A brainstem maestro conducting the somatic and autonomic motor symphony.

Somatic and sympathetic tones fluctuate together seamlessly across daily behaviors. In this issue of Cell, Zhang et al. describe populations of spinal projecting neurons in the rostral ventromedial medulla (rVMM) that harmonize somatic motor function and sympathetic activation. The coordinated regulation plays a vital role in supporting behaviors associated with various arousal states.

Distinct involvement of the cranial and spinal nerves in progressive supranuclear palsy.

The most frequent neurodegenerative proteinopathies include diseases with deposition of misfolded tau or α-synuclein in the brain. Pathological protein aggregates in the PNS are well-recognized in α-synucleinopathies and have recently attracted attention as a diagnostic biomarker. However, there is a paucity of observations in tauopathies. To characterize the involvement of the PNS in tauopathies, we investigated tau pathology in cranial and spinal nerves (PNS-tau) in 54 tauopathy cases [progressive supranuclear palsy (PSP), n = 15; Alzheimer's disease (AD), n = 18; chronic traumatic encephalopathy (CTE), n = 5; and corticobasal degeneration (CBD), n = 6; Pick's disease, n = 9; limbic-predominant neuronal inclusion body 4-repeat tauopathy (LNT), n = 1] using immunohistochemistry, Gallyas silver staining, biochemistry, and seeding assays. Most PSP cases revealed phosphorylated and 4-repeat tau immunoreactive tau deposits in the PNS as follows: (number of tau-positive cases/available cases) cranial nerves III: 7/8 (88%); IX/X: 10/11 (91%); and XII: 6/6 (100%); anterior spinal roots: 10/10 (100%). The tau-positive inclusions in PSP often showed structures with fibrillary (neurofibrillary tangle-like) morphology in the axon that were also recognized with Gallyas silver staining. CBD cases rarely showed fine granular non-argyrophilic tau deposits. In contrast, tau pathology in the PNS was not evident in AD, CTE and Pick's disease cases. The single LNT case also showed tau pathology in the PNS. In PSP, the severity of PNS-tau involvement correlated with that of the corresponding nuclei, although, occasionally, p-tau deposits were present in the cranial nerves but not in the related brainstem nuclei. Not surprisingly, most of the PSP cases presented with eye movement disorder and bulbar symptoms, and some cases also showed lower-motor neuron signs. Using tau biosensor cells, for the first time we demonstrated seeding capacity of tau in the PNS. In conclusion, prominent PNS-tau distinguishes PSP from other tauopathies. The morphological differences of PNS-tau between PSP and CBD suggest that the tau pathology in PNS could reflect that in the central nervous system. The high frequency and early presence of tau lesions in PSP suggest that PNS-tau may have clinical and biomarker relevance.

Spinal nerve transection-induced upregulation of SAP97 via promoting membrane trafficking of GluA1-containing AMPA receptors in the dorsal horn contributes to the pathogenesis of neuropathic pain.

Emerging evidence has implicated an important role of synapse-associated protein-97 (SAP97)-regulated GluA1-containing AMPARs membrane trafficking in cocaine restate and in contextual episodic memory of schizophrenia. Herein, we investigated the role of SAP97 in neuropathic pain following lumbar 5 spinal nerve transection (SNT) in rats. Our results showed that SNT led to upregulation of SAP97, enhanced the interaction between SAP97 and GluA1, and increased GluA1-containing AMPARs membrane trafficking in the dorsal horn. Microinjection of AAV-EGFP-SAP97 shRNA in lumbar 5 spinal dorsal horn inhibited SAP97 production, decreased SAP97-GluA1 interaction, reduced the membrane trafficking of GluA1-containing AMPARs, and partially attenuated neuropathic pain following SNT. Intrathecal injections of SAP97 siRNA or NASPM, an antagonist of GluA1-containing AMPARs, also partially reversed neuropathic pain on day 7, but not on day 14, after SNT. Spinal overexpression of SAP97 by AAV-EGFP-SAP97 enhanced SAP97-GluA1 interaction, increased the membrane insertion of GluA1-containing AMPARs, and induced abnormal pain in naïve rats. In addition, treatment with SAP97 siRNA or NASPM i.t. injection alleviated SNT-induced allodynia and hyperalgesia and exhibited a longer effect in female rats. Together, our results indicate that the SNT-induced upregulation of SAP97 via promoting GluA1-containing AMPARs membrane trafficking in the dorsal horn contributes to the pathogenesis of neuropathic pain. Targeting spinal SAP97 might be a promising therapeutic strategy to treatment of chronic pain.

Grape seed-derived procyanidins decreases neuropathic pain and nerve regeneration by suppression of toll-like receptor 4-myeloid differentiation factor-88 signaling.

Background: Recent studies have shown that peripheral nerve regeneration process is closely related to neuropathic pain. Toll-like receptor 4 (TLR4) signaling was involved in different types of pain and nerve regeneration. TLR4 induced the recruitment of myeloid differentiation factor-88 adaptor protein (MyD88) and NF-κB-depended transcriptional process in sensory neurons and glial cells, which produced multiple cytokines and promoted the induction and persistence of pain. Our study aimed to investigate procyanidins's effect on pain and nerve regeneration via TLR4-Myd88 signaling. Methods: Spinal nerve ligation (SNL) model was established to measure the analgesic effect of procyanidins. Anatomical measurement of peripheral nerve regeneration was measured by microscopy and growth associated protein 43 (GAP43) staining. Western blotting and/or immunofluorescent staining were utilized to detect TLR4, myeloid differentiation factor-88 adaptor protein (MyD88), ionized calcium-binding adapter molecule 1 (IBA1) and nuclear factor kappa-B-p65 (NF-κB-p65) expression, as well as the activation of astrocyte and microglia. The antagonist of TLR4 (LPS-RS-Ultra, LRU) were intrathecally administrated to assess the behavioral effects of blocking TLR4 signaling on pain and nerve regeneration. Result: Procyanidins reduced mechanical allodynia, thermal hyperalgesia and significantly suppressed the number of nerve fibers regenerated and the degree of myelination in SNL model. Compared with sham group, TLR4, MyD88, IBA1 and phosphorylation of NF-κB-p65 were upregulated in SNL rats which were reversed by procyanidins administration. Additionally, procyanidins also suppressed activation of spinal astrocytes and glial cells. Conclusion: Suppression of TLR4-MyD88 signaling contributes to the alleviation of neuropathic pain and reduction of nerve regeneration by procyanidins.

Spinal nerve transection-induced upregulation of KDM4A in the dorsal root ganglia contributes to the development and maintenance of neuropathic pain via promoting CCL2 expression in rats.

Studies indicate that the lysine-specific demethylase 4A (KDM4A), acts as a key player in neuropathic pain, driving the process through its involvement in promoting neuroinflammation. Emerging evidence reveals that C-C Motif Chemokine Ligand 2 (CCL2) participates in neuroinflammation, which plays an important role in the development and maintenance of neuropathic pain. However, it remains unclear if KDM4A plays a role in regulating CCL2 in neuropathic pain. This study found that following spinal nerve transection (SNT) of the lumbar 5 nerve root in rats, the expression of KDM4A and CCL2 increased in the ipsilateral L4/5 dorsal root ganglia (DRG). Injecting KDM4A siRNA into the DRGs of rats post-SNT resulted in a higher paw withdrawal threshold (PWT) and paw-withdrawal latency (PWL) compared to the KDM4A scRNA group. In addition, prior microinjection of AAV-EGFP-KDM4A shRNA also alleviates the decrease in PWT and PWL caused by SNT. Correspondingly, microinjection of AAV-EGFP-KDM4A shRNA subsequent to SNT reduced the established mechanical and thermal hyperalgesia. Furthermore, AAV-EGFP-KDM4A shRNA injection decreased the expression of CCL2 in DRGs. ChIP-PCR analysis revealed that increased binding of p-STAT1 with the CCL2 promoter induced by SNT was inhibited by AAV-EGFP-KDM4A shRNA treatment. These findings suggest that KDM4A potentially influences neuropathic pain by regulating CCL2 expression in DRGs.

Correspondence: Morphological features of the greater occipital nerve and its possible importance for interventional procedures.

This response applauds Saglam et al.'s (2023) recent study on the greater occipital nerve's anatomy while urging readers to consider earlier pivotal studies overlooked. It emphasizes how prior research has significantly shaped headache treatments and provides valuable insights for future practices and discussions.

Morphological features of the greater occipital nerve and its possible importance for interventional procedures.

Being one of the most prevalent neurological symptoms, headaches are burdensome and costly. Blocks and decompression surgeries of the greater occipital nerve (GON) have been frequently used for migraine, cervicogenic headache, and occipital neuralgia which are classified under headache by International Headache Society. Knowledge of complex anatomy of GON is crucial for its decompression surgery and block. This study was performed to elucidate anatomical features of this nerve in detail. Forty-one cadavers were dissected bilaterally. According to its morphological features, GON was classified into four main types that included 18 subtypes. Moreover, potential compression points of the nerve were defined. The number of branches of the GON up to semispinalis capitis muscle and the number of its branches that were sent to this muscle were recorded. The most common variant was that the GON pierced the aponeurosis of the trapezius muscle, curved around the lower edge of the obliquus capitis inferior muscle, and was loosely attached to the obliquus capitis inferior muscle (Type 2; 61 sides, 74.4%). In the subtypes, the most common form was Type 2-A (44 sides, 53.6%), in which the GON pierced the aponeurosis of each of the trapezius muscle and fibers of semispinalis muscle at one point and there was a single crossing of the GON and occipital artery. Six potential compression points of the GON were detected. The first point was where the nerve crossed the lower border of the obliquus capitis inferior muscle. The second and third points were at its piercing of the semispinalis capitis muscle and the muscle fibers/aponeurosis of the trapezius, respectively. Fourth, fifth, and sixth compression points of GON were located where the GON and occipital artery crossed each other for the first, second, and third times, respectively. On 69 sides, 1-4 branches of the GON up to the semispinalis capitis muscle were observed (median = 1), while 1-4 branches of GON were sent to the semispinalis capitis muscle on 67 sides (median = 1). The novel anatomical findings described in this study may play a significant role in increasing the success rate of invasive interventions related with the GON.

Upregulation of Spinal MDGA1 in Rats After Nerve Injury Alters Interactions Between Neuroligin-2 and Postsynaptic Scaffolding Proteins and Increases GluR1 Subunit Surface Delivery in the Spinal Cord Dorsal Horn.

Previous studies suggested that postsynaptic neuroligin-2 may shift from inhibitory toward excitatory function under pathological pain conditions. We hypothesize that nerve injury may increase the expression of spinal MAM-domain GPI-anchored molecule 1 (MDGA1), which can bind to neuroligin-2 and thereby, alter its interactions with postsynaptic scaffolding proteins and increase spinal excitatory synaptic transmission, leading to neuropathic pain. Western blot, immunofluorescence staining, and co-immunoprecipitation studies were conducted to examine the critical role of MDGA1 in the lumbar spinal cord dorsal horn in rats after spinal nerve ligation (SNL). Small interfering ribonucleic acids (siRNAs) targeting MDGA1 were used to examine the functional roles of MDGA1 in neuropathic pain. Protein levels of MDGA1 in the ipsilateral dorsal horn were significantly upregulated at day 7 post-SNL, as compared to that in naïve or sham rats. The increased levels of GluR1 in the synaptosomal membrane fraction of the ipsilateral dorsal horn tissues at day 7 post-SNL was normalized to near sham level by pretreatment with intrathecal MDGA1 siRNA2308, but not scrambled siRNA or vehicle. Notably, knocking down MDGA1 with siRNAs reduced the mechanical and thermal pain hypersensitivities, and inhibited the increased excitatory synaptic interaction between neuroligin-2 with PSD-95, and prevented the decreased inhibitory postsynaptic interactions between neuroligin-2 and Gephyrin. Our findings suggest that SNL upregulated MDGA1 expression in the dorsal horn, which contributes to the pain hypersensitivity through increasing the net excitatory interaction mediated by neuroligin-2 and surface delivery of GluR1 subunit in dorsal horn neurons.

Optogenetic activation of spinal microglia triggers chronic pain in mice.

Spinal microglia are highly responsive to peripheral nerve injury and are known to be a key player in pain. However, there has not been direct evidence showing that selective microglial activation in vivo is sufficient to induce chronic pain. Here, we used optogenetic approaches in microglia to address this question employing CX3CR1creER/+: R26LSL-ReaChR/+ transgenic mice, in which red-activated channelrhodopsin (ReaChR) is inducibly and specifically expressed in microglia. We found that activation of ReaChR by red light in spinal microglia evoked reliable inward currents and membrane depolarization. In vivo optogenetic activation of microglial ReaChR in the spinal cord triggered chronic pain hypersensitivity in both male and female mice. In addition, activation of microglial ReaChR up-regulated neuronal c-Fos expression and enhanced C-fiber responses. Mechanistically, ReaChR activation led to a reactive microglial phenotype with increased interleukin (IL)-1ß production, which is likely mediated by inflammasome activation and calcium elevation. IL-1 receptor antagonist (IL-1ra) was able to reverse the pain hypersensitivity and neuronal hyperactivity induced by microglial ReaChR activation. Therefore, our work demonstrates that optogenetic activation of spinal microglia is sufficient to trigger chronic pain phenotypes by increasing neuronal activity via IL-1 signaling.

Segmental infralesional pathological spontaneous activity in subacute traumatic spinal cord injury.

INTRODUCTION/AIMS: There is a dearth of knowledge regarding the status of infralesional lower motor neurons (LMNs) in individuals with traumatic cervical spinal cord injury (SCI), yet there is a growing need to understand how the spinal lesion impacts LMNs caudal to the lesion epicenter, especially in the context of nerve transfer surgery to restore several key upper limb functions. Our objective was to determine the frequency of pathological spontaneous activity (PSA) at, and below, the level of spinal injury, to gain an understanding of LMN health below the spinal lesion. METHODS: Ninety-one limbs in 57 individuals (53 males, mean age = 44.4 ± 16.9 years, mean duration from injury = 3.4 ± 1.4 months, 32 with motor complete injuries), were analyzed. Analysis was stratified by injury level as (1) C4 and above, (2) C5, and (3) C6-7. Needle electromyography was performed on representative muscles innervated by the C5-6, C6-7, C7-8, and C8-T1 nerve roots. PSA was dichotomized as present or absent. Data were pooled for the most caudal infralesional segment (C8-T1). RESULTS: A high frequency of PSA was seen in all infralesional segments. The pooled frequency of PSA for all injury levels at C8-T1 was 68.7% of the limbs tested. There was also evidence of PSA at the rostral border of the neurological level of injury, with 58.3% of C5-6 muscles in those with C5-level injuries. DISCUSSION: These data support a high prevalence of infralesional LMN abnormalities following SCI, which has implications to nerve transfer candidacy, timing of the intervention, and donor nerve options.

Clinical predictors of therapeutic failure of occipital nerve stimulation in refractory chronic cluster headache.

BACKGROUND: Occipital nerve stimulation (ONS) is a treatment with evidence in refractory chronic cluster headache (CCH). However, the variable response rate and cost make it necessary to investigate predictors of response. METHODS: This is a cross-sectional study conducted through the review of medical records of CCH patients from six hospitals in Madrid. Epidemiological and clinical variables were compared between patients with ONS failure and the rest. ONS failure was defined as the need for device withdrawal or switch off because of lack of response or adverse events. RESULTS: From a series of 88 CCH, 26 (29.6%) underwent ONS surgery, of whom 13/26 (50.0%) failed because lack of response. ONS failure group had an earlier headache onset (mean ± SD) of 27.7 ± 6.9 vs. 36.7 ± 11.8 years, p = 0.026) and a higher smoking rate (100% vs. 42.9%, p = 0.006). Stational fluctuations (58.3% vs. 7.7%, p = 0.007) and nocturnal exacerbations (91.7% vs. 53.9%, p = 0.035) were more frequent in the ONS failure group as well. There was no difference between groups in diagnostic delay, years of evolution prior to surgery, mental illness, comorbidity with other headache disorders or chronic pain conditions or prior response to occipital nerves anesthetic blocks. CONCLUSIONS: Some clinical features such as an early debut, smoking and seasonal or circadian fluctuations could be related to failure of ONS in refractory CCH.

An anatomical analysis of the occipital nerve complex: an essential tool for the application of occipital nerve blocks.

BACKGROUND: Occipital nerve blocks are essential in diagnosing and treating headache disorders such as migraine, cervicogenic headache, occipital neuralgia, and cluster headache. In this study, we aimed to investigate the potential compression points of the greater occipital nerve (GON), third occipital nerve (TON), and lesser occipital nerve (LON) which are targeted to block in occipital nerve blocks and to develop a method to detect these points easily. METHODS: To identify potential compression points of the GON, TON, and LON, we dissected 43, 41, and 26 cadavers, respectively. A rigid, transparent tool divided into 1 × 1 cm sections was placed on the external occipital protuberance to measure the determined points. The cadaveric head was viewed from above, vertically, and the coordinates corresponding to each point were noted separately. RESULTS: Six, four, and one potential entrapment points were detected for the GON, TON, and LON, respectively. The distances of the point where the GON arose from the lower border of the obliquus capitis inferior muscle and the emerging point of the TON from the C2-C3 vertebrae to the posterior midline were statistically significant in terms of the sides (p = 0.040). Similarly, there was a statistical significance between genders for the distance of the point where the LON arose from the posterior edge of the sternocleidomastoid muscle to the posterior midline (p = 0.002). CONCLUSIONS: We believe that with the method developed, the GON, TON, and LON compression points can be easily localized and blocked in diagnosing and treating patients experiencing headaches such as migraines, cervicogenic headaches, occipital neuralgia, and cluster headache.

Comparison of two methods of greater occipital nerve block in patients with chronic migraine: ultrasound-guided and landmark-based techniques.

BACKGROUND: Migraine is a primary headache defined as moderate-to-severe pain lasting 4 to 72 h, ranking 2nd among the disabling conditions for both genders regardless of the age and the greater occipital nerve (GON) block has been reported as an efficient treatment method for migraine. The present study aims to evaluate and compare the efficiency of the two methods of GON block, i.e., the ultrasound (US)-guided technique and the landmark-based technique. METHOD: Having a prospective and randomized design, the study assigned the patients with chronic migraine into two groups after which a neurologist performed landmark-based GON block in the first group while an algologist performed US-guided GON block in the second group. During the 3-month follow-up period, the number of days with pain, the duration of pain, the number of analgesic drugs taken in a month, and Visual Analogue Scale (VAS) scores were compared with the values ​​before treatment and at the 1st week, 1st month, and 3rd month after treatment. RESULTS: US-guided GON block group included 34 patients while there were 32 patients in the landmark-based GON block group. US-guided GON block group showed significantly reduced VAS scores and frequency of attacks compared to the landmark-based GON block group at Month 1 after the procedure. After a 3-month follow-up period of the two groups, the frequency of attacks, analgesic intake and the duration of attacks were lower in both groups compared to the baseline. At 3-month follow-up, the mean of VAS scores decreased from 9,47 ± 2,69 to 4,67 ± 1,9 in US-guided GON block group and from 9,46 ± 0,98 to 7 ± 2,5 in the landmark-based GON block group. CONCLUSION: It was determined that both US-guided and landmark-based GON block were efficient techniques in patients with chronic migraine. US-guided GON block technique resulted in lower VAS scores, shorter durations of pain, lower frequencies of attack, and lower intake of analgesics compared to the landmark-based GON block technique.

Combined antiallodynic effects of Neurotropin®-tramadol and Neurotropin®-mirogabalin in rats with L5-spinal nerve ligation.

We aimed to examine the efficacy of combination therapies of Neurotropin® with tramadol and Neurotropin with mirogabalin for neuropathic pain management. A neuropathic pain model (L5 spinal nerve ligation model: L5-SNL) using male Wistar rats was generated through tight ligation of the left fifth lumbar nerve using silk sutures. Mechanical allodynia was assessed using the 50% paw withdrawal threshold. The combined antiallodynic effects were evaluated using isobolographic analyses. Small intestinal transit was evaluated using the charcoal meal test, and motor coordination using the rota-rod test. Neurotropin (50-200 NU/kg, p.o.), tramadol (7.5-60 mg/kg, p.o.), and mirogabalin (3-30 mg/kg, p.o.) showed a dose-dependent antiallodynic effect in L5-SNL rats. The combined antiallodynic effects of Neurotropin and tramadol were additive or synergistic, whereas those of Neurotropin and mirogabalin were additive. Neurotropin (100-400 NU/kg, p.o.) did not affect the small intestinal transit, whereas tramadol (30-100 mg/kg, p.o.) significantly inhibited it. Neurotropin (100-400 NU/kg, p.o.) did not affect the walking time, whereas mirogabalin (10-100 mg/kg, p.o.) significantly decreased it. Neurotropin dose-dependently ameliorated mechanical allodynia in rats, and combination therapy with Neurotropin-tramadol or Neurotropin-mirogabalin may alleviate neuropathic pain without aggravating the adverse effects of tramadol and mirogabalin.

Review of craniofacial pain syndromes involving the greater occipital nerve: relevant anatomy, clinical findings, and interventional management.

Craniofacial pain syndromes exhibit a high prevalence in the general population, with a subset of patients developing chronic pain that significantly impacts their quality of life and results in substantial disabilities. Anatomical and functional assessments of the greater occipital nerve (GON) have unveiled its implication in numerous craniofacial pain syndromes, notably through the trigeminal-cervical convergence complex. The pathophysiological involvement of the greater occipital nerve in craniofacial pain syndromes, coupled with its accessibility, designates it as the primary target for various interventional procedures in managing craniofacial pain syndromes. This educational review aims to describe multiple craniofacial pain syndromes, elucidate the role of GON in their pathophysiology, detail the relevant anatomy of the greater occipital nerve (including specific intervention sites), highlight the role of imaging in diagnosing craniofacial pain syndromes, and discuss various interventional procedures such as nerve infiltration, ablation, neuromodulation techniques, and surgeries. Imaging is essential in managing these patients, whether for diagnostic or therapeutic purposes. The utilization of image guidance has demonstrated an enhancement in reproducibility, as well as technical and clinical outcomes of interventional procedures. Studies have shown that interventional management of craniofacial pain is effective in treating occipital neuralgia, cervicogenic headaches, cluster headaches, trigeminal neuralgia, and chronic migraines, with a reported efficacy of 60-90% over a duration of 1-9 months. Repeated infiltrations, neuromodulation, or ablation may prove effective in selected cases. Therefore, reassessment of treatment response and efficacy during follow-up is imperative to guide further management and explore alternative treatment options. Optimal utilization of imaging, interventional techniques, and a multidisciplinary team, including radiologists, will ensure maximum benefit for these patients.

Picroside â ¡ attenuates neuropathic pain by regulating inflammation and spinal excitatory synaptic transmission.

Nerve injury induced microglia activation, which released inflammatory mediators and developed neuropathic pain. Picroside Ⅱ (PⅡ) attenuated neuropathic pain by inhibiting the neuroinflammation of the spinal dorsal horn; however, how it engaged in the cross talk between microglia and neurons remained ambiguous. This study aimed to investigate PⅡ in the modulation of spinal synaptic transmission mechanisms on pain hypersensitivity in neuropathic rats. We investigated the analgesia of PⅡ in mechanical and thermal hyperalgesia using the spinal nerve ligation (SNL)-induced neuropathic pain model and formalin-induced tonic pain model, respectively. RNA sequencing and network pharmacology were employed to screen core targets and signaling pathways. Immunofluorescence staining and qPCR were performed to explore the expression level of microglia and inflammatory mediator mRNA. The whole-cell patch-clamp recordings were utilized to record miniature excitatory postsynaptic currents in excitatory synaptic transmission. Our results demonstrated that the analgesic of PⅡ was significant in both pain models, and the underlying mechanism may involve inflammatory signaling pathways. PⅡ reversed the SNL-induced overexpression of microglia and inflammatory factors. Moreover, PⅡ dose dependently inhibited excessive glutamate transmission. Thus, this study suggested that PⅡ attenuated neuropathic pain by inhibiting excitatory glutamate transmission of spinal synapses, induced by an inflammatory response on microglia.

Four Decades of Occipital Nerve Stimulation for Headache Disorders: A Systematic Review.

PURPOSE OF REVIEW: Chronic headaches are a significant source of disability worldwide. Despite the development of conventional strategies, a subset of patients remain refractory and/or experience side effects following these treatments. Hence, occipital nerve stimulation (ONS) should be considered as an alternative strategy for intractable chronic headaches. This review aims to provide a comprehensive overview of the effectiveness, safety, mechanisms and practical application of ONS for the treatment of headache disorders. RECENT FINDINGS: Overall response rate of ONS is 35.7-100%, 17-100%, and 63-100% in patients with cluster headache, chronic migraine and occipital neuralgia respectively. Regarding the long-term effectivity in all groups, 41.6-88.0% of patients remain responders after ≥ 18.3 months. The most frequently reported adverse events include lead migration/fracture (13%) and local pain (7.3%). Based on our results, ONS can be considered a safe and effective treatment for chronic intractable headache disorders. To support more widespread application of ONS, additional research with larger sample sizes should be conducted.

Mitigating Factors in L4 and L5 Medial Branch Motor Stimulation During Radiofrequency Ablation.

PURPOSE OF REVIEW: Radiofrequency ablation (RFA) is a minimally invasive procedure for facet joint pain. The targets for the procedure are the medial branches of the dorsal spinal nerves which innervate the facet joints. Before RFA, patients undergo diagnostic meal branch blocks to ensure appropriate pain relief and confirm the utility of proceeding to RFA. The success of RFA relies heavily on procedural technique and accurate placement near the medial branch. RECENT FINDINGS: Motor testing is utilized in the lumbar region to assess the response of the multifidus and ensure proper placement of the RFA probe to prevent inadvertent damage to surrounding spinal anatomy. However, relying on motor responses in this area presents challenges given the frequency of lack of muscle twitching. Factors contributing to limited muscle twitch responses include muscle atrophy, excessive lordosis, facet arthropathy, local anesthetic use before ablation, and previous surgical neurotomy. These complexities highlight the challenges in ensuring precise motor stimulation during RFA. Despite these obstacles, accurate anatomical placement remains crucial. For RFA cases that prove challenging, relying on anatomical placement can be adequate to proceed with the procedure. Bridging knowledge gaps is vital for standardized practices and safer procedures. Further research is necessary to refine techniques, understand patient-specific factors, and enhance the efficacy of RFA in managing chronic lumbar facet joint pain.

Comparison of the Efficacy of Different Radiofrequency Techniques for the Treatment of Lumbar Facet Joint Pain: Combined with Anatomy.

PURPOSE OF REVIEW: Lumbar facet pain is generally considered to be one of the major causes of chronic low back pain. Each lumbar facet joint is innervated by the medial branch of the posterior spinal nerve from its own level and above. Radiofrequency (RF) of the medial branch of the posterior branch of the spinal nerve is an effective method for the treatment of lumbar facet pain. RF technology is diverse, including traditional radiofrequency (TRF), pulsed radiofrequency (PRF), cooled radiofrequency (CRF), low-temperature plasma radiofrequency ablation (CA), and other treatment methods. The purpose of this paper is to compare the efficacy of different radiofrequency techniques and to analyze the reasons for this in the context of anatomy. RECENT FINDINGS: There have been studies confirming the differences in efficacy of different RF techniques. However, most of the studies only compared two RF techniques, not four techniques, TRF, CRF, PRF, and CA, and did not analyze the reasons for the differences in efficacy. This article reviews the differences in the efficacy of the above four RF techniques, clarifies that the differences are mainly due to the inability to precisely localize the medial branch of the posterior branch of the spinal nerve, analyzes the reasons for the inability to precisely localize the posterior branch of the spinal nerve in conjunction with anatomy, and proposes that the development of RF technology for lumbar facet pain requires more in-depth anatomical, imaging, and clinical studies.

Occipital nerve stimulation in pediatric patients with refractory occipital neuralgia.

PURPOSE: Occipital neuralgia (ON) is a disabling problem within the pediatric population. Many of these patients fail medical therapies and continue to suffer without further surgical management. Occipital nerve stimulation (ONS) is used to treat ON in the adult population leading to a 72-89% reduction in pain; however, there are limited studies regarding its use in the pediatric population. In this study, we examined the outcomes of ONS in pediatric patients with medically refractory ON. METHODS: We performed a chart review of pediatric patients at our institution who have undergone ONS for the same indications. RESULTS: We identified 3 patients at our institution who underwent ONS trial and/or permanent implantation for ON. One patient had complete pain relief after the trial and declined permanent implantation. The other patient had fewer attacks compared to his pre-trial baseline and controlled them by adjusting his permanent implant stimulation settings. The last patient had near complete relief of her symptoms and no longer required any pain medication. CONCLUSION: Our study highlights the paucity of studies evaluating the utility of ONS in the pediatric ON population. Limited data from both the literature and our institution's experience reveal that pediatric patients may benefit from trial and/or permanent implantation of ONS for medically refractory ON pain.