Postherpetic neuralgia (PHN) can persist from several months to years after the initial outbreak of herpes zoster (HZ) [1]. Pain originating from PHN can present as burning, sharp, or shooting pain that can be accompanied with paresthesia such as itching, skin crawling [2]. Uncontrolled pain and paresthesia can reduce quality of life in accordance with sleep disturbances, depression, and loss of appetite [3]. Thus, it is essential for patients with PHN to be provided appropriate treatment. Unfortunately, some PHN cases prove to be quite intractable. Therefore, it is imperative to provide PHN patients with prompt and appropriate treatment, however, some PHN cases have proven rather intractable.

Currently, α₂δ ligands, tricyclic antidepressants, serotonin norepinephrine reuptake inhibitors, tramadol, and opioids are used as pharmacological treatment drugs for PHN [4]. However, these drugs have some problems associated with insufficient analgesic effect and adverse drug reactions (ADRs). Accordingly, there has been raised a need for drugs that has an adequate analgesic effect and fewer ADRs.

Mirogabalin besylate (DS-5565, Tarlige^Ⓡ; Daiichi Sankyo Company Limited, Tokyo, Japan) is a novel, voltage-gated calcium channel (VGCC) α₂δ ligand. It was approved in Japan and Korea as a treatment drug for peripheral neuropathic pain including PHN in 2019, 2020 respectively [5,6]. Kato J. conducted randomized, double-blind, placebo-controlled phase 3 study and demonstrated that mirogabalin had a favorable analgesic effect and was well tolerated for the management of PHN in Asian patients [7]. The following case report presents mirogabalin as an alternative novel treatment for refractory PHN.

A 77-year-old male patient with well-controlled hypertension visited our pain clinic for persisting pain on the right side forehead chronic neuralgia for 16 months after being diagnosed with PHN. The patient suffered from intermittent burning pain in the division of ophthalmic branch (V1) of right trigeminal nerve, of a numeric rating of 8 on an 11-point numeric rating scale (NRS; 0 = no pain, 10 = worst pain imaginable) with itching paresthesia, and a sharp and shooting pain occasionally radiating to top of head, with a numeric rating of 9/10. Additionally, he complained of sleep disturbance due to severe pain that continued at night.

In December 2019, before visiting our clinic, patient was diagnosed with HZ of V1 of trigeminal nerve with corresponding dermatomal pain and cutaneous vesicles. The patient was treated with famciclovir for 7 days and medications consisting of pregabalin 75 mg/d, gabapentin 900 mg/d, nortriptyline 10 mg/d, acetaminophen/tramadol 325/37.5 mg/d and lidocaine/prilocaine cream. Skin manifestations were self-limited in its course, although patient then subsequently developed PHN characterized by burning pain and itching paresthesia.

In March 2020, on his first visit to our clinic, pregabalin 150 mg/d, nortriptyline 10 mg/d, acetaminophen/tramadol 325/37.5 mg/d, lidocaine/prilocaine cream was prescribed for 2 weeks as conventional medications, however the patient did not obtain sufficient pain relief. Due to the insufficient analgesic effect, patient received supraorbital and supratrochlear nerve block under ultrasound guidance, and after that his pain score dropped to numeric rating of 5/10.

However, after 3 months, since the intermittent shooting pain and itching sensation were worsened, the patient revisited our clinic. As the pain was not controlled by previously prescribed medications, oxcarbazepine 150 mg/d was added and dosage of pregabalin was increased to 300 mg/d. Additionally Transcutaneous electrical nerve stimulation was performed on trigeminal nerve V1 area.

Despite 6 months of treatment with increasing doses, the patient's burning pain did not subside and the persistent itching caused repeated scratching of the area resulting in scarring. As the patient continued to suffer from poor quality of life, we recommended a neuromodulation such as radiofrequency of the supraorbital nerve, however patient refused due to economic reason. We determined that a medication change was necessary and decided to reduce the dose of pregabalin from 300 mg/d to 150 mg/d while adding 15 mg/d of mirogabalin. After administration of mirogabalin 15 mg/d for four weeks, the patient had no significant side effects except mild peripheral edema but showed a numeric rating of 6 about 30% alleviated and was sometimes free from pain. We increased the dose of mirogabalin to 30 mg/d to further improve the patient’s quality of life, and after 2 weeks, mean daily pain dropped to numeric rating of 4/10 compared with the initial numeric rating of 8-9/10. In addition, the patient’s itching symptoms were significantly reduced, so that the scar from scratching was considerably improved (Fig. 1). As a result, the patient’s drug dosage has been maintained and observed without any significant side effects (Fig. 2).

Figure 1. Patient’s trigeminal nerve V1 dermatomal skin lesion. (A) Before use mirogabalin, (B) after use mirogabalin for 6 weeks.

Figure 2. Patient medication history summary box.

HZ is a viral disease caused by reactivation of latent varicella zoster virus, in cranial nerves or spinal dorsal root ganglia diagnosed by typical dermatomal pain and cutaneous vesicular rash. The incidence of this disease in the United States is estimated to be 3.4 per 1000 persons, increasing significantly after age 50 to 11 per 1000 persons [8]. Most common complication of HZ is PHN. PHN is long-lasting neuropathic pain that persists at least for 3 months after the rash onset. Approximately 10-20% of elder individuals with HZ will develop PHN [8]. Currently, the routine treatment of PHN is multimodal, combining various types of medications, topical formulations and interventional procedures. Pharmacological treatment includes anticonvulsants (e.g., gabapentin, pregabalin), antidepressants (e.g., amitriptyline), opioids (e.g., oxycodone, morphine). Unfortunately, PHN treatment is not always successful, and less than half of patients achieve more than 50% pain relief through these routine pharmacological therapy [9]. Moreover, increasing the dose of the drugs mentioned is often limited by various ADRs such as peripheral edema, nausea, vomiting, drowsiness, especially in elderly patients.

Mirogabalin, a drug newly approved in Korea in 2020, has a high binding affinity for the VGCC α₂δ-1 subunit. Similar to pregabalin and gabapentin, mirogabalin exerts its analgesic effect via binding to the α₂δ-1 subunit, not the α₂δ-2 subunit [10]. Other reports have shown that the α₂δ-1 subunit is associated with induction and maintenance of neuropathic pain, while the α₂δ-2 subunit is related to ataxia, dyskinesia, and absence seizures, respectively [11]. The binding-dissociation kinetic parameters of mirogabalin and pregabalin for the α₂δ-1 and α₂δ-2 subunits were evaluated by in vitro studies. The results suggested that the binding affinities of mirogabalin to the α₂δ-1 and α₂δ-2 subunits were higher than those of pregabalin. Also, mirogabalin has slower dissociation rate for the α₂δ-1 subunit than the α₂δ-2 subunit, while pregabalin has similar dissociation rate for the α₂δ-1 and α₂δ-2 subunit [12]. These results will relate to more sustained analgesic effect of mirogabalin compared with conventional gabapentinoids. Moreover, mirogabalin could be superior in terms of ADRs due to a higher dissociation rate for the α₂δ-2 than α₂δ-1.

In this case, although the patient with PHN at the first branch of trigeminal nerve was administered conventional medications such as pregabalin for over 1 year, the pain was not sufficiently relieved and itching paresthesia did not subside. Since patient refused high-voltage pulsed radiofrequency of the supraorbital nerve that proved effective [13], pharmacologic treatment was the only option. In other study, mirogabalin, was orally administered: 15 mg/d, 20 mg/d, and 30 mg/d in a randomized, double-blind, placebo-controlled phase 3 study on 763 Asian patients with PHN. In the 15 mg/d group and 30 mg/d group, the proportion of patients whose pain decreased by more than 30% compared to the reference pain score was 45.4%, 49.7%, respectively. The proportion of patients who experienced more than 50% of pain reduction in 30 mg/d group was 29.0% [7,14]. Similarly, in the case of our patient, after adding mirogabalin 15 mg/d, the pain was reduced by 30% and after increasing dose to 30 mg/d, reduced by almost 50% (Fig. 3). In addition to relieving pain, the pruritus that caused sleep disturbance was significantly improved, and the quality of life was markedly improved.

Figure 3. Patient’s NRS score trends with treatment changes. NRS, numeric rating scale.

This case report shows that mirogabalin can be a relatively effective and safe treatment for intractable PHN. It may be an alternative treatment for patients who have had ADRs with other drugs or for whom interventional procedure is not possible.

This study was approved by the Institutional Review Board (IRB) of the Seoul National University Hospital (Seoul, Republic of Korea) (IRB no. H-2212-070-1384).

No potential conflict of interest relevant to this article was reported.