This retrospective study collected clinical data from patients diagnosed with chronic cluster headache who underwent upper cervical spinal nerve root release surgery at the Pain Department of Chuanbei Medical College Affiliated Hospital, spanning from August 2020 to March 2023. Eligibility for participation was determined based on several inclusion and exclusion criteria.

Upon admission, each patient underwent a thorough diagnostic assessment that included computed tomography (CT) and magnetic resonance imaging (MRI) of the head and cervical spine. These imaging procedures are essential for accurately identifying any lesions within the central nervous system that could impact the surgical approach or outcome. Additionally, routine preoperative evaluations were conducted to ensure there were no contraindications to surgery. This preparatory phase is designed to optimize patient safety and surgical efficacy by addressing potential risks and complications before proceeding with surgery.

Preoperative pain assessment was carried out as follows using a custom-designed 10 cm (100 mm) visual analog scale (VAS) ruler, featuring standardized anchors at both extremities: “No pain” (0 points) at the left terminus and “Maximum imaginable pain” (10 points) at the right terminus. Assessments were conducted in a controlled environment ensuring patient comfort and communicative readiness. Prior to evaluation, patients received standardized instructions regarding VAS interpretation and marking procedures. Participants were instructed to place a perpendicular mark along the linear scale reflecting their subjective pain intensity. Scoring methodology was carried out as follows. The distance between the “No pain” anchor and the patient’s mark was measured in centimeters, with proportional conversion to a 0–10 numerical scale. For instance, a mark 3 cm from the pain-free end corresponds to a VAS score of 3. Continuous validation was maintained through endpoint confirmation—unmarked endpoints received default scores (0 or 10) while intermediate positions were calculated through metric interpolation.

Patients were required to fast for 6 h prior to the surgery. The entire operation was conducted by a chief physician with over 30 years of experience in interventional procedures. The Philips 64-row spiral CT served as the guiding device throughout the procedure.

The frequency of headache episodes (weekly occurrences), the average duration of each episode, the pain intensity (using the Visual Analog Scale [VAS], ranging from 0 to 10) (17), and any accompanying symptoms (such as conjunctival congestion, tearing, nasal congestion, runny nose, etc.) should be tracked and documented before and after the surgery.

The patients’ quality of life should be assessed before and after surgery using the Headache Impact Test (HIT) and additional questionnaires (18). The HIT includes various questions that measure the impact of headaches on daily activities, work, study, and emotional well-being. Higher scores indicate a greater negative impact on quality of life.

Any complications occurring during and after the surgery, such as bleeding, infection, nerve damage (e.g., upper limb numbness or weakness), cerebrospinal fluid leakage, and other potential issues should be monitored and recorded.

The study enrolled 17 patients diagnosed with chronic cluster headache who underwent upper cervical spinal nerve root release surgery. The cohort consisted of 12 men and 5 women, ranging in age from 25 to 58 years, with a mean age of 41.5 ± 8.2 years. The duration of their condition spanned 2 to 28 years, averaging 11.7 ± 4.4 years. Prior to the surgery, the frequency of headache episodes varied from 1 to 9 times per week, with an average of 5.4 ± 2.1 episodes. The duration of these episodes ranged from 10 to 120 min, with an average duration of 35.3 ± 21.5 min. The intensity of the headaches, as measured by the Visual Analog Scale (VAS), ranged from 4 to 9, with an average score of 7.29 ± 1.48 (Table 1).

Six months post-surgery, significant improvements were observed in the management of chronic cluster headache among patients. The average Visual Analog Scale (VAS) score markedly reduced from 7.29 to 1.75. Similarly, the frequency of headache episodes decreased from an average of 5.4 times per week to just 0.76 times. Additionally, the average duration of each episode was reduced from 35.32 min to 4.55 min.

Statistically significant reductions in VAS scores were noted at all follow-up time points (p < 0.05): 1 week post-surgery (2.76 ± 1.16), 1 month (2.25 ± 0.45), 3 months (1.95 ± 0.47), and 6 months (1.75 ± 0.48), as shown in Figure 2. Similarly, the frequency of headache attacks progressively decreased over the 6-month period: 1 week post-surgery (1.96 ± 0.42 times), 1 month (1.45 ± 0.36 times), 3 months (0.95 ± 0.32 times), and 6 months (0.76 ± 0.28 times), detailed in Figure 3. The duration of each headache episode also showed a consistent decrease: 1 week post-surgery (14.68 ± 4.75 min), 1 month (9.44 ± 3.28 min), 3 months (6.65 ± 2.52 min), and 6 months (4.55 ± 1.34 min), as illustrated in Figure 4.

Within 24 h post-surgery, 15 patients experienced significant relief from headaches, while 2 reported unsatisfactory outcomes. Following this, contralateral C3/4 segment surgery was performed 2 days later. Post-operatively, one patient suffered transient vomiting and another experienced numbness in the upper limb; The vomiting patients were relieved quickly after symptomatic treatment with intravenous injection of ondansetron; The numbness in the upper limbs was relieved 1 week after symptomatic treatment.

The Headache Impact Test (HIT) was used to assess changes in quality of life. Initially, the average preoperative HIT score was 71.05. Subsequent measurements showed a decrease to 48.06 ± 6.37 1 week after surgery, 44.50 ± 3.46 after 1 month, 41.90 ± 2.62 after 3 months, and 39.43 ± 1.34 after 6 months. These results indicate a substantial and progressive improvement in quality of life, as depicted in Figure 5.

This study enrolled 17 patients with cluster headache who underwent upper cervical spinal nerve root release surgery. Over a 6-month follow-up period, significant relief in headache symptoms was observed, with notable reductions in frequency, duration, and intensity of pain. Additionally, there was a marked improvement in the patients’ quality of life. By the 6-month follow-up, the symptoms for most patients were essentially under stable control, indicating that upper cervical spinal nerve root release surgery is an effective treatment for cluster headache. Although the sample size is small, the use of repeated measures ANOVA enhances statistical power by analyzing within-subject changes over time. The large effect size observed, coupled with a highly significant p-value, suggests that the improvements are clinically meaningful and not merely a statistical artifact.

However, two patients initially did not experience significant pain relief and subsequently underwent contralateral spinal nerve root release, which resulted in considerable improvement. This seemingly paradoxical outcome may be explained by the profound neurophysiological changes that occur in severe, chronic pain states, particularly the key mechanism of central sensitization. In this study, patients with long-standing, refractory cluster headache, the persistent and intense unilateral nociceptive barrage can lead to a state of hyperexcitability within the central nervous system, most notably the trigeminocervical complex (TCC), which serves as the integration center for head and neck pain (21–23). Neuroanatomical and electrophysiological studies provide a solid foundation for this phenomenon. Firstly, the TCC is not a functionally segregated structure but rather a functional continuum where its neurons receive convergent inputs from both the trigeminal and upper cervical spinal nerves (21). Crucially, these neurons receive inputs not only from the ipsilateral side but also from the contralateral side. The existence of transmedian fibers that cross the midline provides a direct anatomical pathway for this bilateral “crosstalk” (24). Under normal physiological conditions, afferent input from the contralateral side is typically sub-threshold and does not elicit a pain response. In a state of central sensitization, however, this changes fundamentally. Evidence from animal models shows that a unilateral inflammatory or nerve injury significantly increases the number of spinal neurons with bilateral receptive fields and can even switch their response from inhibitory to excitatory (25). Therefore, we hypothesize that for these two exceptionally refractory patients, their condition had evolved from a localized unilateral issue to a centralized disorder. The initial ipsilateral surgery addressed the primary driver of pain, but the nervous system remained too sensitized to return to a non-painful state. In this hyperexcitable condition, even minor, previously subclinical irritation on the contralateral side—such as the subtle nerve root irritation we noted upon imaging review—was sufficient to perpetuate the hyperexcitability of the TCC and maintain the pain cycle. The subsequent contralateral procedure was likely effective because it eliminated this secondary, yet critical, nociceptive input, finally breaking the pathological cycle and allowing the sensitized central nervous system to quiet down.

Upper cervical spinal nerve root release surgery may offer relief through several mechanisms. First, there is neurological function regulation. The surgery potentially influences nerve signal transmission in headache-related structures, such as the trigeminal spinal tract nucleus and the hypothalamus, thus modulating neurological functions and diminishing headache symptoms (26, 27). Studies indicate that cluster headaches involve abnormal activation of the trigeminal neurovascular system, which results in vasodilation and neurogenic inflammation. The trigeminal cervical complex, a pivotal anatomical and functional entity in the pathogenesis and management of refractory headaches, simultaneously receives afferent fibers from the trigeminal nerve and superior cervical spinal nerve (C1-C2) and promotes the transmission and regulation of pain signals (8–11). Surgical decompression of the nerve roots in the upper cervical spine may thus reduce trigeminal nerve excitability and alleviate pain. Second, you can enhance local blood circulation. The surgical intervention may enhance blood flow around the cervical nerves, decrease the release of inflammatory mediators, and thus mitigate headache symptoms. Research by Bakhtadze et al. proposes that spinal joint dysfunction can lead to cerebral hypoperfusion via overactivity of the regional sympathetic nervous system, potentially elucidating the pathogenesis of certain intractable headaches (28). In this study, the surgical release of spinal nerve roots can effectively relax local sympathetic nervous tension, boost blood circulation, and consequently aid in reducing neuroinflammation and pain.

The potential pharmacological mechanisms of transforaminal upper cervical epidural ozone injection in this surgical procedure include the following. First, there is the neuromodulatory effect, where the oxygen-ozone mixture, characterized by strong oxidative properties and excellent tissue diffusibility, induces mechanical separation of perineural adhesions (29). Second, there is nociceptive modulation, where ozone selectively inhibits the release of nociceptive neurotransmitters, particularly reducing concentrations of substance P and calcitonin gene-related peptide (CGRP), thereby attenuating peripheral sensitization processes (30). Third, there is the anti-inflammatory cascade, where ozone exerts dual anti-inflammatory actions through suppressing synthesis of proteolytic enzymes and pro-inflammatory cytokines (e.g., TNF-α, IL-6), while activating the Nrf2 pathway to enhance antioxidant enzyme expression. This combined effect effectively neutralizes oxygen free radicals and preserves neural structural integrity, ameliorating neurogenic inflammation during cluster headache episodes (31, 32). Fourth is neuronal regulation, where ozone activates inhibitory interneurons in the spinal dorsal horn, promotes the release of endogenous analgesics (e.g., enkephalins), and modulates neuronal excitability through sodium-potassium channel regulation, collectively modifying pain transmission pathways (33).

In terms of safety, only minor complications were reported. One patient experienced transient vomiting, and another reported temporary upper limb numbness post-surgery; both conditions resolved within a week with symptomatic treatment. No other significant complications were noted, underscoring the high safety profile of the surgery.

Conduct multi-center, large sample studies to more accurately evaluate the efficacy and safety of surgery.

Further observe the long-term effects and recurrence of surgery, as well as the long-term impact on the patient’s quality of life.

We recognize the importance of further verifying the efficacy of upper cervical nerve root release surgery. One potential approach may be to conduct multiple-center, randomized controlled trials with a placebo group to better understand the mechanism of action of the surgery and further support its efficacy.