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.
METHODS: 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.
CONCLUSIONS: 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.

UNASSIGNED: Migraine headaches are a significant global health concern, frequently managed with varying levels of success. Compression of the greater occipital nerve (GON) is hypothesized to contribute to pathology in some migraine patients, making extracranial nerve decompression surgery a potential intervention for refractory cases. However, accurate methods to image the GON along its tortuous course still need to be explored. Our group has developed magnetic resonance imaging sequences to track the GON. Yet, many challenges were met, which included navigating the GON\'s complex anatomy, understanding anatomical variants, and designing advanced magnetic resonance imaging sequences and coils to image the posterior scalp. Addressing these hurdles is vital to capture and understand GON pathology and guide potential interventions.

OBJECTIVE: Greater occipital nerve (GON) blockade injections can be used to prevent episodic and chronic cluster headaches. In recent studies, prophylactic treatment has been used in addition to the GON blockade. In this study, we aimed to elucidate the effect of GON blockade on the attack frequency, pain intensity, and duration in patients diagnosed with chronic cluster headaches.
METHODS: The demographic characteristics of 30 patients who received GON blockade along with acute attack treatment, short- and long-term prophylactic treatment for cluster headache, and 24 patients who received only acute attack treatment, short- and long-term prophylactic treatment, before blockade treatment, in the 1st week and 1st month after blockade were investigated. Attack frequency, attack duration, and visual analog scale (VAS) variables were compared.
RESULTS: We evaluated the VAS score, daily attack frequency, and duration of pain attacks after repeated GON blockade and found a statistically significant difference in the VAS score, daily attack frequency, duration of pain attacks, average values of the treatment, and time interaction of pain intensity in the group in which GON blockade was applied in the 1st week and 1st month compared to the pre-treatment period (p<0.01), (p<0.01), (p=0.044).
CONCLUSIONS: Regarding the outcomes of this research, GON blockade provided significant improvement in pain frequency, attack duration, and VAS score in the period from attack treatment to the start of long-term prophylaxis treatment and one month after treatment, without the need to switch to different prophylaxis treatments. Therefore, GON blockade may be a preferable and reliable treatment option.

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.

BACKGROUND: Cluster headache (CH) is a significant health concern due to its major socioeconomic consequences and most patients being refractory to conventional strategies. For treatment resistant CH, occipital nerve stimulation (ONS) is considered an effective treatment option. Whereas most patients do not adjust the amplitude of the ONS system, a subset changes the amplitude on a regular basis using their remote control, and are therefore referred to as \'voltage tuners\'. Anxiety and self-control are thought to be central themes to this behavior. Research on this voltage tuning behavior could provide new insights in the use of ONS as acute attack treatment. To date, voltage tuning has not been assessed for CH. Hence this is a unique study aiming to investigate the occurrence and efficacy of voltage tuning in patients with CH and ONS.
METHODS: For this analysis, patients with CH who received ONS from 2020-2024, at our university medical center, were included. All patients underwent bilateral ONS implantation. Data on attack frequency, intensity and duration were collected retrospectively. Outcomes on the response, frequency, moment during the day, duration, rationale, sensation, average increase in amplitude, and efficacy of voltage tuning were collected with prospective interviews.
RESULTS: Thirty-three patients (M = 20) (42 ± 12.7 years) were included in the current analysis. At 1y follow-up, an overall response rate of 70% (23/33) was found for ONS. In total, 48% (18/33) of patients were defined as voltage tuners. Voltage tuning was performed with an average increase in amplitude of 92 (20-360)%, a frequency of 1-20 times/month and duration of 20 minutes-48 hours. Sensations of voltage tuning were described as \"tingling\" and/or \"pinching\". The rationale for voltage tuning in patients varied from prevention and ceasing to lowering the intensity and enhance control of CH attack.
CONCLUSIONS: Outcomes show that voltage tuning may cease and/or terminate CH attacks and therefore raise interests in the use of ONS as acute attack treatment for patients with resistant CH treated with ONS. Future research on the occurrence and potential of voltage tuning will provide valuable insights for achieving optimal efficacy of ONS and quality of life in patients with CH.

Aim: To describe the successful treatment of atypical occipital neuralgia (ON) using a unilateral dual-lead occipital nerve stimulator.Setting: Outpatient clinic/operating room.Patient: A 53-year-old male with atypical ON.Case description: Patient was previously diagnosed with treatment-refractory left-sided trigeminal neuralgia with atypical occipital distribution. On presentation, his symptoms were consistent with ON with distribution to the left fronto-orbital area. He received a left-sided nerve stimulator implant targeting both the greater and lesser occipital nerves.Results: Patient reported pain relief from a numerical rating scale 10/10 to 3-4/10.Conclusion: ON with referred ipsilateral trigeminal distribution should be considered when patients present with simultaneous facial and occipital pain. Further, a dual-lead unilateral stimulator approach may be a viable treatment.
Atypical, persistent inflammation to the left occipital nerve treated with a neuromodulator: a case reportAim: To describe the successful treatment of atypical headache using a one-sided nerve stimulator.Setting: Outpatient clinic/operating room.Patient: A 53-year-old male with atypical headache.Case description: Patient was previously diagnosed with left-sided chronic facial pain with pain to the back of the head. He previously failed to improve with medication and underwent Botox injections and several surgical operations targeting the nerves responsible for his pain symptoms with no improvement. He recently underwent a nerve-stimulating device trial, designed to alter the activity levels of the targeted nerve, that targeted a nerve in the back of his head. This significantly improved his pain and he ultimately presented for an official stimulator implant. Upon presentation, his symptoms were consistent with left-sided headache to the back of the head with distribution to the left eye area.Results: Patient reported significant pain relief from 10/10 to a 3-4/10, with a 10 representing the worst pain the patient has ever felt.Conclusion: Left-sided headache on the back of the head that can distribute to the left eye area should be a consistent thought for pain/headache practitioners. Further, this stimulator placement approach may be a viable treatment.

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.

BACKGROUND: This study analyzed the etiologies and treatment of iatrogenic occipital nerve injuries.
METHODS: Patients with occipital neuralgia (ON) who were screened for occipital nerve decompression surgery were prospectively enrolled. Patients with iatrogenic occipital nerve injuries who underwent nerve decompression surgery were identified. Data included surgical history, pain characteristics, and surgical technique. Outcomes included pain frequency (days/month), duration (h/day), intensity (0-10), migraine headache index (MHI), and patient-reported percent-resolution of pain.
RESULTS: Among the 416 patients with ON, who were screened for occipital nerve decompression surgery, 12 (2.9%) cases of iatrogenic occipital nerve injury were identified and underwent surgical treatment. Preoperative headache frequency was 30 (±0.0) days/month, duration was 19.4 (±6.9) h, and intensity was 9.2 (±0.9). Neuroma excision was performed in 5 cases followed by targeted muscle reinnervation in 3, nerve cap in 1, and muscle burial in 1. In patients without neuromas, greater occipital nerve decompression and/or lesser occipital nerve neurectomy were performed. At the median follow-up of 12 months (IQR 12-12 months), mean pain frequency was 4.0 (±6.6) pain days/month (p < 0.0001), duration was 6.3 (±8.9) h (p < 0.01), and intensity was 4.4 (±2.8) (p < 0.001). Median patient-reported resolution of pain was 85% (56.3%-97.5%) and success rate was (≥50% MHI improvement) 91.7%.
CONCLUSIONS: Iatrogenic occipital nerve injuries can be caused by various surgical interventions, including craniotomies, cervical spine interventions, and scalp tumor resections. The associated pain can be severe and chronic. Iatrogenic ON should be considered in the differential diagnosis of post-operative headaches and can be treated with nerve decompression surgery or neuroma excision with reconstruction of the free nerve end.

Occipital nerve decompression is effective in reducing headache symptoms in select patients with migraine and occipital neuralgia. Eligibility for surgery relies on subjective symptoms and responses to nerve blocks and Onabotulinum toxin A (Botox) injections. No validated objective method exists for detecting occipital headache pathologies. The purpose of the study is to explore the potential of high-resolution Magnetic Resolution Imaging (MRI) in identifying greater occipital nerve (GON) pathologies in chronic headache patients. The MRI protocol included three sequences targeting fat-suppressed fluid-sensitive T2-weighted signals. Visualization of the GON involved generating 2-D image slices with sequential rotation to track the nerve course. Twelve patients underwent pre-surgical MRI assessment. MRI identified four main pathologies that were validated against intra-operative examination: GON entanglement by the occipital artery, increased nerve thickness and hyperintensity suggesting inflammation compared to the non-symptomatic contralateral side, early GON branching with rejoining at a distal point, and a connection between the GON and the lesser occipital nerve. MRI possesses the ability to visualize the GON and identify suspected trigger points associated with headache symptoms. This case series highlights MRI\'s potential to provide objective evidence of nerve pathology. Further research is warranted to establish MRI as a gold standard for diagnosing extracranial contributors in headaches.

BACKGROUND: Neuropathic pain (NP) due to nerve injury, disrupts neural plasticity by triggering the release of inflammatory mediators. Alongside the hypothesis that neuro-inflammation contributes to this disruption, Andrographolide (Andro), a traditional bioactive compound derived from Andrographis paniculata, has garnered attention for its potent anti-inflammatory properties. However, whether Andro could ameliorate NP by regulating neuroinflammation remains unknown.
OBJECTIVE: This study aimed to investigate whether and how Andro regulates neuroinflammation and alleviates NP.
METHODS: The analgesic effects of Andro on NP were evaluated using both the spinal nerve ligation (SNL) and formalin rat models. A combination of network pharmacology, RNA sequencing, and experimental validation was employed to elucidate the underlying mechanism behind Andro\'s analgesic effects. Additionally, various techniques such as functional ultrasound, immunohistochemistry, quantitative real-time polymerase chain reaction (qPCR), patch clamp, and electron microscopy were employed to investigate the specific neural cell types, neural functions, and changes in neural plasticity influenced by Andro.
RESULTS: Network pharmacology analysis unveiled the crucial roles played by shared targets of Andro and pain in regulating pain-related inflammation, including microglia activation, neuroinflammation, immune modulation, and synaptic transmission. Furthermore, we confirmed Andro\'s superior efficacy in pain relief compared to the traditional analgesic drug, Gabapentin. In these models, Andro was observed to modulate the haemodynamic response triggered by SNL. Transcriptome analysis and molecular docking studies indicated the involvement of major histocompatibility complex class II (MHCII) genes (Db1, Da, and Bb). Electron microscopy revealed improvements in synaptic ultrastructure, and electrophysiological investigations showed a selective reduction in glutamatergic transmission in neuropathic rats after following Andro treatment. The integration of systems pharmacology analysis and biological validation collectively demonstrated that the mechanism of pain relief involves immune modulation, enhancement of synaptic plasticity, and precise regulation of excitatory neurotransmission.
CONCLUSIONS: In conclusion, this study has demonstrated that Andro, by targeting MHCII genes, may serve as a promising therapeutic candidate for neuropathic pain.