Compounded Pain Formulations: What is the Evidence?

Pain syndromes are among the most widespread, costly, and debilitating of all neurological disorders. The number of patients living with chronic pain is expected to increase with the aging population and with the rise in obesity and diabetes across the nation. This type of pain is often insensitive to the traditional pain pharmacopeia or surgical intervention. Over the last 10 years the number of prescriptions that have been compounded by pharmacists has increased dramatically. There are a number of drugs in the area of pain management that have been formulated and compounded by pharmacists to treat conditions such as diabetic neuropathy, fibromyalgia, postherpetic neuralgia, joint pain, arthritis, and a variety of other conditions. A significant portion of these compounded analgesic preparations is made up of topical/transdermal dosage forms such as gels and creams. While the efficacy and doses of these drugs in systemic dosage forms have been widely established, little is known about the permeation and efficacy of these compounds from topical/transdermal gels. This review will provide an overview of chronic pain as a disease, the mechanisms of chronic pain, current treatment approaches to chronic pain, and a discussion of the drugs that are typically compounded into these topical formulations and studied in clinical trials.

Thoracic paravertebral nerve block combined with acupuncture for the treatment of postherpetic neuralgia in the chest and abdomen: A prospective randomized controlled trial.

BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication of varicella-zoster infection and tends to occur in older people. All patients treated with a single regimen have not achieved consistent success across all current study protocols, and multimodal combination regimens still need to be explored. METHODS: A total of 111 patients with PHN were randomly divided into drug group (group A), thoracic paravertebral nerve block group (group B), thoracic paravertebral nerve block combined with acupuncture group (group C), with 37 cases in each group. Group A: received oral gabapentin capsules and external lidocaine gel plaster; group B: combined with thoracic paravertebral nerve block based on group A; group C: combined with acupuncture based on group B. The primary outcome was effective rate, and secondary outcomes included pain sensation score (numerical rating scale), SF-36 quality of life score, and sleep quality. RESULTS: Before treatment, there were no significant differences in numerical rating scale value, SF-36 quality of life score, and sleep quality level among the 3 groups (P > .05). After 12 weeks of treatment, the total effective rate of treatment of patients in group C (91.43%) was higher than that in group B (77.14%), and significantly higher than that in group A (51.43%) (P < .05). CONCLUSION: Based on drug treatment combined with thoracic paravertebral nerve block and acupuncture, the treatment of PHN in the elderly can quickly and effectively relieve pain, improve the quality of life of patients, and improve the quality of sleep.

Transforaminal Epidural Block and Erector Spinae Plane Block to Manage Acute Zoster-Associated Pain: A Retrospective Case-Control Study.

Background and Objectives: Achieving adequate pain reduction in the acute phase of herpes zoster is essential for preventing postherpetic neuralgia (PHN). For this purpose, appropriate antiviral medications, oral analgesic medications, and various nerve block methods could be applied. Erector spinae plane block (ESPB) is a simple, novel ultrasound-guided block technique, and its use has increased because the procedure is convenient and relatively safe. Although several cases have reported the zoster-associated pain (ZAP) control effect of ESPB, the efficacy of ESPB has not been compared with that of other types of nerve blocks for managing ZAP. This study aimed to compare the efficacy of ESPB with that of other types of nerve blocks for managing ZAP. Study Design: Retrospective case-control study. Materials and Methods: Medical records of 53 patients with acute thoracic herpes zoster were reviewed. We divided the participants into two groups: patients who received transforaminal epidural injection (TFEI) (n = 32) and those who received ESPB (n = 21). The efficacy of the procedure was assessed by a numerical rating scale (NRS) and by recording patient medication doses before the procedure and at 1 week, 1 month, 2 months, and 3 months after the procedure. Results: The time required for pain intensity to decrease to NRS ≤ 2 was not significantly different between the groups. The rate of medication discontinuation also was not different between the groups. There was no significant difference between the two groups in the proportion of clinically significant PHN (NRS ≥ 3) at any time point. Limitations: The relatively small sample size from a single center and the retrospective nature of the study served as limitations. Conclusions: The clinical effects of ESPB and TFEI were similar in patients with acute thoracic herpes zoster. ESPB could be considered an interventional option for ZAP management.

Combined effect of Neurotropin® and methylcobalamin on postherpetic neuralgia in mice infected with herpes simplex virus type-1.

BACKGROUND: Postherpetic pain (PHP) is difficult to control. Although Neurotropin® (NTP) and methylcobalamin (MCB) are often prescribed to treat the pain, the efficacy of combined treatment for PHP remains imcompletely understood. OBJECTIVE: In this study, we investigate the combined effects of NTP and MCB on PHP in mice. METHODS: NTP and MCB were administered from day 10-29 after herpes simplex virus type-1 (HSV-1) infection. The pain-related responses were evaluated using a paint brush. The expression of neuropathy-related factor (ATF3) and nerve repair factors (GAP-43 and SPRR1A) in the dorsal root ganglion (DRG) and neurons in the skin were evaluated by immunohistochemical staining. Nerve growth factor (NGF) and neurotrophin-3 (NT3) mRNA expression levels were evaluated using real-time PCR. RESULTS: Repeated treatment with NTP and MCB after the acute phase inhibited PHP. Combined treatment with these drugs inhibited PHP at an earlier stage than either treatment alone. In the DRG of HSV-1-infected mice, MCB, but not NTP, decreased the number of cells expressing ATF3 and increased the number of cells expressing GAP-43- and SPRR1A. In addition, MCB, but not NTP, also increased and recovered non-myelinated neurons decreased in the lesional skin. NTP increased the mRNA levels of NTF3 in keratinocytes, while MCB increased that of NGF in Schwann cells. CONCLUSION: These results suggest that combined treatment with NTP and MCB is useful for the treatment of PHP. The combined effect may be attributed to the different analgesic mechanisms of these drugs.

[Electrical dorsal root ganglion stimulation (DRGS) for the treatment of refractory postherpetic neuralgia]. / Elektricheskaya stimulyatsiya gangliya zadnikh koreshkov spinnogo mozga (DRGS) dlya lecheniya refrakternoi postgerpeticheskoi nevralgii.

Postherpetic neuralgia (PHN) is a rare complication of herpes zoster characterized by prolonged and excruciating pain. Traditional treatments for PHN, such as analgesics, anticonvulsants and antidepressants, do not always bring the desired result. One promising alternative that is attracting the attention of the scientific community is dorsal root ganglion stimulation (DRGS). This method focuses on targeted and precise targeting of the source of pain, providing a new level of effectiveness in the treatment of PHN. OBJECTIVE: A retrospective analysis of the technique and results of implantation of a permanent device for stimulating the spinal ganglia in patients with refractory PHN at the Burdenko Neurosurgical Center. MATERIAL AND METHODS: The study was conducted in 7 patients (5 men, 2 women) with refractory PHN in the period from 2018 to 2020. The age of the patients ranged from 57 to 84 years (average age 74±8.4). All patients were implanted with Boston systems (Precision or Spectra versions). Stimulation parameters: pulse width - 120-210 µs, frequency - 30-130 Hz, amplitude at the lower limit of the appearance of paresthesia with the possibility of increasing with increased pain up to 5 mA. The position of the electrode depended on the location of the pain. All systems were implanted under X-ray guidance. RESULTS: The duration of follow-up observation was more than 2.5 years. The average pain intensity one year after treatment was 3.42±2.45 points on the visual analogue scale (VAS) (a 62.3% decrease in intensity compared to baseline). In 3 (42.8%) patients, the result was characterized by us as «excellent¼ (intensity according to VAS decreased by 75% or more), in 1 (14.2%) - as «good¼ (intensity according to VAS decreased by 50-74%), in 1 (14.2%) - as «moderate¼ (VAS intensity decreased by 25-49% and in 2 (28.5%) as «unsatisfactory¼ (VAS intensity decreased by less than 25%, or postoperative complications occurred). CONCLUSION: Given the complicated nature of PHN, the use of dorsal ganglion stimulation appears to be a promising and innovative treatment approach. Further research is needed to introduce this technique into clinical practice for the treatment of patients suffering from PHN.

Acupoint application for postherpetic neuralgia with qi stagnation and blood stasis and its effect on related inflammatory factors and 5-HT. / ç©´ä½è´´æ•·æ²»ç–—æ°”æ»žè¡€ç˜€åž‹å¸¦çŠ¶ç–±ç–¹åŽé—ç¥žç»ç—›åŠå¯¹ç›¸å ³ç‚Žæ€§å› å­ã€5-HT的影响.

OBJECTIVES: To observe the clinical efficacy of acupoint application in treating postherpetic neuralgia(PHN) with qi stagnation and blood stasis, and its effects on serum inflammatory factors and 5-hydroxytryptamine (5-HT) in patients. METHODS: A total of 136 PHN patients were randomly divided into an observation group (68 cases, 6 case dropped out) and a control group (68 cases, 5 cases dropped out). In the observation group, the combination of swelling-reducing and pain-relieving patches and acupoint application with herbal powder was used at bilateral Sanyinjiao (SP 6), Shenque (CV 8) and ashi points. Sanyinjiao (SP 6) was applied for 30 min per session, once every 7 days; and Shenque (CV 8) and ashi points were applied for 6-8 h per session, once every 1 day. In the control group, mecobalamin injection was administered at Jiaji (EX-B 2) corresponding to the neural segments governing the painful area, 1 mL per injection, once a day. Each treatment course consisted of 7 days, 4 treatment courses were required in both groups. The visual analog scale (VAS) score for pain, 36-item short form health survey (SF-36) score, traditional Chinese medicine syndrome score, and the serum levels of inflammatory factors (monocyte chemoattractant protein-1 [MCP-1], interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α]) and 5-HT were compared in the patients of the two groups before and after treatment, and the clinical efficacy was evaluated. RESULTS: After treatment, the VAS scores, traditional Chinese medicine syndrome scores, serum MCP-1, IL-6, TNF-α, and 5-HT levels were decreased compared with those before treatment in both groups (P<0.05), and the results in the observation group were lower than those in the control group (P<0.05). The SF-36 scores were increased compared with those before treatment in the two groups (P<0.05), and the result in the observation group was higher than that in the control group (P<0.05). The total effective rate of the observation group was 74.2% (46/62), which was higher than 52.4% (33/63, P<0.05) of the control group. CONCLUSIONS: The combination of swelling-reducing and pain-relieving patches and acupoint application with herbal powder has shown better efficacy in treating PHN with qi stagnation and blood stasis, which can significantly alleviate patients symptoms, improve their quality of life, and reduce serum levels of MCP-1, IL-6, TNF-α, and 5-HT.

Efficacy of Paravertebral Injection of Interferon-α2b Combined with High-Voltage, Long-Term Pulsed Radiofrequency in DRG in Mitigation of Postherpetic Neuralgia: A Retrospective Study.

OBJECTIVE: This investigation aims to evaluate the effectiveness of the paravertebral injection of recombinant human interferon-α2b in conjunction with high-voltage, long-term, pulsed radiofrequency (PRF) in the dorsal root ganglion for the mitigation of postherpetic neuralgia (PHN). METHODS: This retrospective study included 84 individuals with acute PHN. The participants were divided into 3 groups. Group H was treated with interferon-α2b combined with high-voltage long-term PRF. Group C was treated with a combination of high-voltage, long-term PRF and a paravertebral injection (without recombinant human interferon-α2b), and group I was treated with interferon-α2b only. All the patients in the 3 groups were orally administered a 5-mg morphine hydrochloride quick-release tablet when a burst of pain occurred during treatment. The numerical rating scale for pain score, the interleukin-6 and galectin-3 levels, and the incidence of PHN were documented before and after therapy. RESULTS: The pain intensity of all individuals decreased after therapy. Compared with group C, the numerical rating scale scores for group H were significantly reduced at 4, 8, and 12 weeks following therapy, and the PHN incidence was significantly lower. Compared with prior treatment, the recommended dosage of gabapentin capsules and immediate-release morphine hydrochloride tablets was reduced for group H. Compared with group C, the requirement for orally administrated gabapentin capsules and morphine hydrochloride tablets in group H was reduced significantly after treatment. No serious adverse reactions occurred in any of the 3 groups. CONCLUSIONS: Within the context of treatment of acute PHN, the injection of interferon-α2b in conjunction with high-voltage, long-term application of PRF is more effective than PRF or the injection of interferon-α2b alone.

Acupoint herbal patching for postherpetic neuralgia: A systematic review and meta-analysis.

BACKGROUND: This study aimed to systematically evaluate the clinical effectiveness and safety of acupoint herbal patching in the treatment of postherpetic neuralgia. METHODS: Eight databases including PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan-Fang Database, China Biomedical Literature Service System, and Chongqing VIP Chinese Science were searched. The search time was set to October 2023. Two researchers independently screened the literature according to the inclusion and exclusion criteria; extracted the basic information, acupoints, Chinese herbal medicine, pain score, sleep score, depression score, and other information of the subjects, and independently assessed the risk of bias by 2 researchers. Meta-analysis of the included studies was performed using the StataMP 16 software. RESULTS: Fifteen studies with 1362 participants were included in this meta-analysis. Ashi is the acupoint frequency at the forefront, and Borneol is the Chinese herbal medicine frequency at the forefront. The acupoint herbal patching group showed significant improvements in visual analog score (SMD: -2.09; 95% Cl: -2.77, -1.42; P < .001), sleep score (SMD: -1.58; 95% Cl: -2.11, -1.05; P < .001), depression score (SMD: -1.61; 95% Cl: -2.22, -0.99; P < .001), Chinese medicine syndrome score (SMD: -2.32; 95% Cl: -2.84, -1.80; P = .06), dermatology life quality index (weighted mean differences: -4.11; 95% Cl: -4.58, -3.63; P = .98), and related laboratory indicators compared to the control group, and the total effective rate was significantly higher (relative risk: 1.20; 95% confidence interval: 1.15, 1.26; P = .99) than the control group. Two studies reported adverse reactions, but the 2 groups were not statistically significant. CONCLUSIONS: Acupoint herbal patching intervention in postherpetic neuralgia is effective in improving the pain, sleep, anxiety, depression, quality of life of patients, and related laboratory indicators.

Corticosteroids for preventing postherpetic neuralgia.

BACKGROUND: Postherpetic neuralgia (PHN) is a common, serious, painful complication of herpes zoster. Corticosteroids have anti-inflammatory properties, and might be beneficial. This is an update of a review first published in 2008, and previously updated in 2013. OBJECTIVES: To assess the effects (benefits and harms) of corticosteroids in preventing postherpetic neuralgia. SEARCH METHODS: We updated the searches for randomised controlled trials (RCTs) of corticosteroids for preventing postherpetic neuralgia in the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, two other databases, and two trials registers (June 2022). We also reviewed the bibliographies of identified trials, contacted authors, and approached pharmaceutical companies to identify additional published or unpublished data. SELECTION CRITERIA: We included all RCTs involving corticosteroids given by oral, intramuscular, or intravenous routes for people of all ages, with herpes zoster of all degrees of severity within seven days after onset, compared with no treatment or placebo, but not with other treatments. DATA COLLECTION AND ANALYSIS: Two review authors independently identified potential articles, extracted data, assessed the risk of bias of each trial, and the certainty of the evidence. Disagreement was resolved by discussion among the co-authors. We followed standard Cochrane methodology. MAIN RESULTS: We identified five trials with a total of 787 participants that met our inclusion criteria. No new studies were identified for this update. All were randomised, double-blind, placebo-controlled parallel-group studies. The evidence is very uncertain about the effects of corticosteroids given orally during an acute herpes zoster infection in preventing postherpetic neuralgia six months after the onset of herpes (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.45 to 1.99; 2 trials, 114 participants; very low-certainty evidence (downgraded for serious risk of bias and very serious imprecision)). The three other trials that fulfilled our inclusion criteria were not included in the meta-analysis because they did not provide separate information on the number of participants with PHN at six months. Adverse events during or within two weeks after stopping treatment were reported in all five included trials. There were no observed differences in serious (RR 1.65, 95% CI 0.51 to 5.29; 5 trials, 755 participants; very low-certainty evidence (downgraded for serious risk of bias and very serious imprecision)), or non-serious adverse events (RR 1.30, 95% CI 0.90 to 1.87; 5 trials, 755 participants; low-certainty evidence (downgraded for serious risk of bias and serious imprecision)) between the corticosteroid and placebo groups. One of these trials was at high risk of bias because of incomplete outcome data, two were at unclear risk of bias, and the other was at low risk of bias. The review was first published in 2008; no new RCTs were identified for inclusion in subsequent updates in 2010, 2013, and 2023. AUTHORS' CONCLUSIONS: Based on the current available evidence, we are uncertain about the effects of corticosteroids given orally during an acute herpes zoster infection on preventing postherpetic neuralgia. Corticosteroids given orally or intramuscularly may result in little to no difference in the risk of adverse events in people with acute herpes zoster. Some researchers have recommended using corticosteroids to relieve the zoster-associated pain in the acute phase of the disease. If further research is designed to evaluate the efficacy of corticosteroids for herpes zoster, long-term follow-up should be included to observe their effect on the transition from acute pain to postherpetic neuralgia. Future trials should include measurements of function and quality of life, as well as updated measures of pain.

[Efficacy and safety of pulsed radiofrequency combined with gabapentin in the treatment of acute herpetic neuralgia].

Objective: To explore the clinical efficacy and safety of pulsed radiofrequency (PRF) combined with gabapentin in the treatment of acute herpetic neuralgia (AHN). Methods: A total of 123 AHN patients were retrospectively selected in Henan Provincial People's Hospital from November 2019 to July 2022, who were divided into two groups based on treatment methods: control group (treated with gabapentin, n=61) and study group (treated with gabapentin and PRF, n=62). The visual analog scale (VAS) was utilized for pain severity assessment and the self-rating scale for sleep (SRSS) was utilized for sleep quality evaluation. The differences in serum levels of interleukin (IL)-10, chemokine ligand 10 (CXCL-10), prostaglandin E2 (PGE2), cyclooxygenase-2 (COX-2), IL-2 and IL-6 before and after treatment were compared between the two groups. The overall treatment effectiveness and the occurrence rates of postherpetic neuralgia and adverse reactions were evaluated in both groups. Results: Among the study group patients, 28 were male and 34 were female, and the age was (62.8±8.5) years. Among the control group patients, 35 were male and 26 were female, and the age was (64.0±7.8) years. The VAS scores of the study group before and after treatment were 7.96±1.33 and 1.52±0.60, respectively, while the control group were 7.68±1.52 and 2.70±0.64. The SRSS scores before and after treatment in the study group were 31.74±5.90 and 12.06±2.81, respectively, while those in the control group were 33.10±5.54 and 14.14±2.96, respectively. Before treatment, there were no statistically differences of the VAS scores and SRSS scores in both groups (all P>0.05). After treatment, the VAS scores and SRSS scores in both groups decreased compared with before treatment (all P<0.05), the study group's VAS scores and SRSS scores were lower than those in the control group (all P<0.05). Before treatment, there were no statistically differences of the serum levels of IL-10, CXCL-10, PGE2, COX-2, IL-2 and IL-6 in both groups (all P>0.05). After treatment, the serum levels of IL-10, CXCL-10, PGE2, COX-2 and IL-6 in both groups decreased compared with before treatment, while the IL-2 level increased. Additionally, the study group had lower serum levels of IL-10, PGE2, COX-2 and IL-6 compared with the control group (all P<0.05). After treatment, the study group had 35 cases of cure, 26 cases of effectiveness, and 1 case of ineffectiveness, while the control group had 22 cases of cure, 31 cases of effectiveness, and 8 cases of ineffectiveness. The overall treatment efficacy of the study group was better than that of the control group (P=0.012). The incidence of postherpetic neuralgia in the study group after treatment was 16.1% (10/62), which was lower than that in the control group, which was 37.7% (23/61) (P<0.05). There were no statistically differences of the occurrence rates of adverse reactions in both groups (all P>0.05). Conclusion: Combining PRF with gabapentin for the treatment of AHN demonstrates better overall efficacy and safety, which can more effectively alleviate pain, improve sleep, and reduce inflammatory cytokine levels.

Effect of antivirals plus low-dose, short-term glucocorticoids on post-herpetic neuralgia.

BACKGROUND: Post-herpetic neuralgia (PHN) is the most common complication of herpes zoster (HZ). It is unclear whether short-term and low-dose glucocorticoids combined with antivirals can reduce the incidence of PHN. OBJECTIVES: To investigate the effects of antivirals plus low-dose, short-term glucocorticoids on PHN. MATERIALS & METHODS: A total of 394 patients with HZ were divided into glucocorticoid and non-glucocorticoid groups, and the incidence of PHN was studied retrospectively. Forty patients with HZ were randomized into the glucocorticoid (n=20) and non-glucocorticoid (n=20) groups. The levels of protein 100-B (S100B) and neuron-specific enolase (NSE) in the blood and the viral load in the skin lesions were measured before and after seven days of treatment. Patient condition and pain were assessed using the HZ and visual analogue scale pain scores. RESULTS: The incidence of PHN in the glucocorticoid and non-glucocorticoid groups was 20.89% and 30.51%, respectively. In patients with onset time >seven days before treatment, the incidence of PHN was 19.81% and 40.16%, respectively. In the glucocorticoid group, after treatment, the mean serum NSE level of the glucocorticoid group decreased from 15.8 ng/mL to 14.0 ng/mL, while the mean serum S100B level decreased from 1486.3 ng/mL to 1453.7 ng/mL. There was no intergroup difference in the reduction rate of viral load. The mean condition score and pain score were significantly lower in the glucocorticoid group. CONCLUSION: Antiviral therapy plus low-dose, short-term glucocorticoids can improve the condition of patients with HZ and partly reduce the incidence of PHN.

The effectiveness of the erector spinae plane block using methylprednisolone and bupivacaine in post-herpetic neuralgia: Case series.

Post-herpetic neuralgia (PHN) is the most common chronic complication of herpes zoster and the most common pain syndrome associated with infections. There are medical and interventional treatment options in PHN, and some patients may be resistant to the preferred medical treatments. This situation negatively affects the quality of life of the patient. Interventional treatments come to the fore, especially in patients in whom medical treatments are not sufficient, and systemic side effects such as hepatotoxicity and nephrotoxicity occur. Erector spinal plane block (ESPB) is a recently described ultrasound-guided regional anesthesia technique. It is especially used to prevent post-operative pain due to trunk surgeries. In this study, ESPB was administered with methylprednisolone and bupivacaine in five patients who developed PHN after thoracic herpes zoster and did not have an expected response to three-month medical treatments. Pain severity was assessed using the Numerical Pain Rating Scale. We want to emphasize that ESPB, which is applied with steroids and anesthetics, is a speedy and longacting treatment option that increases the quality of life of the patient, has low side effects, and is a cost-effective treatment option.

A Network Meta-Analysis of Randomized Clinical Trials to Assess the Efficacy and Safety of Antiviral Agents for Immunocompetent Patients with Herpes Zoster-Associated Pain.

BACKGROUND: The most refractory symptom of herpes zoster (HZ) is pain. Approximately 90% of people who have HZ suffer from pain. Early use of antiviral medications has been found to reduce pain across all stages of the disease. Although many antiviral agents via oral or intravenous administration were recommended by clinical practice, the best approach to prevent HZ-associated pain remains uncertain. OBJECTIVES: The purpose of this study was to compare the efficacy and adverse events of various antiviral agents used for the treatment of HZ-associated pain through a network meta-analysis. STUDY DESIGN: A systematic review and meta-analysis. SETTING: The Cochrane Register of Controlled Trials, Embase, and PubMed were searched from inception to Feb 2020. METHODS: Randomized clinical trials evaluating antiviral agents currently available for treating HZ-associated pain were included. We extracted data in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and conducted network meta-analyses with random-effects models. The primary outcome was the presence of acute pain at the end of anti-virus treatment, and the secondary outcomes included the presence of pain at 28-30 days after the onset of the acute herpetic rash, the presence of postherpetic neuralgia (PHN), and any other adverse events. RESULTS: A total of 17 randomized control trials with 5,579 participants were included in this study. According to the results of the network meta-analysis, for the treatment of acute pain, there was no significant difference between oral acyclovir and intravenous acyclovir. Furthermore, oral famciclovir was the most effective treatment concerning both the odds ratio (OR) (superior to placebo OR = 0.25; 95% CI: 0.13~0.48) and the surface under the cumulative ranking curve (SUCRA) values of 0.84 for the treatment of acute pain among all the oral antiviral agents. For the presence of pain at 28-30 days, no significant difference was observed in efficacy between all antiviral treatments and placebo concerning the OR; however, oral valaciclovir ranked first (SUCRA values of 0.96). For the presence of NPH, oral famciclovir was determined to be the most effective (SUCRA values of 0.77) treatment with an efficacy of 0.42 (95% CI: 0.18~0.99) versus placebo. For adverse events, there was no significant difference between oral antivirals and placebo; however, intravenous acyclovir ranked last with a score of OR 4.31 (95% CI: 1.26~14.75) versus placebo. LIMITATIONS: The distribution of severity of pain was different in various studies; then, the lack of availability of individual data prevented us from analyzing the effects of the risk factors. CONCLUSIONS: For the treatment of acute pain and PHN, oral famciclovir was the most effective treatment among all the oral antiviral agents. For alleviating pain after 28-30 days, oral valaciclovir appeared to be the most effective among all antiviral agents. Additionally, all oral antiviral agents were well tolerated. CLINICAL TRIAL REGISTRATION INFORMATION: PROSPERO under the identification CRD42020212834.

Investigational Drugs for the Treatment of Postherpetic Neuralgia: Systematic Review of Randomized Controlled Trials.

The pharmacological treatment of postherpetic neuralgia (PHN) is unsatisfactory, and there is a clinical need for new approaches. Several drugs under advanced clinical development are addressed in this review. A systematic literature search was conducted in three electronic databases (Medline, Web of Science, Scopus) and in the ClinicalTrials.gov register from 1 January 2016 to 1 June 2023 to identify Phase II, III and IV clinical trials evaluating drugs for the treatment of PHN. A total of 18 clinical trials were selected evaluating 15 molecules with pharmacological actions on nine different molecular targets: Angiotensin Type 2 Receptor (AT2R) antagonism (olodanrigan), Voltage-Gated Calcium Channel (VGCC) α2δ subunit inhibition (crisugabalin, mirogabalin and pregabalin), Voltage-Gated Sodium Channel (VGSC) blockade (funapide and lidocaine), Cyclooxygenase-1 (COX-1) inhibition (TRK-700), Adaptor-Associated Kinase 1 (AAK1) inhibition (LX9211), Lanthionine Synthetase C-Like Protein (LANCL) activation (LAT8881), N-Methyl-D-Aspartate (NMDA) receptor antagonism (esketamine), mu opioid receptor agonism (tramadol, oxycodone and hydromorphone) and Nerve Growth Factor (NGF) inhibition (fulranumab). In brief, there are several drugs in advanced clinical development for treating PHN with some of them reporting promising results. AT2R antagonism, AAK1 inhibition, LANCL activation and NGF inhibition are considered first-in-class analgesics. Hopefully, these trials will result in a better clinical management of PHN.

Role of autophagy in the pathogenesis and regulation of pain.

Pain is a ubiquitous and highly concerned clinical symptom, usually caused by peripheral or central nervous injury, tissue damage, or other diseases. The long-term existence of pain can seriously affect daily physical function and quality of life and produce great torture on the physiological and psychological levels. However, the complex pathogenesis of pain involving molecular mechanisms and signaling pathways has not been fully elucidated, and managing pain remains highly challenging. As a result, finding new targets to pursue effective and long-term pain treatment strategies is required and urgent. Autophagy is an intracellular degradation and recycling process that maintains tissue homeostasis and energy supply, which can be cytoprotective and is vital in maintaining neural plasticity and proper nervous system function. Much evidence has shown that autophagy dysregulation is linked to the emergence of neuropathic pain, such as postherpetic neuralgia and cancer-related pain. Autophagy has also been connected to pain caused by osteoarthritis and lumbar disc degeneration. It is worth noting that in recent years, studies on traditional Chinese medicine have also proved that several traditional Chinese medicine monomers involve autophagy in the mechanism of pain relief. Therefore, autophagy can serve as a potential regulatory target to provide new ideas and inspiration for pain management.

Effect of extracorporeal shock wave combined with pregabalin on patients with post-herpetic neuralgia.

Post-herpetic neuralgia (PHN) is a chronic pain that is difficult to treat and lasts a long time, which poses a threat to patients' physical and mental health (MH) and quality of life. To analyze the effectiveness of extracorporeal shock wave (ESW) combined with pregabalin on PHN and its impact on PHN patients' quality of life with the help of a random number table. Totally 164 PHN patients were assigned to a control group (n = 82) or an observation group (n = 82). The observation group was given pregabalin combined with ESW treatment, while the control group was only given pregabalin. In the 2 groups, the general clinical data of the patients were compared. The inflammation levels including erythrocyte sedimentation rate (ESR), CRP, lymphocyte count and albumin level in both groups were compared prior to and following therapy. In addition, the difference between pretreatment and post-treatment in the 2 groups was compared with respect to neuralgia and quality of life. After treatment, the observation group exhibited much lower ESR and CRP but quite higher lymphocyte count and albumin level relative to the control group (P < .05). Additionally, the improvement in visual analogue scale (VAS) scores and short form 36 (SF-36) scale scores including role-emotional (RE), MH, physical function (PF), general health (GH), bodily pain (BP), social function (SF), vitality (VT), and role-physical (RP) scores in the 2 groups were pronounced following treatment, which was more apparent in the observation group (P < .05). The combination of ESW with pregabalin can reduce the inflammation, improve the quality of life of PHN patients and effectively relieve their neuralgia.

Clinical efficacy of LED golden light combined with acyclovir in the treatment of herpes zoster: a single-center prospective study.

This study aimed to explore the safety and clinical efficacy of light emitting diode (LED) golden light combined with acyclovir in treating herpes zoster (HZ). According to the random number table, 54 inpatients with HZ were divided into control group, golden-light group, and red-light group, with 18 cases in each group. The control group received acyclovir intravenous drip, while the patients in the red-light group received acyclovir intravenous drip and red-light LED phototherapy, and the golden-light group received acyclovir intravenous drip and golden-light LED phototherapy. Primary assessments included herpes stopping time, incrustation time, decrustation time, pain visual analog scale scores (VAS), and incidence of postherpetic neuralgia (PHN) on the 30th and 90th days. Golden-light group and red-light group showed a shorter herpes stopping time, incrustation time, and decrustation time (P < 0.05) compared to the control group (P < 0.05), while the golden-light group showed a shorter incrustation time and decrustation time than the red light group (all P < 0.05). After treatment VAS scores, the golden-light group showed a significant improvement compared to the control group. The golden-light group showed a better PHN incidence than the control group at 30 days follow-up. Compared with the comprehensive curative effect, the total effective rates of the golden-light group, red-light group, and control group were 88.89%, 77.78%, and 72.22%, respectively, and the efficacy of the golden-light group was better than that of the control group and red-light group. Golden light combined with acyclovir can shorten the course of HZ, relieve pain, and reduce the occurrence of PHN, and the effect is better than that of the red-light group and the control group.

Efficacy and safety of pulsed radiofrequency combined with pregabalin for herpetic neuralgia: A systematic review and meta-analysis.

BACKGROUND: Pulsed radiofrequency (PRF), as a new technique, is used to treat a variety of chronic pain syndromes, but it has a high recurrence rate for herpetic neuralgia and is often combined with drugs therapy. The aim of this study was to comprehensively evaluate the efficacy and safety of PRF combined with pregabalin in the treatment of herpetic neuralgia. METHODS: The electronic databases, including CNKI, Wanfang data, PubMed, Embase, web of science, and Cochrane Library were searched from inception to January 31, 2023. The outcomes were pain scores, sleep quality and side effects. RESULTS: Fifteen studies with 1817 patients were included in this meta-analysis. PRF combined with pregabalin significantly reduced the visual analogue scale/score in patients with postherpetic neuralgia or herpes zoster neuralgia when compared with pregabalin or PRF monotherapy [P < .00001, standardized mean difference (SMD) = -2.01, confidence intervals (CI) = -2.36 to -1.66; P < .00001, SMD = -0.69, CI = -0.77 to -0.61]. Compared with pregabalin monotherapy, PRF combined with pregabalin significantly decreased the pittsburgh sleep quality index score, the dosage and number of days of using pregabalin (P < .00001, SMD = -1.68, CI = -2.19 to -1.17; P < .00001, SMD = -0.94, CI = -1.25 to -0.64; P < .00001, SMD = -1.52, CI = -1.85 to -1.19). However, there was no significant difference in the effect of PRF combined with pregabalin versus PRF alone on pittsburgh sleep quality index score in patients with postherpetic neuralgia (P = .70, SMD = -1.02, CI = -6.11 to 4.07). In addition, PRF combined with pregabalin could significantly decrease the incidence of dizziness, somnolence, ataxia and pain at puncture site when compared with pregabalin monotherapy (P = .0007, odds ratio [OR] = 0.56, CI = 0.40 to 0.78; P = .008, OR = 0.60, CI = 0.41 to 0.88; P = .008, OR = 0.52, CI = 0.32 to 0.84; P = .0007, OR = 12.39, CI = 2.87 to 53.43), but no significant difference was observed when compared with PRF alone. CONCLUSIONS: PRF combined with pregabalin can effectively alleviate the pain intensity and improve sleep quality in patients with herpetic neuralgia, and the incidence of complications was low, so it was worthy of clinical application.

Cutaneous nerve fiber and peripheral Nav1.7 assessment in a large cohort of patients with postherpetic neuralgia.

ABSTRACT: The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with pain level. We report results of skin biopsies and correlations with baseline pain scores, mechanical hyperalgesia, and the Neuropathic Pain Symptom Inventory (NPSI) in 294 patients who participated in a clinical trial of TV-45070, a topical semiselective sodium 1.7 channel (Nav1.7) blocker. Intraepidermal nerve fibers and subepidermal Nav1.7 immunolabeled fibers were quantified in skin punch biopsies from the area of maximal PHN pain, as well as from the contralateral, homologous (mirror image) region. Across the entire study population, a 20% reduction in nerve fibers on the PHN-affected side compared with that in the contralateral side was noted; however, the reduction was much higher in older individuals, approaching 40% in those aged 70 years or older. There was a decrease in contralateral fiber counts as well, also noted in prior biopsy studies, the mechanism of which is not fully clear. Nav1.7-positive immunolabeling was present in approximately one-third of subepidermal nerve fibers and did not differ on the PHN-affected vs contralateral sides. Using cluster analysis, 2 groups could be identified, with the first cluster showing higher baseline pain, higher NPSI scores for squeezing and cold-induced pain, higher nerve fiber density, and higher Nav1.7 expression. While Nav1.7 varies from patient to patient, it does not seem to be a key pathophysiological driver of PHN pain. Individual differences in Nav1.7 expression, however, may determine the intensity and sensory aspects of pain.