Approaches to Occipital Neuralgia Treatment: A Systematic Review and Case Examples

Abstract

Background:

Occipital neuralgia (ON) is a debilitating craniofacial pain disorder characterized by paroxysmal pain in the distribution of the greater, lesser, or third occipital nerves. Despite a growing array of interventions, clinical decision-making remains highly variable, with no standardized algorithm to guide diagnostic evaluation, procedural selection, or treatment escalation. Our objective was to synthesize the existing literature on ON management.

Methods:

A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines and registered with PROSPERO (International Prospective Register of Systematic Reviews). PubMed, Embase, and Scopus were searched from 2000 to 2025. Studies were assessed using AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews), SANRA (Scale for the Assessment of Narrative Review Articles), and AGREE II (Appraisal of Guidelines for Research and Evaluation) tools. A narrative synthesis was performed, and studies with decision frameworks were compared against our clinical approach.

Results:

Fourteen studies met the inclusion criteria, including 7 systematic reviews and 7 narrative reviews or guidelines. Most included diagnostic nerve blocks, decompression, neurectomy, and peripheral nerve stimulation; however, only a minority proposed structured algorithms. Our proposed framework integrates botulinum toxin stratification, nerve block response, imaging, and intraoperative findings to guide decompression versus neurectomy. A secondary escalation pathway addresses early versus late surgical failure and neuromodulation treatments.

Conclusions:

This review highlighted the need for unified, evidence-informed decision-making in ON. Our clinical approach offered a structured, patient-specific framework to guide diagnosis, treatment, and escalation, addressing key gaps in current practice.

Takeaways

Question: What is the optimal clinical pathway for diagnosing and surgically treating medically refractory occipital neuralgia, and how can diagnostic tools such as botulinum toxin response inform decision-making?

Findings: This systematic review synthesized 14 guidelines and review articles and presented a clinical framework combining physical examination, block response, imaging, and intraoperative findings. Two illustrative patient cases were provided to demonstrate real-world application of diagnostic stratification and tailored surgical interventions, including decompression and neurectomy.

Meaning: A structured, patient-specific algorithm that incorporates botulinum toxin response can optimize surgical planning and outcomes in occipital neuralgia.

INTRODUCTION

Occipital neuralgia (ON) is a debilitating craniofacial pain syndrome characterized by paroxysmal, shock-like pain in the distribution of the greater, lesser, or third occipital nerves.¹ Although modern diagnostic and therapeutic strategies have evolved significantly, the clinical entity was first described in 1821 by Spanish physicians José Benito Lentijo and Mateo Martínez Ramos.² Their observations—now referred to as Benito’s neuralgia—represent one of the earliest formal accounts of this complex pain syndrome. Overlap with migraine and cervicogenic headache complicates diagnosis, and International Classification of Headache Disorders (ICHD-3) criteria can be challenging to apply given heterogeneous presentations and anatomic entrapment patterns.³

Over the past 2 decades, an array of interventional and surgical treatments—including peripheral nerve blocks, botulinum toxin (BTX) injections, radiofrequency ablation, nerve decompression, neurectomy, ganglionectomy, and neuromodulation—have been applied with variable success.^4–6 However, the absence of a standardized diagnostic and therapeutic algorithm has led to inconsistencies in clinical practice, suboptimal patient selection, and a lack of consensus on treatment sequencing. Previous literature has largely focused on individual techniques or outcomes, with few efforts made to integrate these modalities into a unified, evidence-based decision framework.^7,8 Building on our prior meta-analysis, we aimed to synthesize the existing literature through a comprehensive systematic review and to present our clinical approach in the diagnosis and management of ON.⁹

METHODS

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. The review protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration number: CRD420251053204) (Fig. 1).

Fig. 1.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram. Study selection process for included reviews, illustrating records identified, screened, excluded, and retained according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines.

Eligible studies included systematic reviews, meta-analyses, narrative reviews, and clinical guidelines that addressed the evaluation and management of ON. Studies were included if they focused specifically on ON as defined by the ICHD-3, included adult populations, and described at least 1 therapeutic modality relevant to ON. Only English-language studies published between January 2000 and March 2025 were included. Case reports, small case series, editorials, and studies not focused specifically on ON were excluded.

A comprehensive literature search was conducted in PubMed, Embase, and Scopus with a search strategy including terms such as “occipital neuralgia” and “systematic review.” Two reviewers independently screened titles and abstracts using Rayyan systematic review software (A.T.N., M.F.E.). Full-text review was performed for studies meeting the inclusion criteria or requiring clarification. Disagreements were resolved through consensus with a third reviewer (R.D.G.). Data were extracted using a structured form capturing the following domains: author and year, study design, number and type of included studies, work-up, procedures described, key statistical findings, and recommendations.

Risk of bias was assessed using validated tools appropriate to the study design. For systematic reviews and meta-analyses, the AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) instrument was applied.¹⁰ Narrative reviews were evaluated using a modified Scale for the Assessment of Narrative Review Articles (SANRA) checklist.¹¹ Clinical guidelines were assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument.¹² (Table 1).

Table 1.

Risk of Bias Summary: Assessment of Included Reviews Using AMSTAR 2, SANRA, and AGREE II, With Domain Scores and Overall Quality Ratings

Data synthesis was narrative, with studies grouped by the primary intervention described (eg, decompression, neurectomy, BTX, or nerve blocks). Studies that presented clinical decision-making pathways were evaluated for alignment with our algorithm.

RESULTS

Fourteen review articles and clinical guidelines met the inclusion criteria and were analyzed in this systematic review.^{9, 13,14,16–25} (See table, Supplemental Digital Content 1, which displays an overview of the 12 included reviews and guidelines, detailing study type, treatment focus, and key contributions to ON diagnosis and management, https://links.lww.com/PRSGO/E705.) These included 7 systematic reviews or meta-analyses, 6 narrative reviews or case series with clinical decision frameworks, and 1 evidence-based consensus guideline. Publication years ranged from 2010 to 2025, with an increase in ON literature in the past 5 years. Study designs were heterogeneous, encompassing quantitative meta-analyses, qualitative treatment reviews, and interventional guidelines.

Work-ups typically included history, examination, and diagnostic blocks; some incorporated ultrasound/magnetic resonance neurography (MRN) or BTX response. Surgical and interventional approaches varied widely. Decompression of the greater and lesser occipital nerves was the most frequently studied procedure, with outcome improvement reported in 70%–96% of cases across several studies. Neurectomy and C2 ganglionectomy were generally reserved for refractory or revision cases. Neuromodulation—particularly occipital nerve stimulation (ONS)—was discussed in multiple guidelines and reviews as a last-line treatment for medically refractory cases, offering patient satisfaction despite limited high-level evidence. Two meta-analyses also examined acupuncture, which showed promise as an adjunct. Only a minority of studies provided structured treatment algorithms or decision aids. Among those that did, there was considerable variability in how diagnostic blocks, procedural selection, and escalation pathways were integrated into the treatment sequence.

ALIGNMENT WITH OUR CLINICAL APPROACH

Among the reviewed literature, the most comprehensive alignment with this framework was seen in Howard et al,²¹ who proposed a formal decision aid that stratifies patients by preference and nerve-sparing eligibility. Their model supports decompression as the preferred first-line surgical approach and incorporates neuromodulation for treatment-resistant cases. Similarly, Wamsley et al¹⁶ provided an intraoperative decision tree distinguishing between decompression and neurectomy based on anatomical findings and nerve quality, closely mirroring the surgical decision node in our model. Lee et al¹⁷ also adopted a block response–driven selection process for decompression under local anesthesia, reinforcing the role of preoperative diagnostics in patient stratification.

Earlier guidelines, such as Vanelderen et al²⁵ and Sweet et al,²⁴ presented linear treatment algorithms that included diagnostic blocks followed by corticosteroid injection, pulsed radiofrequency, and ultimately ONS.²⁰ Although these align with our broader treatment progression, they do not address surgical differentiation or incorporate BTX as a predictive tool. Similarly, Staudt et al²³ and Robinson et al²² provided broad intervention categorizations but lacked a structured flowchart or decision-making sequence.

Notably, no reviewed study fully integrates all components of our proposed framework—including BTX responsiveness, intraoperative fibrosis assessment, and a bifurcated failure pathway based on recurrence timing. As such, our approach represents a synthesis of current evidence and expert reasoning, aiming to unify disparate treatment paradigms into a comprehensive clinical workflow.

SPECTRUM OF ON

ON exists on a wide clinical spectrum that demands individualized consideration in both diagnostic testing and procedural planning.²⁶ At one end of the spectrum are patients with episodic neuralgia—short, severe jolts of pain that occur a few times per week. For these patients, nerve blocks performed during a symptomatic episode may offer both diagnostic clarity and therapeutic relief.²⁷ At the other end are patients with persistent, dull pressure or continuous throbbing pain, often accompanied by allodynia or radiation to the vertex.²⁸

Compounding this complexity is the fact that many patients referred for surgical evaluation have already undergone various interventions—oral medications, prior blocks—further complicating the diagnostic picture. As such, a one-size-fits-all algorithm is rarely sufficient.

APPROACH TO EVALUATION: DIAGNOSTIC AND THERAPEUTIC TOOL COMPARISON

The evaluation of patients with ON must account for its clinical heterogeneity and the nuanced roles of diagnostic interventions. Two of the most commonly used tools—BTX injections and occipital nerve blocks—contribute to the decision-making process.

BTX is often favored as an initial diagnostic and therapeutic modality due to its sustained duration of effect, typically providing relief during a 3- to 4-month period.²⁹ This extended window allows for clearer assessment of symptom reduction over time, particularly in patients with chronic or paroxysmal pain. However, BTX is not curative; its mechanism does not address bony or fascial-band compression, and its diagnostic specificity is limited.

Occipital nerve blocks, by contrast, serve as highly targeted, anatomy-driven tests that can provide immediate pain relief—often within minutes—for patients in acute distress. They are particularly useful for evaluating patients with discrete, episodic attacks or acute-on-chronic exacerbations.²⁷ Nevertheless, their short half-life (typically 24–72 h) limits their utility in chronic cases, and a negative result during asymptomatic periods may reflect poor timing rather than true diagnostic failure.

Rather than viewing these tools as interchangeable, we use them complementarily to guide timing, candidacy, and the likely success of surgery. In our experience, each test contributes distinct diagnostic and prognostic value.

OUR CLINICAL APPROACH FOR ON

Drawing upon findings from this systematic review and our previously published work on surgical outcomes in ON, we present our clinical approach to guide diagnosis and treatment selection (Fig. 2).

Fig. 2.

Proposed clinical algorithm for ON. Stepwise diagnostic and surgical management pathway, incorporating BTX, nerve blocks, imaging, and intraoperative decision-making between decompression and neurectomy. BoNT, botulinum neurotoxin; GON, greater occipital nerve; LON, lesser occipital nerve; TON, third occipital nerve.

Step 1: Predictive Stratification via BTX

BTX injection is the first-line confirmatory tool; the literature supports its use as a diagnostic tool with high positive predictive value.³⁰ All patients must meet ICHD-3 criteria for ON and undergo a thorough clinical examination to rule out overlapping headache disorders. Approximately 15 units of botulinum toxin A (BTX-A) is placed, though this may vary based on patient-specific factors. Our approach is similar to that described by Janis et al,³¹ who advocate for highly localized, trigger site–directed injections. The injection siteis based on pain with palpation or a positive Tinel sign. Classic injection points have been previously described. In our practice, injection patterns may be varied depending on patient-specific factors such as degree of focal tenderness, chronicity of pain, or history of block response, which helps ensure replicability across diverse presentations. For example, in patients with more diffuse trapezial involvement, we extend the grid to include trapezius trigger points, whereas in those with localized neuralgia, injections are concentrated along the greater and lesser occipital nerve trajectories. Greater than 50% symptom improvement sustained for 2–4 weeks suggests a compressive or entrapment-based etiology, favoring nerve-sparing decompression. Patients with transient or no response may instead harbor neuroma-in-continuity, dense fibrosis, or central pain amplification, supporting alternative strategies.

Step 2: Nerve Block

If the patient does not show improvement with chemo-deinnervation of the trapezius and paraspinous muscles, approximately 5 mL of 0.25% bupivacaine plain injection is placed along the course of the greater occipital nerves. Patients demonstrating 50% or more pain reduction for 24–72 hours are classified as likely peripheral neuralgia cases and considered for further intervention.^32,33 Those with absent or equivocal responses should be evaluated for central sensitization, cervicogenic sources, or other etiologies.

Step 3: Imaging and Anatomic Mapping

Ultrasound or MRN may be used to visualize nerve caliber, vascular compression, or perineural fibrosis. These findings guide surgical planning and procedural choice. We recognize that the utility of ultrasound and MRN may vary by institutional resources and radiological expertise. Although we incorporate these modalities selectively, particularly for complex or recurrent cases, we do not recommend their routine use unless guided by availability and clinical judgment.

Step 4: Procedural Decision-making

Patients are triaged into 1 of 2 primary surgical pathways:

• Occipital nerve decompression is selected for those with a favorable BTX response, imaging suggesting entrapment, posttraumatic etiology, or preserved nerve continuity on examination.³ Decompression may include fascial release, muscle debulking, removal of fibrous adhesions, and external neurolysis, depending on intraoperative findings. This approach is individualized to address patient-specific anatomical compression points.

• Neurectomy is favored in cases of poor BTX response, neuroma formation, dense fibrosis, or failure of prior decompression. Intraoperative assessment—such as flattened, fibrotic, or indurated nerves—may also prompt conversion from decompression to excision. Neurectomy is generally reserved for patients with persistent or recurrent symptoms following decompression, or in cases where intraoperative findings reveal neuroma-in-continuity or severe fibrosis. We acknowledge the risk of neuroma formation and use fascial flap coverage or relocation techniques to reduce recurrence.

Step 5: Postoperative Surveillance and Failure Management

If symptoms recur within 6 weeks, technical failure or incomplete decompression is suspected, warranting consideration of revision neurectomy. Recurrence after more than 6 months suggests possible central sensitization or newly evolved pathology. These patients are considered for escalation therapy, including:

• C2 ganglionectomy

• Peripheral nerve field stimulation

• ONS³⁴

• Spinal cord stimulation

These are reserved for medically refractory cases and ideally performed in specialized centers (Fig. 3).

Fig. 3.

Postneurectomy management algorithm. Treatment framework for patients with persistent or recurrent symptoms following neurectomy, including options for revision surgery and neuromodulation. GON, greater occipital nerve; LON, lesser occipital nerve; PNFS, peripheral nerve field stimulation; SCS, spinal cord stimulation.

CASE 1

A 37-year-old man presented with refractory ON characterized by persistent suboccipital pain. During a 5-month span, he underwent multiple ultrasound-guided C2 and third occipital nerve blocks by pain medicine specialists with temporary relief (20%–30% improvement lasting 2–3 wk). However, his symptoms persisted. During our first consultation, a diagnostic BTX injection was performed to differentiate between decompression and neurectomy. Based on his favorable response, we proceeded with bilateral greater occipital nerve exploration and decompression. Despite initial improvement, he returned 18 months later with recurrent right-sided pain. Examination suggested ongoing pinpoint neuralgia over his greater occipital nerve. A revision right greater occipital neurolysis and neurectomy were performed. Intraoperative findings revealed dense fibrosis and features consistent with ischemic neuropathy. Despite prior decompression, a neuroma-in-continuity was identified, likely due to ongoing fascial compression, inadequate release at the prior operation, or chronic microtrauma exacerbated by scar formation. This neuroma was excised, and a Z-plasty of the trapezius fascia was performed to reduce future compressive forces. This case illustrated the practical application of our approach, demonstrating how BTX response can guide initial surgical decision-making and how recurrence timing and intraoperative findings can prompt escalation from decompression to neurectomy.

CASE 2

A 43-year-old woman presented with a 3-year history of chronic posterior scalp pain (right > left), radiating to the forehead and temples. The pain was described as constant, sharp, and throbbing, and significantly interfered with sleep. Initial management included pharmacological therapy with gabapentin, amitriptyline, celecoxib, and hydrocodone–acetaminophen. The patient was referred to pain medicine, who performed monthly bilateral occipital nerve blocks for 8 months. Each injection yielded transient relief lasting 1–2 weeks. A consultation in our office included a BTX injection for surgical decision-making. However, she did not show any tangible improvement in her headache indices. Due to limited benefit from conservative management, the patient underwent bilateral surgical decompression and traction neurectomy of the greater and third occipital nerves. Intraoperative findings revealed inflamed and thickened nerve tissue bilaterally. Fascial release and neurolysis were performed at the trapezius and semispinalis levels, selected due to the inflamed, thickened appearance of the nerve bilaterally and refractory symptoms despite extensive prior medical and procedural treatments. Fascial release was performed to reduce the risk of neuroma. At the 8-month follow-up, the patient reported significant symptom improvement without evidence of recurrence. This case reinforced our framework by highlighting the role of limited block response in prompting decompression with neurectomy and how intraoperative findings can justify a combined approach.

DISCUSSION

The management of ON remains highly variable, often driven by individual provider preference and inconsistent access to interventions. Through this systematic review, we identified a broad range of treatment strategies for ON, yet few studies offered a cohesive framework to guide both diagnosis and intervention. Our goal was not to propose a rigid algorithm, but rather to describe a practical, mechanism-driven approach informed by both evidence and surgical experience.

A central paradigm in our clinical workflow is the prioritization of BTX-A as an initial diagnostic and therapeutic modality. Unlike nerve blocks, which provide transient relief and are highly dependent on timing, BTX offers a longer window of therapeutic response—typically 3–4 months—and can therefore provide insight into both symptom chronicity and response durability.³⁵ A favorable response to BTX suggests a compressive neuropathy, often amenable to decompression. By contrast, transient or absent responses may indicate more advanced pathology—such as neuroma-in-continuity or central sensitization—better suited to neurectomy or neuromodulatory options.³⁶ Although not traditionally used as a stratification tool, we found that BTX plays a crucial role in refining surgical candidacy.³⁷

Nerve blocks, although limited in duration, remain essential for patients presenting with acute pain or those in whom BTX is ineffective. Their value lies in anatomical precision and rapid feedback during active flares. However, a negative block performed during a quiescent period may yield a false-negative result, underscoring the need for clinical judgment in interpreting block efficacy. We use blocks selectively in patients with episodic neuralgia. Although our institutional practice incorporates BTX as a confirmatory tool in most cases, we acknowledge that prior studies, particularly by Guyuron et al,³⁸ have demonstrated the utility of nerve blocks alone in surgical decision-making. As such, our framework is adaptable and does not preclude proceeding to decompression based on diagnostic block response alone.

Importantly, surgical decision-making should remain flexible. Patients with strong BTX response and healthy intraoperative nerve appearance are good candidates for decompression. However, intraoperative findings of fibrosis, flattened or indurated nerves, or neuroma-in-continuity may prompt conversion to neurectomy.^39–41

Our approach also emphasizes postoperative surveillance and failure management. We distinguish early recurrence (<6 wk), typically reflecting technical failure or incomplete decompression, from late recurrence (>6 mo), which may indicate central sensitization or disease progression. These patterns inform escalation to revision surgery or neuromodulation, including C2 ganglionectomy, peripheral nerve field stimulation, or ONS.^42–44 Nerve capping, regenerative wrapping, and targeted muscle reinnervation have also been described in the literature for refractory cases or to prevent recurrence.^45–47 We have also encountered patients presenting for decompression or revision surgery after prior spinal cord or ONS. As such, step 5 reflects the practical need to assess these patients’ prior responses and ongoing candidacy for neuromodulation or C2 ganglionectomy within a multidisciplinary framework.

Limitations

Our review also highlighted persistent limitations in the ON literature. Most studies were retrospective, lacked control groups, or were limited by small sample sizes and heterogeneous outcome measures. Furthermore, although several systematic reviews supported decompression, ONS, or pulsed radiofrequency, the methodological quality of these reviews varied considerably. Only a minority used rigorous comparative analysis or proposed treatment sequencing. This heterogeneity reinforces the need for a cohesive framework to guide clinical decision-making.

Future Implications

Overall, our framework integrates diagnostic precision with adaptable, patient-specific pathways. It acknowledges the heterogeneity of ON and avoids a one-size-fits-all model. Although our algorithm is grounded in current literature and clinical experience, formal validation is needed. We plan to prospectively apply this framework in our practice and assess outcomes related to symptom resolution, surgical success, and recurrence patterns. Future multicenter collaboration may also support broader validation and refinement.

CONCLUSIONS

ON represents a complex and heterogeneous pain disorder requiring nuanced diagnostic evaluation and individualized treatment planning. Although prior literature has focused on isolated interventions, few have integrated diagnostic tools and failure management into a cohesive framework. Our systematic review highlighted this gap and supported the development of a flexible, mechanism-based clinical approach. Future prospective studies are needed to validate this approach and refine patient selection criteria across surgical and neuromodulatory strategies.

DISCLOSURE

The authors have no financial interest to declare in relation to the content of this article.