Abstract
Background:
Glossopharyngeal neuralgia is a rare cranial neuropathy characterized by paroxysmal, severe pain localized to the sensory distribution of the glossopharyngeal nerve. Diagnostic overlap with trigeminal neuralgia can lead to misclassification and delays in effective management.
Case Report:
We report a 76-year-old female with an 18-year history of right-sided tongue and facial pain initially misdiagnosed as trigeminal neuralgia. Despite undergoing radiotherapy, thermolesion, and microvascular decompression, she experienced recurrent episodes of severe pain. At presentation, she was receiving pregabalin, carbamazepine, and fentanyl transdermal patch with limited efficacy and notable adverse effects. Transition to oxycodone, in combination with optimized pregabalin, carbamazepine, and venlafaxine, led to substantial pain relief and improved functionality. Hyponatremia secondary to high-dose carbamazepine was identified and corrected by dose adjustment.
Conclusion:
This case underscores the diagnostic challenges of glossopharyngeal neuralgia and highlights the importance of individualized, multimodal treatment strategies. While surgical interventions may offer partial benefit, adjunctive pharmacotherapy, including opioid therapy in refractory cases, can be essential for achieving adequate pain control.
Background
Glossopharyngeal neuralgia is a rare cranial neuralgia, accounting for approximately 0.2%-1.3% of all cranial neuralgias, with an estimated incidence of 0.2 to 0.7 per 100 000 persons per year. Clinically, it is characterized by brief, recurrent episodes of severe, typically unilateral pain involving the base of the tongue, tonsillar region, and hypopharynx, often radiating to the ear. Pain is commonly triggered by swallowing, speaking, coughing, or yawning – features that help distinguish it from trigeminal neuralgia which more often involves facial dermatomes and cutaneous triggers.1-3
In some cases, glossopharyngeal neuralgia may be associated with vagal involvement, resulting in autonomic symptoms such as bradycardia, hypotension, or syncope, further aiding differentiation from other cranial neuralgias. The most common etiology is neurovascular conflict, typically involving compression of the glossopharyngeal nerve root entry zone by the posterior or anterior inferior cerebellar artery. Secondary causes include tumors of the cerebellopontine angle, infections, demyelinating disease, trauma, and iatrogenic factors. Recognition of these distinguishing features and underlying causes is essential for accurate diagnosis and appropriate management.1-3
Case Report
The 76-year-old female patient presented to a specialist Pain Management Clinic due to severe pain in the right side of the tongue and gums spreading to the right half of the face, generalized weakness and drowsiness. Patient described pain as stabbing and stinging. Severe pain attacks were triggered by cold drinks and yawning. Constant, stingy pain and severe, stabbing pain attacks deter the patient from drinking any cold fluid. There were no parasympathetic nervous system symptoms such as bradycardia and recurrent syncope. Depressive mood and anhedonia for almost a year were noted at the time of the second visit. The patient also had reduced concentration, reduced self-esteem, and self-confidence. She also experienced reduced appetite. Cranial nerve examination resulted in allodynia on the right gums and the right side of the tongue. No other pathological finding were observed during examination. The patient’s comorbidities included arterial hypertension and dyslipidemia. At first, the aforementioned constant pain was moderate in severity, was mainly experienced on the right side of the face with minor pain on the gums and tongue, and did not impair the patient’s ability to drink cold drinks. After subsequent treatments, the constant pain worsened, and the pain attacks started to appear with more pain experienced in the gums and the tongue. The symptoms including right-sided pain experienced in the tongue, gums, and face appeared 18 years earlier and were managed with the modalities listed below.
Timeline of diagnostic and treatment modalities employed:
2017 – Diagnosis of trigeminal nerve neuralgia based upon clinical presentation and ICHD-3 criteria, radiotherapy of trigeminal nerve – treatment without analgesic effect.
April 2021 – Thermolesion of Gasser’s ganglion, treatment without intended analgesic effect, deterioration to more severe constant pain, and appearance of pain attacks.
June 2021 – Suspicion of glossopharyngeal neuralgia based upon treatment failure and recent appearance of pain attacks, subsequent surgical exploration of the trigeminal nerve and glossopharyngeal nerve for neurovascular conflict, which proved negative for the trigeminal nerve and positive for neurovascular conflict for the glossopharyngeal nerve and posterior inferior cerebellar artery. Microvascular decompression of the lesion and diagnosis of secondary glossopharyngeal neuralgia were made at this time with ICHD-3 criteria. Initiation of carbamazepine monotherapy with a moderate analgesic effect.
2022 – Gamma Knife radiosurgery to the glossopharyngeal nerve – partial control of pain (lower intensity of constant pain, but no improvement in severe pain attacks). Addition of pregabalin and fentanyl transdermal patch.
November 2023 – First visit to the Pain Management Clinic.
At the time of presentation to the Pain Management Clinic, the patient was taking: pregabalin 2 × 75 mg, carbamazepine 2 × 400 mg, 100 µg/h fentanyl transdermal patch, ramipril, pantoprazole and atorvastatin.
Timeline of changes in pharmacological treatment during care in Pain Treatment Clinic:
November 2023 – First visit to the Pain Management Clinic. Magnetic resonance imaging and changes in pharmacological approach. Oxycodone 2 × 5 mg was added, reduction of fentanyl dose to 75 µg/h transdermal patch, carbamazepine dose was increased to 2 × 600 mg, macrogol was added for constipation prophylaxis. Suspicion of a depressive episode was made.
December 2023 – First follow-up visit - reduction of fentanyl dose to 50 µg/h transdermal patch, oxycodone dose increase to 2 × 10 mg, pregabalin dose increase to 2 × 150 mg, diagnosis of moderate depressive disorder based upon ICD-10 criteria, addition of duloxetine 1 × 30 mg, follow-up laboratory tests revealed hyponatremia ( [Na+] = 126 mmol/L) – carbamazepine dose adjusted to 2 × 300 mg, proposal of cannabinoid for multimodal approach.
January 2024 – Second follow-up visit – reduction of fentanyl dose to 25 µg/h transdermal patch, oxycodone dose increase to 2 × 15 mg, duloxetine discontinuation due to poor blood pressure control, sertraline was introduced, follow-up laboratory test resulted in sodium concentration within normal range,
March 2024 – Third follow-up visit – discontinuation of fentanyl, discontinuation of sertraline due to intense pruritus, venlafaxine immediate release 1 × 37.5 mg was added for 5 days with continuation of venlafaxine extended release 1 × 75 mg after 5 days due to depressive disorder, reduction of pregabalin dose to 2 × 75 mg due to reported drowsiness, swelling of the lower limbs, and occasional dizziness.
Venlafaxine was selected as the next-line SNRI, given the patient’s intolerance of duloxetine and sertraline, efficacy in depressive episodes, and established efficacy in neuropathic pain (Table 1).
Summary of Follow-Up Visits and Modification of Pharmacological Management.
Magnetic resonance imaging of the central nervous system in T2 and FIESTA sequence was performed and showed no pathological infiltration along the course of the trigeminal nerve, but revealed a slight thickening of the right glossopharyngeal nerve, most likely due to past decompression as well as some minor chronic vascular lesions. These minor chronic vascular lesions were adjacent to neurovascular contact. The results of magnetic resonance imaging of the cervical spine were consistent with multilevel discopathy in the cervical spine region.
Throughout treatment, the potential for additive sedative effects from pregabalin combined with opioids was closely monitored by regular clinical assessments, patient-reported somnolence tracking, and evaluation of gait stability and cognitive alertness.
The option of introducing cannabinoids was discussed. Cannabinoids were considered because of emerging evidence supporting their use as adjunctive therapy in refractory neuropathic pain, particularly when conventional agents offer partial relief. However, the patient declined their initiation because of her personal beliefs.
Currently, the patient remains free from severe pain episodes and reports no significant adverse effects (somnolence, swelling). The ongoing regimen of oxycodone, adjusted pregabalin, reduced carbamazepine, and venlafaxine provides stable analgesia and improved overall functioning.
Discussion
This case highlights several clinically important challenges in the diagnosis and management of cranial neuralgias, particularly the risk of misclassification between glossopharyngeal neuralgia (GPN) and trigeminal neuralgia (TN). The overlap in paroxysmal pain characteristics, trigger mechanisms, and initial therapeutic response to sodium channel blockers may obscure the correct diagnosis, especially in early stages. In this patient, prolonged pharmacological escalation occurred before definitive recognition of glossopharyngeal nerve involvement, contributing to sustained morbidity. This underscores the importance of meticulous anatomical correlation of pain distribution, careful evaluation of atypical triggers (eg, swallowing, yawning, pharyngeal stimulation), and early targeted imaging to identify secondary causes or neurovascular conflict. Earlier diagnostic clarification may have prompted timelier consideration of surgical options and limited prolonged exposure to suboptimal pharmacotherapy.
Surgical treatment of glossopharyngeal neuralgia is the first-line management for this condition due to secondary causes. Rhizotomy, microvascular decompression and Gamma-Knife radiosurgery are the most common management strategies. In their paper, Lara-Almunia et al showed that Gamma-Knife radiosurgery resulted in statistically significant pain relief (Visual Analog Scale ⩽2) in 75% patients during 1 year after the surgery. Following Gamma-Knife surgery, additional pharmacotherapy was not necessary in 75% of patients. The clinical improvement rate was calculated to be 62.5%. The authors also found that neurovascular conflict and consecutive microvascular decompression in recurrent glossopharyngeal neuralgia was not associated with worse clinical outcome or recurrence of pain after Gamma-Knife radiosurgery. 4 The case provides insight into the sequencing of pharmacological versus surgical interventions in GPN. While pharmacotherapy remains the recommended first-line treatment for primary GPN, secondary forms or refractory cases – particularly those with identifiable neurovascular conflict – may benefit from earlier surgical consultation. Evidence from Gamma-Knife radiosurgery and microvascular decompression suggests meaningful and sustained pain relief in a majority of patients, often with reduced need for ongoing pharmacotherapy. In retrospect, earlier referral for neurosurgical evaluation in this patient may have shortened the duration of severe pain, reduced medication-related adverse effects, and improved overall quality of life. This case, therefore, supports a lower threshold for surgical consideration in patients with inadequate response or intolerance to first-line agents.
Hyponatremia is common in patients receiving carbamazepine. The pathomechanism of this adverse effect is mainly based on inappropriate antidiuretic hormone secretion. The occurrence of this adverse effect ranges between 4.8% and 31.3%. The onset of carbamazepine-induced hyponatremia occurs during the first 3 months of therapy, with a median onset time of 38.5 days. There are known risk factors for this condition, such as age, dose, baseline serum sodium levels and interactions with other drugs. These risk factors can influence the onset time and the severity of carbamazepine-induced hyponatremia. Most of the patients are asymptomatic, but some could present with symptoms such as somnolence and dizziness. Management of this type of hyponatremia typically requires a reduction in drug dose. 5 In the patient’s case, hyponatremia was classified as moderate based upon the listed criteria: (mild – [Na+] = 130-135 mmol/L, moderate – [Na+] = 125-129 mmol/L, severe – [Na+] <125 mmol/L). In the reported case carbamazepine dose was increased to 2 × 600 mg due to growth in the severity of pain and moderate analgesic effect in patient’s case, which resulted in hyponatremia; the sodium concentration decreased from (Na+) = 136 mmol/L at the time of the first visit to (Na+) = 126 mmol/L at the time of the follow-up visit, when generalized weakness also occurred. From a pharmacological standpoint, this case illustrates both the efficacy and limitations of sodium channel blockade in cranial neuralgia. Carbamazepine provided partial pain relief, consistent with its established role as first-line therapy, but was complicated by dose-dependent hyponatremia. The development of symptomatic, moderate hyponatremia necessitated dose reduction and limited its therapeutic potential. Earlier electrolyte monitoring and anticipation of this adverse effect – particularly in dose escalation – might have mitigated morbidity and prompted earlier transition to alternative agents. The subsequent addition of pregabalin, targeting voltage-gated calcium channel–mediated hyperexcitability, resulted in improved pain control, supporting a multimodal, mechanism-based pharmacological approach when monotherapy is insufficient.
Changes in response to chronic irritation are not only reserved for voltage-gated sodium channels. Voltage-gated calcium channels (Cav) are also associated with chronic pain disorders. In normal neurons, voltage-gated calcium channels are responsible for the rhythmicity of neural circuits, neural activation and signal transduction. However, in the case of chronic neuronal stimulation, such as in neurovascular conflict or chemotherapy, overexpression of Cav3.2 in dorsal root ganglia occurs, which results in hyperexcitability of dorsal root ganglia neurons. Those findings led to the use of a new class of drugs in the treatment of neuropathies. Pregabalin, gabapentin and other Cav blockers are drugs that prove to be effective in painful diabetic neuropathy and other types of neurogenic pain. 6 In the case discussed here, pregabalin administration and increased dosage resulted in better control of pain in our patient.
According to Bates et al. opioid analgesics are fifth line therapy in the management of neuropathic pain. 7 Fentanyl is a short-acting opioid receptor agonist, exhibiting a high affinity to µ-type opioid receptor, low affinity to κ-opioid receptor and no affinity to δ-opioid receptor. In contrast, oxycodone binds with very high affinity to µ-type opioid receptors and minimal affinity to κ- and δ-opioid receptors. There is no strong evidence of the efficacy of opioid therapy in patients with neuropathic pain. In a systematic review conducted by Gaskell et al. the authors identified 5 studies investigating the efficacy of modified-release oxycodone therapy in participants with painful diabetic neuropathy or postherpetic neuralgia. Three of those studies found moderate benefit in reducing pain in 44% of the patients, compared to 27% in the placebo group. In all the studies, 87% of patients treated with modified-release oxycodone reported adverse effects such as constipation, nausea, somnolence, vomiting or pruritus, and 4% of the participants had serious adverse effects. One death was reported in the modified-release oxycodone group, but the authors established that it was not linked to therapy. The number needed to treat with modified-release oxycodone was 5.7. 8 A review conducted by Gaskell et al. on the efficacy of fentanyl in neuropathic pain identified 1 clinical trial, in which fentanyl was administered to opioid naïve patients with non-cancer chronic pain by the transdermal route. This study found that 58% of patients treated with fentanyl were “satisfied” or “very satisfied” with pain management. At least one adverse effect was experienced by 86% of patients in the fentanyl group, with serious adverse effects reported in 9.5% of patients in the fentanyl group. One death was noted in this study, but it was not related to treatment. 9 Although opioids should be avoided in the treatment of neuralgia, it could be necessary to use opioid analgesics as a complement to pain therapy. In terms of satisfaction and efficacy of pain management, transdermal fentanyl was superior to modified-release oxycodone (58% vs 44%). The incidence of adverse effects was nearly the same in those studies; however, the double-blinded fentanyl study reported a higher incidence of serious adverse effects. It should be noted that the studies mentioned above were evaluated to be of very low quality. The use of opioids in this case warrants careful consideration. Although opioids are generally discouraged in neuropathic pain and are recommended only as late-line therapy, this case suggests that selected patients with refractory cranial neuralgia may derive limited benefit from cautious opioid use within a closely monitored, multimodal regimen. Indicators supporting opioid consideration in this patient included severe refractory pain despite optimized neuropathic agents, intolerance to higher doses of first-line drugs, and significant functional impairment. The lack of efficacy and intolerable somnolence associated with fentanyl transdermal patch led to its discontinuation, whereas low-dose oxycodone provided improved pain control with fewer adverse effects. This highlights the need for individualized opioid selection, vigilant monitoring for adverse effects, and clear exit strategies when benefit is insufficient. Fentanyl had been introduced earlier because of escalating pain and difficulty maintaining stable analgesia; its rapid onset and strong potency were initially beneficial. However, the patient developed pronounced somnolence and insufficient long-term pain control, prompting consideration of an alternative opioid.
Overall, this case emphasizes that prolonged morbidity in cranial neuralgia may be reduced through earlier diagnostic precision, proactive management of medication-related adverse effects, and timely escalation to combination therapy in refractory or secondary cases. It also reinforces that while opioids should not be routine in neuralgia management, they may serve as a temporary adjunct in carefully selected patients when other options have been exhausted, pending definitive treatment.
This case report is limited by its single-patient design, which restricts the generalizability of the findings. The prolonged 18-year disease course introduces potential recall bias and limits the availability of consistent objective pain and functional assessments across different treatment phases. Additionally, prior surgical and ablative interventions may have influenced pain pathways and subsequent responses to pharmacologic therapy, making it difficult to isolate the specific impact of the revised medication regimen, including opioid use.
Diagnostic confirmation was primarily clinical, without definitive neurophysiological or imaging markers, leaving some degree of diagnostic uncertainty. Finally, the duration of follow-up was limited, precluding assessment of long-term efficacy and safety of the multimodal pharmacologic approach, particularly regarding opioid-related risks.
Conclusion
This case illustrates the diagnostic pitfalls inherent in glossopharyngeal neuralgia, particularly its clinical overlap with other cranial neuralgias, which may delay accurate diagnosis and prolong patient morbidity. Careful attention to pain distribution, triggering factors, and early targeted neuroimaging is essential to distinguish glossopharyngeal neuralgia from trigeminal and other cranial nerve disorders and to identify potentially treatable secondary causes such as neurovascular conflict.
Key therapeutic decision points in this case included recognition of limited efficacy and adverse effects of first-line antiepileptic therapy, timely adjustment of pharmacological agents, and escalation to a multimodal analgesic strategy. While pharmacotherapy remains the initial treatment approach, inadequate response or intolerance should prompt early reconsideration of management, including referral for surgical evaluation rather than prolonged medication escalation.
From a practical clinical perspective, this case supports an individualized, multidisciplinary treatment strategy for refractory glossopharyngeal neuralgia. Combination therapy with antiepileptic drugs and serotonin–norepinephrine reuptake inhibitors may improve pain control, and in carefully selected, closely monitored patients, opioid analgesics such as oxycodone may serve as a short-term adjunct when conventional therapies fail. Early diagnostic clarity and timely therapeutic transitions are critical to minimizing morbidity and optimizing outcomes in this rare but debilitating condition.
Footnotes
Consent to Participate
Written informed consent was obtained from the patient for publication of this case report.
Author Contributions
Robert Maksymowicz: Conceptualization, Methodology, Writing – Original Draft, Writing – Review & Editing, Visualization. Jeremi Jan Matysek: Conceptualization, Writing – Original Draft, Writing – Review & Editing. Dominika Maja Lech: Conceptualization, Writing – Original Draft, Writing – Review & Editing, Project administration. Cyprian Norbert Strączek: Conceptualization, Writing – Original Draft, Writing – Review & Editing. Krzysztof Nosek: Supervision, Writing – Review & Editing, Funding acquisition.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This publication was funded by the internal funds of the University of Warmia and Mazury in Olsztyn.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Data Availability Statement
No new data were created or analyzed in this study. Data sharing does not apply to this article.