND: Pelvic floor dysfunction and its associated symptoms are a common clinical challenge in the cancer population. Despite the noninvasive nature of pelvic floor rehabilitation (PFR) for this condition and the promising clinical results observed with its use, PFR appears to be an underused therapy. OBJECTIVES: The purpose of this study was to quantify the association between physical therapy of the pelvic floor and its effect on pain relief and the associated symptoms in cancer patients with pelvic floor dysfunction. STUDY DESIGN: Retrospective cohort study. METHODS: With the use of an electronic database in our pain medicine department, we retrospectively quantified the pain relief and symptom improvement in patients diagnosed as having chronic pelvic floor dysfunction who had undergone PFR. RESULTS: Of the 68 patients available for analysis, 49 met the inclusion criteria. Baseline characteristics of included patients were generally similar. The duration of pelvic pain before PFR was 53.7 months (mean) (SD, 182.5 months; median, 12 months). Of the 49 study patients, 23 (47%) had bladder dysfunction, 24 (49%) had dyspareunia, 2 (4%) had erectile dysfunction, and one (2%) had rectal dysfunction. Most symptoms associated with pelvic floor dysfunction resolved after PFR. LIMITATIONS: Single-center, small data, retrospective study. CONCLUSIONS: PFR is an effective tool for treating the pain associated with pelvic floor dysfunction and its related symptoms. This conservative approach can contribute to lowering the use of opiate analgesics.

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.

Methylene Blue for the Treatment of Intractable Pain From Oral Mucositis Related to Cancer Treatment: An Uncontrolled Cohort.

BACKGROUND: Oral mucositis is a complication of cancer therapy, causing severe pain that affects oral functioning, nutrition, and quality of life, as well as therapy nonadherence or dose-limiting toxicity. Anecdotal experience has suggested that methylene blue (MB) oral rinse may be an effective and safe treatment of this oral pain. METHODS: To evaluate the efficacy and safety of MB oral rinse for the treatment of oral pain due to mucositis in patients with cancer, we retrospectively evaluated patients who experienced refractory pain despite conventional therapy. RESULTS: We identified 281 patients who received MB oral rinse. Most were receiving treatment for leukemia (n=85; 30.3%) and head and neck squamous cell carcinoma (n=84; 29.9%). The most common treatments were radiation therapy alone (n=108; 38.4%) and chemoradiation (n=86; 30.6%). Median duration of symptoms was 14 days. Mean (SD) numeric rating scale pain scores were 7.7 (1.83; median, 8) before MB oral rinse and 2.51 (2.76; median, 2) after MB oral rinse (P<.0001). Most patients achieved pain control within the first 3 doses. The effectiveness of MB oral rinse was independent of patient age, sex, cancer type, cancer stage, MB dilution, and pain duration or baseline pain scores. The lowest response to treatment was reported in individuals with esophageal mucositis. Few patients experienced adverse effects of MB oral rinse (n=13; 4.6%); 10 had a transient burning sensation, 2 had transient blue discoloration of the teeth and mouth, and 1 had increased pain. CONCLUSIONS: MB oral rinse is an effective and safe treatment for refractory pain from oral mucositis related to cancer treatment.

Lack of association between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and pain improvement in patients with oral cancer.

BACKGROUND: There is a growing body of literature implicating angiotensin II in the modulation of tumour-associated inflammation and pain. However, the impact of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) on pain and inflammation has not yet been studied in oral cancers. The objective is to investigate the role of ACEi and ARB pharmacotherapy on preoperative pain and inflammatory biomarkers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), in patients with oral cancer. METHODS: We performed a retrospective study on patients who underwent oral cancer surgery. The Wilcoxon rank-sum test or Kruskal-Wallis analysis was used to evaluate differences in demographic, tumour-related and preoperative characteristics and amongst patients using ARBs, ACEis and no treatment. Multivariable analysis was fitted to estimate the effects of important covariates on severe preoperative pain. RESULTS: A total of 162 patients with oral malignancies were included in the study. After adjusting for significant covariates, patients with perineural invasion were found to have higher levels of pain (p = 0.0278). Similarly, patients taking ARBs were found to have lower levels of perineural invasion (p = 0.035). The analysis did not demonstrate a significant difference in pain levels when comparing ARBs or ACEis to the no treatment group (p = 0.250). Furthermore, the use of ARB or ACEi did not significantly alter preoperative NLR (p = 0.701) or MLR (p = 0.869). CONCLUSIONS: When compared to no treatment, ARBs and ACEis are not associated with significant analgesic effect or decreased inflammatory scores (NLR, PLR and MLR).

High-flow oxygen and pro-serotonin agents for non-interventional treatment of post-dural-puncture headache.

OBJECTIVE: Post dural puncture headache (PDPH) is a common complication in patients following diagnostic or therapeutic lumbar puncture, procedures requiring epidural access, and spinal surgery. Epidural blood patch (EBP), the gold standard for the treatment of this pathology requires training not provided to emergency physicians. In addition, the presence of concomitant pathology and abnormal laboratory values are contraindications to perform EBP. In presence of these limitations, we sought for a non-interventional management of PDPH utilizing high-flow oxygen and pro-serotonin agents. We reviewed the mechanism of action of this therapy METHODS: To illustrate our proposal, we report a series of twelve consecutive patients with PDPH treated with high-flow oxygen therapy at 12 L/min via a non-rebreathing mask and intravenous metoclopramide. RESULTS: All patients were treated with this conservative therapy, no adverse reactions were observed. After the intervention, the headache resolved without further indications for PDPH. CONCLUSION: Our series suggests that combining high-flow oxygen and pro-serotonin agents such metoclopramide in the ED might be a feasible option as effective as the invasive methods used in treating PDPH. This therapy appears to be efficient and to minimize risk, cost and side effects. It presents an easily accessible alternative that should be considered when PDPH is not a viable option.

Sacroiliitis in cancer patients: a review of current literature.

The sacroiliac (SI) joint can be directly jeopardized by malignancy and indirectly by ergonomic changes of pelvic obliquity that introduces uneven weight distribution. Cancer treatment can exacerbate preexisting arthritis and cause diffuse arthropathies, but these are unlikely to be isolated to the SI joint. The cancer population is exposed to unique stressors that might facilitate development of SI joint pain that includes cancer itself and therapy-related complications. Like the general population, cancer patients are subject to aging and BMI and musculoskeletal structural changes that affect symmetric body functioning and posturing. No frank association between sacroiliitis and cancer has been identified. Therefore, we believe there is a need to characterize any relationship between cancer and SI joint dysfunction and pain.

Normal Saline Trigger Point Injections vs Conventional Active Drug Mix for Myofascial Pain Syndromes.

BACKGROUND: Myofascial pain syndrome (MPS) originates in the muscle and fascia. MPS presents with referred pain specific for each muscle and a trigger point that reproduces the symptoms. Trigger-point-injection (TPI) is an effective approach to treating MPS. Some TPI agents, however, are associated with systemic and local side effects. OBJECTIVE: The aim of this study was to evaluate the effectiveness of TPI with a conventional active drug mixture (CADM) vs. that with normal saline solution (NS) alone in patients with MPS presenting to the emergency department (ED). METHODS: Adults with MPS diagnosed in the ED, participants were randomly assigned to receive TPI with NS or with CADM. Pain intensity was scored using a 0-10 numeric rating scale prior to and after TPI, before discharge and 2 weeks after TPI. RESULTS: Among 48 patients analyzed, 23 received TPI with NS. The mean pain scores were as follows: immediately before TPI, 7.59 (NS) and 7.44 (CADM); immediately after TPI, 2.22 (NS) and 1.76 (CADM); prior to discharge, 1.52 (NS) and 1.76 (CADM). At 2-week follow up, the mean pain scores were 4.29 (NS) and 4.14 (CADM). Pain was significantly reduced after TPI in both groups. At 2 weeks, the mean pain scores were similar between the groups. No adverse events were reported. CONCLUSION: In cases of MPS in the ED, pain can be controlled with TPI independent of the injectate. TPI with NS may be preferred over CADM because of its lower cost and more favorable side effect profile.

Recurrence of complex regional pain syndrome after administration of adenosine.

Background: The effects of adenosine in acute chronic pain are not clear. Literature supports both a pronociceptive/inflammatory role of the A2aR/A2bR and antihyperalgesia/allodynia with A1Rs/A3Rs. Adenosine could participate in the reactivation of chronic regional pain syndrome (CRPS) through inflammatory pathways and via A2Rs. Plastic changes in the brain CRPS-related overlap with those seen in systemic inflammation and persist even after symptoms of CRPS resolve. Aim: To illustrate the hypothesis that intravenous adenosine can reactivate dormant CRPS. Case report: An individual with successfully treated CRPS developed supraventricular tachycardia, he was treated with intravenous adenosine. Shortly after a second dose, he developed severe pain at a lower limb from relapsed CRPS. Treatment included lumbar sympathetic block, physical therapy and pharmacological agents. Conclusion: Intravenous adenosine can reactivate dormant CRPS. Its potential pronociceptive role in CRPS calls for further studies to better elucidate the underlying mechanisms.

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.

Subclinical Peripheral Neuropathy in Patients with Head and Neck Cancer: A Quantitative Sensory Testing (QST) Study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and chronic complication associated with cancer treatment. Prior investigations have demonstrated the presence of subclinical peripheral neuropathy in patients with colorectal cancer even before the patients had received chemotherapy. OBJECTIVE: To investigate subclinical peripheral neuropathy of the upper limbs in patients with squamous cell carcinoma (SCC) of the head and neck which developed before their exposure to neurotoxic anticancer agents. STUDY DESIGN: Retrospective analysis. METHODS: With the use of our quantitative sensory testing (QST) data bank, we retrospectively assessed the afferent fiber function of 25 patients with SCC of the head and neck before they had received chemotherapy (the patient group) and compared our findings with those from 23 healthy control patients. Skin temperature, sensorimotor function, sharpness detection, thermal detection, and touch detection (using both von Frey monofilaments and the Bumps detection test) were measured. RESULTS: Touch thresholds were statistically higher in the patient group than in the healthy volunteer group at the palm (mean [± SD], 0.54 g [± 0.07 g] and 0.27 g [± 0.05 g], respectively [P < 0.01]) and at the forearm (0.74 g [± 0.12 g] and 0.41 g [± 0.08 g] [P < 0.05]). There was also a clear deficit in touch sensation as indicated by a Bumps detection threshold in patients of 6.5 µm ± 0.8 µm and in controls of 3.7 µm ± 0.5 µm. This yields an elevation in threshold to 165% in the patients relative to that of the control volunteers. The grooved pegboard test showed delayed completion times for patients compared with controls, with differences of 18.65 seconds in the dominant hand and of 23.36 seconds in the nondominant hand. The sharpness detection thresholds did not differ between patients and volunteers. LIMITATIONS: Inadequacies in the original data acquisition and documentation of the QST and the medical records could not be addressed due to the retrospective nature of the study. In addition, based on available information, we did not find an objective parameter able to correlate the QST findings with pre-pain levels. CONCLUSION: Patients with SCC were found to have deficits in sensory function before undergoing treatment, suggesting that cancer itself alters peripheral nerve function and may contribute to the development of CIPN. These results confirm the sensitivity of the Bumps detection test and highlight its potential role in early detection of peripheral neuropathy, especially in cancer patients for whom chemotherapies associated with CIPN have been prescribed. KEY WORDS: Peripheral neuropathy, head and neck cancer, quantitative sensory testing.

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.