Cannabinoids as a Potential Alternative to Opioids in the Management of Various Pain Subtypes: Benefits, Limitations, and Risks.

INTRODUCTION: Pain is a global phenomenon encompassing many subtypes that include neuropathic, musculoskeletal, acute postoperative, cancer, and geriatric pain. Traditionally, opioids have been a mainstay pharmacological agent for managing many types of pain. However, opioids have been a subject of controversy with increased addiction, fatality rates, and cost burden on the US healthcare system. Cannabinoids have emerged as a potentially favorable alternative or adjunctive treatment for various types of acute and chronic pain. This narrative review seeks to describe the efficacy, risks, and benefits of cannabinoids as an adjunct or even potential replacement for opioids in the treatment of various subtypes of pain. METHODS: In June of 2022, we performed a comprehensive search across multiple databases for English-language studies related to the use of cannabinoids in the treatment of various types pain: neuropathic pain, musculoskeletal pain, acute postoperative pain, cancer pain, and geriatric pain. Data from meta-analyses, systematic reviews, and randomized control trials (RCTs) were prioritized for reporting. We sought to focus our reported analysis on more recent literature as well as include older relevant studies with particularly notable findings. RESULTS: There is conflicting evidence for the use of cannabinoids in the management of pain. While cannabinoids have shown efficacy in treating specific chronic pain subtypes such as neuropathic pain, fibromyalgia pain, and geriatric pain, they do not show as clear benefit in acute postoperative and the majority of musculoskeletal pain syndromes. Data trends towards cannabinoids having a positive effect in treating cancer pain, but results are not as conclusive. To date, there is a paucity of data comparing cannabinoids directly to opioids for pain relief. Overall, the side effects of cannabinoids appear to be relatively mild. However, there is still potential for addiction, altered brain development, psychiatric comorbidities, and drug-drug interactions. CONCLUSION: Cannabinoids may be effective in specific subtypes of pain, but current evidence and guidelines do not yet support its use as the first-line treatment for any type of acute or chronic pain. Rather, it may be considered a good adjunct or alternative for patients who have failed more typical or conservative measures. Additional studies are needed with standardized forms of cannabinoids, route of delivery, and dosing for greater-powered analysis. Providers must weigh the individualized patient risks, benefits, and concurrent medication list in order to determine whether cannabinoids are appropriate for a patient's pain treatment plan.

Radiofrequency Ablation for Craniofacial Pain Syndromes.

Headache disorders and trigeminal neuralgia are common conditions representing the types of craniofacial pain syndrome that can significantly impact quality of life. Many cases are refractory to traditional pharmacologic treatments, whether oral or intravenous. Radiofrequency ablation has been increasingly used as a tool to treat resistant, chronic pain of both of these disorders. Multiple studies have been reported that illustrate the efficacy of radiofrequency ablation in the treatment of the numerous headache subtypes and trigeminal neuralgia.

Preliminary effects of low-intensity focused ultrasound treatment program for cancer-related neuropathic pain.

Aim: To evaluate the effectiveness of low-intensity focused ultrasound (LIFU) therapy in the management of cancer-related neuropathic pain (CNP). Methods: A retrospective review with 22 patients with CNP treated with LIFU therapy (frequency 3 Hz, 3 W/cm2, pulse mode duty cycle 50%) was conducted. Results: Out of the 22 patients, 15 had CNP secondary to chemotherapy-induced peripheral neuropathy. Compared with baseline, there was a significant reduction in numeric pain rating scale (p < 0.001). Additionally, 76.5% of patients (n = 13) were considered to be responders to LIFU therapy. Conclusion: LIFU therapy may be a viable treatment modality in the management of CNP, specifically chemotherapy-induced peripheral neuropathy, with a minimal side effect profile. Larger, prospective studies with a structured protocol are necessary.

Lay abstract With recent advancements in oncological treatments, there has been an increase in the number of cancer survivors. This has led to an increase in prevalence and burden of long-term side effects of oncological disease and associated treatments. Cancer-related neuropathic pain (CNP) is a debilitating pain condition that develops in the setting of direct tumor burden or as a result of cancer-related treatments, such as chemotherapy. Management can be challenging and clinicians are often limited to pharmacological agents and more invasive modalities. This study evaluated the effectiveness of low-intensity focused ultrasound (LIFU), a noninvasive, externally applied therapeutic ultrasound device, as a treatment for CNP. Twenty-two patients with CNP were treated with LIFU and found to have significant reduction in pain, suggesting LIFU may be an effective treatment modality in the management of CNP. This pilot study has laid the ground work for future prospective studies to further investigate the effects of LIFU on CNP.

Interventional Therapies for Pain in Cancer Patients: a Narrative Review.

PURPOSE OF REVIEW: Pain is a prevalent symptom in the lives of patients with cancer. In light of the ongoing opioid epidemic and increasing awareness of the potential for opioid abuse and addiction, clinicians are progressively turning to interventional therapies. This article reviews the interventional techniques available to mitigate the debilitating effects that untreated or poorly treated pain have in this population. RECENT FINDINGS: A range of interventional therapies and technical approaches are available for the treatment of cancer-related pain. Many of the techniques described may offer effective analgesia with less systemic toxicity and dependency than first- and second-line oral and parenteral agents. Neuromodulatory techniques including dorsal root ganglion stimulation and peripheral nerve stimulation are increasingly finding roles in the management of oncologic pain. The goal of this pragmatic narrative review is to discuss interventional approaches to cancer-related pain and the potential of such therapies to improve the quality of life of cancer patients.

Hippocampal magnetization transfer ratio at 3T: validation of automated postprocessing and comparison of quantification metrics.

BACKGROUND: To investigate the reliability of a novel magnetization transfer ratio (MTR) postprocessing technique for the hippocampus using histogram analysis, and compare results to more established volumetric measurements. This study is conducted in healthy volunteers as a precursor to future applications regarding progressive neurologic diseases, such as Alzheimer's disease. METHODS: Eight healthy subjects were scanned twice with interval of 1 week using quantitative magnetic resonance imaging (MRI). Automated pixel-wise analysis was performed for the hippocampal regions of each patient. Reliability was assessed using intraclass correlation coefficients (ICCs), coefficients of variation (COVs), and instrumental standard deviation (ISD). RESULTS: Reliable metrics were 25th percentile, median, 75th percentile, peak location, and mean approach (ranges: ICC = .93-.96, COV = 2.71-3.88%, ISD .78-1.01). Histogram peak height had ICC below .7, and a COV above 10%. Volumetric measurements had (ICC = .95-.97, COV = 1.43-3.39%). CONCLUSION: Excellent scan-rescan reproducibility (ICC > .9, COV < 10%) was observed for specific MTR histogram metrics and the mean MTR approach. These results are comparable to the volumetric approach. Future studies can examine the possibility that MTR changes precede morphological changes as this study suggests that both MTR and volumetric measurements of the hippocampus can be used as reliable imaging tools.

Comprehensive brain analysis with automated high-resolution magnetization transfer measurements.

PURPOSE: To enhance the reliability and spatial resolution of magnetization transfer ratio (MTR) measurements for interrogation of subcortical brain regions with an automated volume of interest (VOI) approach. MATERIALS AND METHODS: A 3D magnetization transfer (MT) sequence was acquired using a scan-rescan imaging protocol in nine healthy volunteers. VOI definition masks for the MTR measurements were generated using FreeSurfer and compared to a manual region of interest (ROI) approach. (The longitudinal stability of MTR was monitored using agar gel phantom over a 5-month period.) Intraclass correlation coefficients (ICCs), coefficients of variation (CVs), and instrumental standard deviation (ISD) were determined. RESULTS: CVs ranged from 1.29%-2.64% (automated) vs. 1.30%-3.40% (manual). ISDs ranged from 0.62-1.10 pu (automated) vs. 0.68-1.67 pu (manual). The SD of the running difference was 1.70% for the phantom scans. The Bland-Altman method indicated interchangeability of the automated VOI and manual ROI measurements. CONCLUSION: The automated VOI approach for MTR measurement yielded higher ICCs, lower CVs, and lower ISDs compared to the manual method, supporting the utility of this strategy. These results demonstrate the feasibility of obtaining reliable MTR measurements in hippocampus and other critical subcortical regions.

Sub-millimeter isotropic MRI for segmentation of subcortical brain regions and brain visualization.

PURPOSE: To evaluate a rapid sub-millimeter isotropic spoiled gradient-echo (nonselective SPGR) to facilitate the brain subcortical segmentation and the visualization of brain volume compared with the commonly accepted inversion recovery-prepared SPGR (SPGR-IR) technique. MATERIALS AND METHODS: The feasibility of the nonselective SPGR was evaluated for two segmentation algorithms. FAST was used to segment the brain into constituent tissue classes (white matter, gray matter, cerebrospinal fluid) and FreeSurfer was used to segment specific subcortical structures (hippocampus, caudate, putamen, and thalamus). Localized apparent signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) values for nonselective SPGR and the SPGR-IR were compared for the studied subcortical regions. The three-dimensional volume rendering was generated to evaluate the nonselective SPGR and the SPGR-IR for brain visualization. RESULTS: In basal ganglia regions, nonselective SPGR allows for consistent segmentation results for both FAST and FreeSurfer. This sequence also better differentiated gray/white matter compared with SPGR-IR. An approximate two-fold improvement of image quality in apparent SNR and CNR was indicated for subcortical brain anatomical structures with nonselective SPGR versus SPGR-IR. The nonselective SPGR improved clarity and yielded a more realistic depiction of the brain surface for visualization compared with SPGR-IR. CONCLUSION: Compared with SPGR-IR, nonselective SPGR allows for consistent segmentation results for basal ganglia regions and improved clarity for visualization of the brain.

Statistical evaluations of the reproducibility and reliability of 3-tesla high resolution magnetization transfer brain images: a pilot study on healthy subjects.

Magnetization transfer imaging (MT) may have considerable promise for early detection and monitoring of subtle brain changes before they are apparent on conventional magnetic resonance images. At 3 Tesla (T), MT affords higher resolution and increased tissue contrast associated with macromolecules. The reliability and reproducibility of a new high-resolution MT strategy were assessed in brain images acquired from 9 healthy subjects. Repeated measures were taken for 12 brain regions of interest (ROIs): genu, splenium, and the left and right hemispheres of the hippocampus, caudate, putamen, thalamus, and cerebral white matter. Spearman's correlation coefficient, coefficient of variation, and intraclass correlation coefficient (ICC) were computed. Multivariate mixed-effects regression models were used to fit the mean ROI values and to test the significance of the effects due to region, subject, observer, time, and manual repetition. A sensitivity analysis of various model specifications and the corresponding ICCs was conducted. Our statistical methods may be generalized to many similar evaluative studies of the reliability and reproducibility of various imaging modalities.