Postherpetic neuralgia (PHN) is a type of neuropathic pain caused by the varicella-zoster virus, which can persist long after the characteristic rash has healed. Patients with PHN often report experiencing burning, sharp, or throbbing pain, as well as altered sensations in the area of the affected dermatome. The diagnosis of PHN is made by taking a patient's history, which includes the quality of the pain and any episodes of acute herpetic zoster, and through a physical examination that assesses allodynia, hyper- or hyposensitivity to pain, and the presence of cutaneous scarring in the affected area. Pharmacological interventions, such as topical agents, oral analgesics, tricyclic antidepressants, and anticonvulsants, are the primary methods used to manage pain [1].

Perineural injection therapy (PIT) with 5% dextrose in water (5DW) is thought to inactivate transient receptor potential vanilloid receptor-1 (TRPV-1), an important integrator of responses to inflammatory mediators that is found on peripheral nerves [2-4]. This therapy has been used clinically to treat several common entrapment neuropathies, such as carpal tunnel syndrome, radial nerve palsy, and ulnar neuropathy at the elbow [5]. However, to date, there are no case reports on the use of subcutaneous 5DW injections for the treatment of

Here, we present three cases of PHN where patients experienced significant improvement following ultrasound-guided subcutaneous injections with 5DW.

Ultrasound-guided subcutaneous injections with 5DW were administered to patients with PHN. These patients received the injections directly into the affected areas. We retrospectively analyzed the outcomes for these individuals. A summary of all three cases is presented in Table 1.

The pathophysiology of PHN can be partially attributed to the peripheral sensitization of primary afferent neurons. Fields et al. [6] suggested that for a subset of PHN patients who exhibit allodynia and relatively intact sensation, the pain mechanism may be characterized by an "irritable nociceptor." Pain signals are typically transmitted by unmyelinated C fibers and myelinated Aδ primary afferent neurons. When peripheral nerves are damaged, these neurons may develop pathological ectopic discharges, a reduced threshold for activation by thermal and mechanical stimuli, and an enhanced response to suprathreshold stimulation. These changes contribute to abnormal sensitization and the persistence of chronic neuropathic pain [7]. Experimentally, the in vivo injection of varicella-zoster virus into the footpads of rats has been shown to cause an upregulation of the Na_v1.3 and Na_v1.8 sodium channel subtypes [8]. This upregulation altered the sodium currents in afferent neurons, facilitating high-frequency ectopic firing that is implicated in neuropathic pain [9].

Various conventional treatments for PHN have been extensively studied and are clinically practiced. Antidepressants, anticonvulsants, opioids, and the lidocaine patch are supported by level A evidence, indicating their efficacy is backed by randomized controlled trials. However, a considerable number of patients find systemic therapy intolerable due to adverse effects, including dizziness, somnolence, and dry mouth.

PIT with 5DW for neuropathic pain was first introduced by Lyftogt [10] in 2007. Since then, it has been increasingly utilized to treat a range of peripheral entrapment neuropathies, with its effectiveness supported by a number of studies. For the most common peripheral entrapment neuropathies, carpal tunnel syndrome and ulnar neuropathies at the elbow, this technique has gained acceptance as a standard treatment, with its efficacy confirmed by randomized, double-blind studies. Furthermore, there have been case reports documenting the successful use of PIT with 5DW for various entrapment neuropathies, including radial nerve palsy, supinator syndrome, and meralgia paresthetica [5].

In our patients with PHN, ultrasound-guided subcutaneous injections using 5DW demonstrated efficacy in managing PHN. This was evidenced by a reduction in the VAS score, with initial scores ranging from 5 to 6 and final scores dropping to between 0 and 1. Notably, no minor or major complications were observed in any of the three cases.

Although the precise mechanism of 5DW remains unclear, several potential mechanisms have been proposed. The most widely accepted theory is that 5DW mitigates neurogenic inflammation by inhibiting the capsaicin receptor, TRPV-1, in peripheral nerves. TRPV-1 is a non-selective cation channel found in peripheral nociceptors and is implicated in the development of chronic allodynia and neuropathic pain [2]. Petersen et al. [3] observed that the topical application of capsaicin to the skin of patients with PHN significantly exacerbated pain and allodynia. This effect was particularly pronounced in patients with higher pain scores and preserved thermal sensation [3]. Additionally, mannitol, a sugar molecule structurally akin to dextrose, has been shown to alleviate capsaicin-induced pain when applied topically, according to a randomized controlled trial [4].

Building on previous studies that expected PIT with 5DW to have an effect on TRPV-1 in peripheral nerves, this study focused on TRPV-1 located at the nerve endings of peripheral sensory nerve fibers. TRPV-1 is predominantly found in unmyelinated C fibers and thinly myelinated Aδ fibers, which are responsible for transmitting pain and temperature sensations. The nerve endings of these fibers are situated in the epidermis and dermis. However, due to the considerable pain associated with dermal injections, this study opted for subcutaneous injections of a sufficient volume of 5DW just beneath the dermis. This approach was based on the expectation that the 5DW would disperse through the dermis.

In conclusion, ultrasound-guided subcutaneous injection with 5DW may be regarded as an effective and safe treatment alternative for patients experiencing persistent PHN that is unresponsive to conventional therapies.