Inhibitory effect of amenamevir on acute herpetic pain and postherpetic neuralgia in mice infected with herpes simplex virus-1.

BACKGROUND: Amenamevir (AMNV) is a helicase-primase inhibitor with antiviral activity against herpesviruses [herpes simplex viruses (HSV)-1 and -2, and varicella-zoster virus], which are associated with the development of acute herpetic pain (AHP) and postherpetic neuralgia. However, the inhibitory effects of helicase-primase inhibitors on AHP and postherpetic neuralgia remain incompletely understood. OBJECTIVE: In this study, we investigated the effects of AMNV on AHP and postherpetic pain (PHP) in HSV-1-infected mice accompanied by zosteriform-like skin lesions. METHODS: HSV-1 was percutaneously infected on the femoral region of mice. AMNV was orally administered twice a day for 5 days. Pain-related response in the hind paw was evaluated using a paintbrush. The infiltration of inflammatory cells in dorsal root ganglion (DRG) and spinal cord (SC) was evaluated by hematoxylin and eosin staining. The viral load in DRG and the expression of pain-related genes in SC were measured by real-time PCR. RESULTS: Pain response was begun to be observed from day 3 post-infection (pi) in HSV-1-infected mice. AMNV administered repeatedly from day 3 pi or day 4 pi, but not day 5 pi, showed an inhibitory effect on the development of AHP and the transition to PHP. Repeated AMNV administration inhibited inflammatory cell infiltration and increases in the viral load and the expression of pain-related genes (ATF-3, TNF-α, COX-2). CONCLUSION: These results demonstrate that AMNV potently suppresses the development of AHP and the transition to PHP as a consequence of decreased viral load in DRG and reduced expression of pain-related genes in SC.

Delayed Initiation of Supplemental Pain Management is Associated with Postherpetic Neuralgia: A Retrospective Study.

BACKGROUND: Acute pain is a risk factor for developing postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ). Supplemental analgesics are frequently used in the treatment of acute herpetic pain. However, there are insufficient data regarding when to begin supplemental analgesics, and it is unknown whether the delayed use of supplemental analgesics increases the risk of PHN in high-risk patients. OBJECTIVES: This study aimed to evaluate the association between initial time of supplemental pain management and the risk of PHN in high-risk patients. STUDY DESIGN: Retrospective study. SETTING: The Department of Anesthesiology and Pain Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine. METHODS: We performed a retrospective study between May 13, 2017 and August 8, 2018 in our clinic. Multivariable logistic regression analysis was conducted to examine the independent factors associated with PHN. Supplemental pain management was defined as any use of opioids, tricyclic antidepressants, or nerve blocks. A subgroup analysis was conducted in patients who received supplemental pain management within the first 30 days of onset. According to the initial time of supplemental pain management, patients were divided into 2 groups: the early treatment group (<= 14 days), and the late treatment group (> 14 days). The clinical outcomes in these 2 groups was compared for propensity score (PS) matching. RESULTS: A total of 134 patients with HZ aged 50 years or older with moderate to severe pain were enrolled in this study. The delayed initiation of supplemental pain management (> 14 days) (odds ratio, 4.11; 95% confidence interval, 1.69-9.92; P = 0.002) and severity of rash (odds ratio, 2.93; 95% confidence interval, 1.22-7.01; P = 0.016) were independent factors associated with PHN. In the subgroup analysis, after PS matching, there were no significant differences in the baseline clinical parameters between the early and late treatment groups. The incidence of PHN was significantly lower in the early treatment group than the late treatment group (36. 4% vs. 72.7%; P = 0.015). Reduction in pain was also greater in the early treatment group. LIMITATIONS: The findings identified in the present study are specific to the patients who were relatively older and with moderate to severe pain. It is impossible to determine from our study whether younger individuals and individuals with mild acute pain will benefit from early supplemental treatments. Furthermore, because of the retrospective nature of the study, there may be some confounders that could not be controlled. Further prospective studies with larger sample sizes and longer follow-up periods are needed. CONCLUSIONS: The early use of supplemental pain management may decrease the risk of PHN. It might therefore be beneficial to consider administering supplemental pain management earlier in older patients with moderate to severe acute herpetic pain. KEY WORDS: Herpes zoster, postherpetic neuralgia, analgesia, opioid, nerve block, tricyclic antidepressant.

Case report: painful exanthems caused by enterovirus D68 in an adolescent.

RATIONALE: Unlike other enteroviruses which can cause herpangina or hand-foot-and-mouth disease, enterovirus D68 (EV-D68) has usually been linked to respiratory and neurological problems in young children. Skin manifestations had rarely been described in current literatures. PATIENT CONCERNS: We report a 17-year-old girl with fever and painful skin rash over legs and soles for 9 days. Pitting edema was also noted below the knees. There was no respiratory tract or neurological symptoms in this patient. DIAGNOSES: EV-D68 was detected from a throat swab by RT-PCR and confirmed to be subclade B3 by sequencing. INTERVENTIONS: Supportive management. OUTCOMES: The patient was afebrile after 9 days and got full recovery on the 23rd day at outpatient follow-up. LESSONS: To the best of our knowledge, this is the first report of EV-D68 infection with skin manifestations, clinical images, and detailed clinical course. Our findings in this particular case extend the understanding of the disease spectrum.

Transient Receptor Potential Vanilloid-1 in Epidermal Keratinocytes May Contribute to Acute Pain in Herpes Zoster.

The role of transient receptor potential vanilloid-1 (TRPV1) in the initiation of neurogenic inflammation and transduction of pain is well established. In this study 33 patients with herpes zoster (HZ) were recruited from a single centre and underwent a questionnaire interview at their first visit. Punch biopsies from the HZ lesions and the contralateral unaffected skin were performed to localize and quantify the expression of TRPV1. Immunofluorescent staining for TRPV1 was most prominent in the epidermal keratinocytes. Both TRPV1 mRNA and protein levels were significantly higher in the HZ epidermis than in control epidermis (relative ratio 1.62 ± 0.27, p = 0.033 and 2.55 ± 0.51, p = 0.005, respectively). Protein TRPV1 ratio (HZ lesion/control) correlated with the degree of pain (measured on a visual analogue scale; VAS) (p = 0.017) and was significantly lower in patients who had taken either HZ medication or painkillers prior to their visit. These results suggest that non-neuronal TRPV1 may contribute to acute pain in herpes zoster.

Quality of pain in herpes zoster patients.

Pain typically accompanies acute herpes zoster and persists well beyond rash healing. Different types of pain are reported by patients with herpes zoster. Current studies show that these types of pain vary with respect to their presence, location, duration, intensity and quality, hence pain needs to be analyzed more thoroughly. The aim of the study was to assess different components of pain in patients with herpes zoster. The study subjects were 46 patients diagnosed with herpes zoster and selected out of 493 patients treated at the Pain Therapy Clinic, the outpatient facility of Zagreb Clinic for Traumatology, in 2010. Measures used to assess pain and daily activities were the following: SF McGill Pain Questionnaire, Visual Analogue Scale, Self-Assessment of Life Satisfaction, Health Satisfaction and Enjoyment in Life. Analgesic treatment together with demographic and clinical characteristics of patients were also taken into account. The results have shown that the patients report about spontaneous pain mostly in terms of the following qualities of high level pain intensity: throbbing, aching, hot-burning and sharp. The results also demonstrate that herpes zoster pain significantly affects the patients' everyday living quality and their emotional health. Comprehensive assessment of pain is necessary for clinical research about the epidemiology, natural history, pathophysiologic mechanisms, treatment, and prevention of pain in herpes zoster.

Options in topical therapies in the management of patients with acute pain.

The traditional cornerstones of analgesic therapy for patients with acute pain have been oral therapies; however, all oral agents exhibit a variety of potentially dose-limiting or intolerable adverse effects in patients. Elderly patients and those with concomitant conditions already being managed with multiple systemic drugs may be particularly susceptible to systemic toxicities with oral analgesic therapies. Topical agents offer an alternative to oral modalities and can effectively treat patients with acute pain while offering lower systemic absorption and conferring little risk of systemic toxicity. The objective of this article is to review the therapeutic usefulness of available topical therapies in their most thoroughly investigated applications, the treatment of patients with acute musculoskeletal and herpetic pain. For example, although heating pads/wraps and cold packs are widely used to alleviate pain associated with sprains, strains, and contusions, evidence of the effectiveness of these methods is lacking. However, there are sufficient data supporting the use of various topical formulations of nonsteroidal anti-inflammatory drugs (NSAIDs) for these indications (ketoprofen gel or patch, ibuprofen gel or cream, and diclofenac gel or patch), and demonstrating markedly less patient risk of systemic toxicity than is associated with oral NSAID therapy. A ketoprofen patch was shown to be effective and well tolerated in the treatment of patients with tendinopathies. In the treatment of acute neck or low back pain, cold and heat therapies have demonstrated limited effectiveness for patients, and the efficacy of topical NSAIDs has not been established. Use of topical NSAID therapy has been useful in reducing acute-phase herpes zoster pain, and the lidocaine 5% patch has been shown to reduce acute herpetic pain intensity once lesions have healed (the patch cannot be applied to open skin lesions). Topical analgesics represent an alternative treatment modality for patients experiencing acute pain who cannot or choose not to take oral therapies.

Towards evidence based emergency medicine: best BETs from the Manchester Royal Infirmary. BET 3: can pregabalin effectively diminish acute herpetic pain and reduce the incidence of post-herpetic neuralgia?

A short cut review was carried out to establish whether pregabalin can reduce acute herpetic pain and reduce post herpetic neuralgia. 48 papers were found using the reported searches, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. It is concluded that pregabalin does not seem to decrease the intensity of pain related to acute herpes zoster. Moreover, it does not decrease the incidence of post herpetic neuralgia. More research is needed on this topic to clarify this issue [corrected].