This narrative review seeks to delve into the different on and off-label medications commonly used with intrathecal drug delivery systems (IDDS) and their clinical applications specifically in pain management settings. This review utilizes a variety of studies including reviews, retrospective chart analyses, and more to analyze the current effectiveness of various pharmacological agents on reducing chronic pain through IDDS. The initial results of intrathecal delivery of these medications have provided benefit in pain reduction and overall patient satisfaction; however, this review will seek to analyze the current data and understanding and suggest areas of strength and improvement within the field and our current understanding.

Introduction Headaches are among the most prevalent and disabling sources of pain, affecting nearly half of adults worldwide. Many patients experience debilitating headaches refractory to conservative treatments, including pharmacotherapy, steroid injections, or other interventional therapies. Radiofrequency ablation (RFA) is a minimally invasive technique that uses controlled thermal energy to create targeted tissue necrosis, disrupting the nociceptive signaling within targeted sensory nerves, and is a promising therapy for patients with chronic headaches refractory to conservative treatments. The objective of this study is to evaluate the clinical efficacy of thermal RFA for chronic headache management by examining changes in pain scores and the duration and degree of symptom relief. Methods This retrospective chart review of this study investigates patients who received thermal RFA of the occipital, supraorbital, supratrochlear, infraorbital, infratrochlear, and/or anterior ethmoid nerves between 2015 and 2025. Preoperative and postoperative pain scores were assessed using the Visual Analogue Scale (VAS). Additionally, the duration of relief and any adverse events associated with the procedures were recorded. Paired t-tests were performed between preoperative and postoperative VAS pain scores to determine statistical significance, with a p-value of ≤ 0.05 denoting significance. Results In total, 940 procedures were reviewed; 108 were excluded, and 832 procedures from 464 patients were included. The 464 patients comprised 369 female and 95 male patients, with a mean age of 44.83 ± 15.99 years and body mass index (BMI) of 29.65 ± 7.44 kg/m². Average preoperative and postoperative VAS scores were 5.34 ± 2.01 and 3.04 ± 2.33, respectively, representing a statistically significant reduction (p < 0.001). Quantitative or qualitative improvement was reported in 68.63% of procedures, and 13.10% noted complete remission for a total of 81.73% experiencing pain relief, whereas 18.27% saw no change. Among effective cases, the mean improvement was 60.20 ± 28.54%, lasting an average of 7.47 ± 9.78 months. A total of 12 adverse events were reported. Conclusions These findings suggest that thermal RFA of pericranial nerves can offer meaningful, lasting relief for patients with neuralgic headaches that resist traditional treatments. As a minimally invasive option with limited side effects, RFA may reduce the need for ongoing pharmacologic management and improve the quality of life for chronic headache sufferers.

Background: Inherited white matter (WM) disorders of the central nervous systems (CNS), or leukodystrophies, are devastating diseases that primarily affect children, many of whom die early in life or suffer from long-term disability. Methods: q-Space diffusion MR imaging (QSI) and diffusion tensor MR imaging (DTI) with the same resolution and timing parameters were used to study the spinal cords (SCs) of two myelin mutants that are experimental models of WM diseases of different severity, namely the 28-day-old taiep and Long–Evans Shaker (les) rats. The aim was to verify if and which of the diffusion methodologies used is more suitable for early detection of the milder taiep pathology and to characterize its early phase. We also aimed to compare the diffusion MRI results with quantitative electron microscopy (EM) findings. Results: We found that at this early age (28 days), both QSI and DTI were able to detect the severe les WM pathology, while the milder WM pathology in the SC of the taiep rats was detected only by QSI. An increase in the mean radial displacement (RaDis), representing the MRI axon diameter (AD), and a decrease in the probability for zero displacement (PZD) were observed in the dorsal column (ROI 1) of the taiep SCs. In other WM areas, the same trends were observed but the differences were not of statistical significance. In DTI, we found some lower fractional anisotropy (FA) values in the taiep SCs compared to the controls; however, these differences were not statistically significant. For the more severe les pathology, we observed a dramatic increase in the RaDis values and a large decrease in PZD values in all ROIs examined. There, even the FA values were lower than that of the control SCs in all ROIs, albeit with much smaller statistical significance. These MRI results, which show a higher detectability of WM pathology with heavier diffusion weighting, followed histological findings that showed significant myelin deficiency in the dorsal column in the taiep SCs and a practically complete myelin loss in all WM areas in the les SCs. This study also revealed that, under the experimental conditions used here, the apparent increase in RaDis agrees better with myelin thickness and not with average AD extracted form EM, probably reflecting the effect of water exchange. Conclusions: These results, corroborated by diffusion time-dependent QSI, also imply that while diffusion MRI in general and QSI in particular provide acceptable apparent axon diameter estimations in heathy and mature WM, this appears not to be the case in severely damaged WM where exchange appears to play a more important role.