FormalPara Key Summary Points

Why carry out this study?

GLOA (ganglionic local opioid analgesia) at the SCG (superior cervical ganglion) is performed for pain control and is known to be a safe and effective procedure with low complication rates

This procedure has, however, very variable effects on post-interventional pain scores, possibly due to different patterns of fluid spread in anatomic regions leading to these inconsistent post-interventional pain outcomes

The primary objective of the present study was to evaluate the spread of the injected substance in the area of the SCG immediately after GLOA

We also expected a correlation between the area and volume of the injectate spread and documented post-procedural pain scores and other clinical outcome measures

What was learned from the study?

To the best of our knowledge, this is the first published magnetic resonance imaging analysis focused on fluid spread in the area of the SCG immediately after GLOA

Clinicians should be aware of a laterodorsal needle direction to prevent possible block failures

A total volume of 2 ml injected into the parapharyngeal space and its “medial compartment” is recommended to reach the SCG. Higher volumes may lead to uncontrolled distribution patterns. especially when the stylopharyngeal fascia is absent

Introduction

The injection of low-dose opioids (mainly buprenorphine or sufentanil) to different sympathetic ganglia has been termed “ganglionic local opioid analgesia” (GLOA) [1, 2]. This form of therapy has been successfully used for numerous, often protracted diseases that severely impair the patient’s quality of life, such as idiopathic facial pain syndromes, trigeminal neuralgia or postherpetic neuralgia [3].

The superior cervical ganglion (SCG) is the largest of the cervical ganglia and the uppermost cranial part of the sympathetic chain (see Fig. 1). Due to the fusion of four segmental ganglia, it is 3–5 cm in length, fusiform in shape and often flattened. Located anterior to the longus capitis muscle and the transverse process of the second and third (and sometimes fourth) cervical vertebrae, and dorsal to the internal carotid artery (ICA), it provides sympathetic innervation to the face and head with branches to the jugular nerves, the internal carotid artery, the second and third cervical somatic nerves and the superior cervical cardiac nerve [2, 4].

Fig. 1
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Magnetic resonance image of the superior cervical ganglion (red asterisks)

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The SCG is situated next to the pharynx, in the parapharyngeal or lateropharyngeal space. The parapharyngeal space represents the most cranial extension of the so-called prevertebral interfascial space, also known as the “Danger space” of Grodinsky and Holyoke [5], located dorsolateral to the pharynx. This space continues to the contralateral side ventrally to the prevertebral fascia. The prevertebral space, which is found dorsal to the prevertebral fascia, contains the prevertebral muscles and continues laterodorsally into the neck and to the intervertebral foramen, which is a direct continuation of the epidural space. The ventral border of the parapharyngeal space is the intercarotid fascia at level of the C4 cervical vertebra and more cranially its fusion with the buccopharyngeal fascia [6, 7]. Laterally to these fascia and the pharyngeal wall is the stylopharyngeal fascia, developed between the outermost corner of the pharynx and the styloid process. Therefore, in case of the existence of latter fascia, the parapharyngeal space has no direct connection with the ventromedially located infratemporal fossa and the ventrolaterally located retromandibular fossa. The parapharyngeal space contains the ICA. Medial and dorsal to the ICA is the superior cervical ganglion. In addition, there are the hypoglossal, glossopharyngeal, vagus and accessory nerves as well as the most laterally located internal jugular vein. Regarding the topography of the parapharyngeal space, this space is easily reachable via the pharyngeal recessus of Rosenmüller, which is dorsal to the palatopharyngeal arch [8,9,10].

Although the exact mechanisms of action for GLOA at the SCG has yet to be elucidated, it has been stated that modulation of ganglionic transmission with opioids may reduce efferent impulses through postganglionic sympathetic fibers or inhibit activation of nociceptors in sympathetically mediated pain [11].

GLOA at the SCG is performed for pain control and is known to be a safe and effective procedure with low complication rates [1, 3, 8, 12, 13]. Minor complications are mostly considered to be due to the accidental intravasal injection of opioids, leading to sedation, nausea and vomiting. Also, respiratory depression or collapses have been reported, in addition to pain at the injection site, vertigo, dysphagia and transient hoarseness [1].

The primary objective of the present study was to evaluate the spread of the injected substance in the area of the SCG immediately after GLOA. We expected to find a correlation between the area and volume of the injectate spread and documented post-procedural pain scores and other clinical outcome measures.

Methods

Ethical Approval

This case series was approved by the Ethics Committee of Carinthia (S2021-34) and registered on clinicaltrials.gov (clinicaltrials.gov identifier NCT05257655; date of registration 2022-02-25; patient enrollment date from 2023-01-09 to 2023-08-31). Informed consent was obtained from every participant. Participants were identified only by a number, rather than by a name or initials. The study was conducted according to the Declaration of Helsinki and the International Association for the Study of Pain (IASP) guidelines for pain research in animals and humans, and authorized by the hospital’s general management.

Setting

This study was conducted at the outpatient pain center of the general hospital Klagenfurt am Wörthersee. All cases treated in this department presenting from January 2023 to May 2023 were screened for eligibility. Inclusion criteria were adult patients (≥ 18 years of age) with a planned GLOA at the SCG for the treatment of trigeminal neuralgia, trigeminal post-herpetic or post-zoster neuralgia, or neuropathic pain syndromes in the head area (e.g. atypical facial pain, glossopharyngeal neuralgia). The exclusion criteria were psychosis, a language barrier, pregnancy or breastfeeding, seizure disorders (epilepsy) and an increased risk of bleeding. The hospital charts of these patients were reviewed to extract demographic data and baseline clinical characteristics. All GLOA series were embedded in a multimodal interdisciplinary therapy concept as described in the actual guidelines [14].

Procedure

The technique of GLOA used at the SCG was as follows. Using a standardized protocol and technique, all GLOA at the SCG were performed by two physicians (S.N.-S., R.L.), who are experts in this field. No premedication or sedation was given before the intervention. Each intervention was performed under standard monitoring with intravenous access established. Patients were positioned in a sitting position close to the magnetic resonance imaging (MRI) scanner and a transoral blocking technique [15] was used to achieve the SCG.

Under direct visual control, a Sprott-canula (Sprotte® 25G × 90 mm; PAJUNK, Geisingen, Germany) was inserted transoral into the pharyngeal recessus of Rosenmüller located dorsal to the palatopharyngeal arch and pierced through the pharyngeal wall into the parapharyngeal space at the height of the second cervical vertebra (C2) or intersection at the first and second cervical vertebrae (C1/C2) level. By using a “stopper” or “spacer” (SCG spacer; PAJUNK), the infiltration of this Sprotte-canula can be assured at a maximum of 1 cm, to avoid accidental carotid artery puncture (see Fig. 2).

Fig. 2
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Drawing of a transoral performed GLOA. The Sprotte distance-holder is advanced from the contralateral side in the pharyngeal recess. The needle is then advanced into the parapharyngeal space with neurovascular structures. GLOA Ganglionic local opioid analgesia, ICA internal carotid artery, IJV internal jugular vein, PR pharyngeal recess, PVF prevertebral fascia, SCG superior cervical ganglion, SPF stylopharyngeal fascia, SPM stylopharyngeal muscle, T tongue, VN vagus nerve (representing all other cranial nerves such as IX, XI and XII)

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When the needle tip was in the targeted position, suction was applied to detect an unexpected intravasal position. After confirmation that the needle tip was in the appropriate position, 5 μg of Sufentanil (Sufentanil; Hameln Pharma, Hamelin, Germany) mixed in 2 ml of sodium chloride was injected. The time of the block was registered.

Following the injection, neck MR imaging was carried out with patients lying in a supine position. All MRI examinations were performed using the same 3-Tesla-scanner (model “Ingenia”; Philips, Amsterdam, The Netherlands). In total, five sequences were performed. The T1-weighted axial sequence was acquired by covering the skull base to the level of the first thoracic vertebra (Th1). T2-weighted axial images with a slice thickness of 4 mm, STIR fat-suppressed T2-weighted coronary sequences and SPAIR fat-suppressed sagittal images were acquired. The T2-weighted sequences were primarily used for anatomical orientation and to show possible anatomical alterations. Additionally, a heavily T2-weighted isotropic (T2 3D Drive) sequence was performed at the level of the injected area. The spread of the injected solution was evaluated using the T2-weighted sequences. If the contrast of the solution was clear, the spread was recorded as positive [16].

Evaluation

The blinded MRI scans were reviewed retrospectively by an anaesthetist and pain specialist (S.N-S.), an anatomist (G.F.) and a radiologist (S.I.) separately and interpreted descriptively. The spread of the injected solution was evaluated based on the visible presence of the contrast of the solution on the MRI scans (see Figs. 3, 4).

Fig. 3
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Magnetic resonance imaging scan showing solution spread (asterisk) in the parapharyngeal space and its “medial compartment”

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Fig. 4
figure 4

Magnetic resonance imaging scan showing solution spread in the craniocaudal direction (asterisk)

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Assessors evaluated the anatomical area of the fluid spread, the furthermost spread of the injectate from the midline to a craniocaudal, sagittal, lateral and contralateral (if applicable) direction (in millimeters), any hampered spread of the injectate due to regional anatomical alterations and a swelling of the pharyngeal wall after the intervention. In addition, the contact of the injected solution with other structures and the carotid artery was evaluated. Based on this information, the assessors estimated side effects and the efficacy of GLOA on pain release.

Secondary Outcome Measures

Pain Assessment

Before and after every GLOA and after 1 and 3 months, the present pain intensity was rated on a 0–10 Numerical Rating Scale (NRS), with 0 corresponding to “no pain” and 10 to “the worst pain imaginable.”

Quality of Life Questionnaire

Before the first and after the fifth GLOA and after 1 and 3 months, each patient was asked to complete a quality of life questionnaire (European Quality of Life 5 Dimensions 5 Level Version [EQ-5L-5D]). This descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has five levels: no problems, slight problems, moderate problems, severe problems and extreme problems. Each patient was asked to indicate their health state by ticking the box next to the most appropriate statement in each of the five dimensions, thereby generating a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patients’ health state [17].

Patient Satisfaction

Before the first and after the fifth GLOA and after 1 and 3 months, the patients were asked to complete the Fragebogen zur Messung der Patientenzufriedenheit (ZUF-8) questionnaire, an instrument used to measure the global, one-dimensional recording of patient satisfaction. This questionnaire is the German-language adaptation of the American Client Satisfaction Questionnaire (CSQ-8). General satisfaction with aspects of the clinic or the treatment received was recorded using eight items. ZUF-8 is particularly suitable for an economical screening of patient satisfaction [18].

Sleep Quality

Before the first and after the fifth GLOA and after 1 and 3 months, the patients were asked to complete a questionnaire on sleep quality (Pittsburgh Sleep Quality Index [PSQI]) [19].

Efficacy Prediction Based on MRI-Verified Fluid Spread

Efficacy prediction (post-procedural NRS) was based on the MRI-verified fluid spread in millimeters and the calculated volume of solution spread in the area of the superior cervical ganglion.

Statistical Analysis

Descriptive statistics were used for all measured variables. Appropriate parametric or non-parametric tests were used. Tables were analyzed using the Fisher-Yates test (exact Fisher test) and the Chi-square test. Regressions were determined by the least square method. To evaluate confidence intervals (CI), exact limits were determined. Comparisons of ordered data were performed using the Wilcoxon-Mann–Whitney U-test. Deviations from zero were investigated using the signed rank test. Correlations and significance are described by the Spearman’s rank correlation coefficient ρ. Significance was defined as a p-value < 0.05; p-values are reported to a maximum of three decimal places. Statistical evaluations were performed in R (version 4.0.3, 2020; https://www.r-project.org or, for elementary statistics and figures, in HP-RPL (version 2.08, 2006; Hewlett-Packard Company, San Diego, CA, USA).

Results

Diagnoses, demographic data, baseline patient characteristics, pain-related data, complications and the main results of the spread of neurolytic solution are shown in Table 1. The different correlations are shown in Table 2.

Table 1 Main results
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Table 2 Correlations
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Demographic Data

In summary, 15 procedures were performed on two women and one man. Each patient received five MRI-controlled GLOA procedures at the SCG.

Spread of the Injected Solution

Based on imaging of the cervical spine, the main solution spread reached from the C1 to C3 (53.3%), followed by C2 to C4 (13.3%) and base of the skull to C2 (13.3%). In 6.7% of cases, the spread was from C1 to C2, C2 to C3 and C1 to C4.

Measured from the midline, the furthest solution spread to the lateral was 21.2 mm, while it was 15.2 mm to the sagittal. When a contralateral solution spread occurred (60% of cases), the furthest spread was 12.6 mm. The furthest craniocaudal solution spread was 63.5 mm. In two cases (13.3%), the solution spread was 10.7 mm and 3.8 mm distant from midline.

Spread of the Injected Solution in Anatomical Spaces

In 53.3% of cases, the solution was found in the parapharyngeal space with an additional spread to the midline or even contralateral side; in 33.3% of cases, the injectate was detectable in the “medial compartment” of the parapharyngeal space, which corresponds to the space dorsal to the pharynx; in 6.6% of cases, it was detectable in the parapharyngeal space; and in 6.6% of cases, it was detectable in the prevertebral space.

Statistical analysis showed a significant (p = 0.025) correlation of solution spread in the parapharyngeal space and its “medial compartment” and pain relief compared to solution spread in the prevertebral space or “medial compartment” only. Also, a highly significant (p = 0.0088) correlation of volume of solution spread and solution spread in the parapharyngeal space and “medial compartment” was found.

Volume of Solution Spread

The volume of solution spread was calculated (in millimeters) using three separate measures (lateral/contralateral, craniocaudal, sagittal). The real volume of solution spread is cloud-shaped; in the calculation, an ellipsoid-shaped volume spread was assumed. We found a highly significant (p = 0.0014) correlation between the volume of solution spread and change in NRS (see Fig. 5).

Fig. 5
figure 5

Correlation between volume of solution spread and change in NRS. NRS Numerical Rating Scale

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Spread of the Solution in “Unexpected” Areas

In one intervention, the solution was partially found in the pharyngeal wall.

Spread of the Solution in the Area of SCG

In all cases, the SCG was detected on MRI scans. In 14 of the 15 interventions (93.4%), the fluid showed a complete spread in the area of the SCG. In one intervention (6.6%), the fluid did not affect the SCG.

Contact Between Solution and Carotid Artery

In two procedures (13.3%), the solution made contact with the dorsal part of the carotid artery.

Regional Anatomical Distortions

No hampered spread of the solution was observed due to anatomical distortions.

Swelling of the Pharyngeal Wall after Intervention

In ten interventions (66.6%), a swelling of the pharyngeal wall at the injection site was observed. No statistically significant correlation of swelling and post-procedural pain scores (p = 0.41) and volume of solution spread (p = 0.37) was found.

Stylopharyngeal Fascia

The stylopharyngeal fascia was observed in 100% of cases.

Pain Intensity

Before the first GLOA, the mean ± standard deviation [SD]) pain intensity (11-item NRS; 0 = “no pain” to 10 = “worst pain imaginable”) was 2.00 ± 2.00, with a 1.33-point pain reduction after the first GLOA. Before the second GLOA, the mean pain intensity was 1.00 (± 1.00), with a 0.33-point pain reduction after the second GLOA. Before the third GLOA, the mean pain intensity was 1.67 (± 2.08), with a 1.00-point pain reduction after the third GLOA. Before the fourth GLOA, the mean pain intensity was 0.33 (± 0.58), with a − 0.67-point pain reduction after the fourth GLOA. Before the fifth GLOA, the mean pain intensity was 1.00 (± 1.73) with a − 0.67-point pain reduction after the fifth GLOA.

We found a negative correlation between pain reduction and number of GLOA (p = 0.027). There was evidence that higher pre-procedural pain intensity is correlated with higher pain reduction after GLOA (see Fig. 6). Compared to the second follow-up, a statistically significant (p = 0.22) but clinically irrelevant (0.33 points) pain increase was shown.

Fig. 6
figure 6

Higher pre-procedural pain intensity was found to be correlated with higher pain reduction after GLOA at the SCG. GLOA Ganglionic local opioid analgesia, SCG: superior cervical ganglion

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Predictive Value of Spread of the Injectate for Post-procedural Pain Relief

Based on the spread of the solution and the anatomical structures and spaces that were reached, we expected a correlation between the area with solution and documented post-procedural pain scores.

Pain relief was estimated incorrectly in only one procedure. In five observations, we estimated the post-procedural pain relief correctly, and there was no change in post-procedural pain scores in nine observations. Therefore, in 83% (95% CI 35.9–99.6) of cases, we estimated correctly the expected post-procedural pain scores due to the correct spread of the injectate; in addition, when “no negative change in post-procedural pain scores” was also rated as a success of GLOA, we estimated the pain relief in 93% (95% CI 68.1–99.8) of procedures correctly.

Lateral versus Sagittal Blockade Technique

The needle was advanced in the laterodorsal direction in four interventions, while a more mediodorsal direction was preferred in 11 interventions.

We found no correlation (p = 0.33) between post-procedural NRS scores and the different approaches. The correlation of a higher volume of solution spread with a strict lateral approach fell just short of being statistically significant (p = 0.11) (see Fig. 7).

Fig. 7
figure 7

Boxplot of different approaches versus volume index, showing a trend for higher volume of solution spread with lateral approach (p = 0.11). Int_1 More sagittal approach (n = 11), Int_2 the lateral approach (n = 4).

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PSQI, EQ-5L-5D, ZUF8

The mean (± SD) PSQI score was 4.9 ± 2.5, mean EQ-5L-5D score was 73.6 ± 17.2 and mean ZUF8 score was 31.5 ± 1.25. A statistically significant (p = 0.086) correlation of patient satisfaction and lower post-procedural NRS scores was found. Also, a statistical trend (p = 0.11) to higher patient satisfaction and volume of solution spread was found. A correlation of quality of life and sleep quality fell just short of statistical significance (p = 0.28). A statistically significant (p = 0.027) but clinically irrelevant decrease in sleep quality was found. No other statistically significant results or trends in correlation with PSQI, EQ-5L-5D and ZUF8 were found.

Complications

No minor or major complications occurred in patients who underwent this procedure. There was no correlation between contact of the solution with the carotid artery and complications.

Discussion

Previous studies have shown that GLOA is a safe and effective procedure [1, 3, 8, 12, 13], but that it also has very variable effects on post-interventional pain score. A retrospective evaluation by Elsner et al. [8] showed that GLOA could initially lead to a 99% reduction in pain but that an increase in pain scores is also possible. These authors reported a pain reduction in 66% of patients in the medium term (up to 7 days), with 21% of patients reporting a decrease of pain outcomes in the long term (a mean of 3 years). Spacek et al. [12] performed an uncontrolled retrospective analysis of 21 patients and reported a beneficial effect of GLOA on the SCG in patients with trigeminal neuralgia. In a different analysis, this same group showed that GLOA on SCG failed in 37% of interventions [13]. Feigl et al. [9] showed that the stylopharyngeal fascia, which can be found in 84% of cases, could lead to a hampered spread of the solution, with the consequence of a decreased effect on the third or even second branch of the trigeminal nerve.

Elsner et al. stated [3] that different patterns of fluid spread in anatomic regions may lead to these inconsistent post-interventional pain outcomes after GLOA on the SCG. In a cadaver study, Feigl et al. [3] evaluated the distribution patterns after GLOA at the SCG according to different volumes injected. In 30 patients, these authors injected 1 ml of contrast (Jopamiro®; Bracco, Milan, Italy) on the left side (group 1) or 2 ml of contrast medium on the right side (group 2); in ten patients (group 3) they injected 5 ml of contrast on the left side in a more sagittal direction, and 5 ml of contrast on the right site in a more lateral direction, as described by Pejic et al. [15]. Computed tomography (CT) scans were taken directly after the intervention, and the spread of contrast medium was evaluated. In the first group, receiving fluid from a needle in a more lateral direction,, the contrast medium was found in the parapharyngeal space in 67% of interventions. In most of these cases, the contrast medium spread from the base of the skull to C2 and reached the dorsal side of the ICA. In 27% of cases, the contrast medium reached the prevertebral space with spreading from the base of the skull to C3. Higher resistance was noted during the application in the prevertebral space. In the second group, 2 ml of contrast was injected in the parapharyngeal space. In 95% of cases, the contrast spread from C2 to C3, frequently reaching further to the dorsal side of the ICA but never reaching the intervertebral foramen. In 6% of cases, the contrast medium was injected in the prevertebral space with a maximum spread up to the C2. In this group also, a higher resistance was noted during the application. In the third group, 5 ml of contrast was injected into the parapharyngeal space. The fluid was observed to spread from the base of the skull to C4 and also reached the infratemporal fossa and the retromandibular fossa. In addition, the contrast medium was found in the transverse and intervertebral foramen. When 5 ml of contrast was injected in the prevertebral space, the fluid was found in the transverse and intervertebral foramen and also reached different muscles of the neck and spread until the C4. When the stylopharyngeal fascia was present, the contrast medium reached various anatomical structures, including the SCG, ICA, internal jugular vein, glossopharyngeal, accessory, vagus and hypoglossal nerves when injected in the parapharyngeal space. When the stylopharyngeal fascia was absent, 2 ml of contrast medium reached the infratemporal fossa. When the liquid was injected into the prevertebral space behind the prevertebral fascia, which acts like a barrier, the parapharyngeal space with the SCG was not reached [3].

Artefactual changes in locations due to postmortem changes may lead to different findings in cadaveric studies compared to in vivo evaluations. Hence, MRI can be applied to evaluate these postmortem findings in living participants.

To the best of our knowledge, our study is the first published report of an MR imaging analysis focused on fluid spread in the area of the SCG immediately after GLOA. On the basis of recent anatomic studies [16], MRI allowed the detection of SCG, with the longus capitis muscle and ICA as landmarks. In our patients, SCG was found at the level of the C2-C4 vertebrae, with a fusiform-elongated shape. Also, different anatomical spaces, in terms of the parapharyngeal space and its “medial compartment,” and prevertebral space, were clearly identified on MRI. The injected fluid was visible in the T1-weighted sequences, as expected.

In this study, we injected 2 ml of fluid transoral into the pharyngeal recessus of Rosenmüller located dorsal to the palatopharyngeal arch. In more than 50% of interventions, the main solution spread reached from C1 to C3, with the furthest craniocaudal solution spread being 63.5 mm. The solution was mostly found in the parapharyngeal space and its “medial compartment,” followed by the “medial compartment” alone. In 93.4% of interventions, the fluid was observed to have spread out completely in the area of the SCG, while in 6.6% of interventions, the solution was found in the prevertebral space and hence did not affect the SCG. In only 13% of cases did the solution come into contact with the dorsal part of the ICA, and no hampered spread due to anatomic distortions was found.

In the cadaveric studies of Feigl et al. [3, 9], 2 ml of contrast medium injected in the parapharyngeal space spread from C2 to C3 and reached the dorsal side of the ICA. Also, in 6% of cases, the solution was found in the prevertebral space. Although these studies described a higher resistance when injecting the fluid in the prevertebral space, we cannot confirm this finding.

We found a significant correlation of solution spread in the parapharyngeal space and its “medial compartment” and pain relief compared to solution spread in the prevertebral spread or the “medial compartment” alone. As described above, the prevertebral fascia is a solid barrier between the prevertebral space and parapharyngeal space, and hence the SCG could not be reached by the solution [3].

The furthest solution spread to the lateral was 21.2 mm, while it was 15.2 mm to the sagittal. In combination with the craniocaudal solution spread, we assumed a cloud-shaped solution spread. To demonstrate an association between distribution patterns and secondary outcomes, we assumed an ellipsoid-shaped volume spread. Interestingly, we found a highly significant correlation of the calculated volume and the solution spread in the parapharyngeal space and its “medial compartment.” We also showed a highly significant correlation between the volume of solution spread and change in NRS.

Feigl et al. [3, 9] reported a regionally confined solution spread when the solution was injected in the parapharyngeal space when a stylopharyngeal fascia was present. We can now confirm these findings of their cadaveric studies as we found the stylopharyngeal fascia in 100% of cases and a regionally confined solution spread when the solution was injected in the parapharyngeal space and its “medial compartment.” As shown in the cadaveric studies, 2 ml of the solution could easily reach the SCG; hence, in a clinical setting, this leads to a decrease in the NRS. The stylopharyngeal fascia is the barrier to the infratemporal and retromandibular fossa. Unfortunately, this stylopharyngeal fascia is inconsistent [10], which may lead to inconstant effects of GLOA at the SCG in patients with trigeminal neuralgia [8, 9, 12, 13].

Furthermore, based on the spread of solution in the area of the SCG, contact of the solution with different anatomical structures and volume of the solution, we estimated a correlation with post-procedural pain scores and side effects. As described above, it was possible to correctly estimate the effects of GLOA at the SCG in 93% (95% CI 68.1–99.8) of cases, which clearly supports the results of cadaveric studies. In 100% of cases, we correctly estimated no minor or major complications.

In two thirds of the interventions reported here, a distinct swelling of the pharyngeal wall was observed after the injection. This led to the hypothesis that the solution may have reached the correct space in front of the prevertebral fascia and that good pain relief should be expected. Unfortunately, no statistical correlation between the swelling and both post-procedural pain scores and volume of solution spread was found. Furthermore, in one intervention, the solution was partially found in the pharyngeal wall and may be a correlated with this post-procedural pharyngeal swelling. No dysphagia was reported in patients with pharyngeal swelling.

Pejic [15] first described the transoral blocking technique of SCG in 1965 in which under direct visual control, the cannula is inserted into the pharyngeal recessus Rosenmüller, in a strictly laterodorsal approach. When the needle is advanced in a more mediodorsal direction, an injection in the prevertebral space is possible. In their cadaveric study, Feigl et al. [3] showed that a more mediodorsal-directed insertion of the needle leads to an increased risk of a possible injection dorsal of the prevertebral fascia, with a resulting failure of the block. In our study, we found no correlation between post-procedural pain scores and different approaches of the needle. Interestingly, a correlation between a strict lateral needle approach and higher volumes of solution spread just fell short of statistical significance. Taken together, these finding lead to the hypothesis that a strict laterodorsal needle direction is preferred to avoid possible block failures; however, further investigations are needed to confirm these findings.

In addition, we found evidence that higher pre-procedural pain intensity is correlated with higher post-procedural pain reduction. It has also been shown that lower post-procedural pain scores increase patient satisfaction. Further effects of GLOA at the SCG on sleep quality, quality of life and patient satisfaction clearly missed reaching statistical significance. Further studies with a larger study population are clearly needed.

There are several important limitations that deserve mention due to the explorative character of this study. First, only limited data are available due to the small study population. While this limitation restricts the number of significant results, the hypothesis cannot be with 100% certainty rejected based on the non-significant results. Secondly, the NRS score of two patients was “0” or “1” before the first intervention, meaning that only slight improvements were possible. These well-known patients of our pain clinic are profiting from a long-term effect of GLOA. As a function of pre-interventional NRS scores, improvements showed an “inclination of distribution.” In general, the statistical methods used take both deviations from the mean and median in both directions into account, which relativizes these findings.

Despite these limitations, we feel that our standardized procedure as well as the separate review of these blinded MRI scans and the correlation with cadaveric studies allow us to make valid clinically relevant conclusions.

Conclusion

As part of a multimodal approach for pain management, GLOA at the SCG is a safe and effective intervention and should be considered for pain treatment in patients suffering from trigeminal neuralgia with high pre-procedural pain scores for example. For the transoral blocking technique, a strict laterodorsal needle direction is recommended to prevent possible block failures due to injection in the prevertebral space, but further investigations are needed to confirm these findings. A total volume of 2 ml injected in the parapharyngeal space and its “medial compartment” is recommended to reach the SCG. Higher volumes may lead to uncontrolled distribution patterns, especially when the stylopharyngeal fascia is absent.