Effect of epidural polydeoxyribonucleotide in a rat model of lumbar foraminal stenosis

Background@#We aimed to investigate the effect of epidural polydeoxyribonucleotide (PDRN) on mechanical allodynia and motor dysfunction in a rat model of lumbar foraminal stenosis (LFS). @*Methods@#This study was conducted in two stages, using male Sprague-Dawley rats. The rats were randomly divided into eight groups. In the first stage, the groups were as follows: vehicle (V), sham (S), and epidural PDRN at 5 (P5), 8 (P8), and 10 (P10) mg/kg; and in the second stage, they were as follows: intraperitoneal PDRN 8 mg/kg, epidural 3,7-dimethyl-1-propargilxanthine (DMPX) (0.1 mg/kg), and DMPX (0.1 mg/kg). The LFS model was established, except for the S group. After an epidural injection of the test solutions, von Frey and treadmill tests were conducted for 3 weeks. Subsequently, histopathologic examinations were conducted in the V, S, P5, and P10 groups. @*Results@#A total of 65 rats were included. The P8 and P10 groups showed significant recovery from mechanical allodynia and motor dysfunction at all time points after drug administration compared to the V group. These effects were abolished by concomitant administration of DMPX. On histopathological examination, no epineurial inflammation or fibrosis was observed in the epidural PDRN groups. @*Conclusions@#Epidural injection of PDRN significantly improves mechanical allodynia and motor dysfunction in a rat model of LFS, which is mediated by the spinal adenosine A2A receptor. The present data support the need for further research to determine the role of epidural PDRN in spinal stenosis treatment.

Effect of epidural polydeoxyribonucleotide in a rat model of lumbar foraminal stenosis

Background@#We aimed to investigate the effect of epidural polydeoxyribonucleotide (PDRN) on mechanical allodynia and motor dysfunction in a rat model of lumbar foraminal stenosis (LFS). @*Methods@#This study was conducted in two stages, using male Sprague-Dawley rats. The rats were randomly divided into eight groups. In the first stage, the groups were as follows: vehicle (V), sham (S), and epidural PDRN at 5 (P5), 8 (P8), and 10 (P10) mg/kg; and in the second stage, they were as follows: intraperitoneal PDRN 8 mg/kg, epidural 3,7-dimethyl-1-propargilxanthine (DMPX) (0.1 mg/kg), and DMPX (0.1 mg/kg). The LFS model was established, except for the S group. After an epidural injection of the test solutions, von Frey and treadmill tests were conducted for 3 weeks. Subsequently, histopathologic examinations were conducted in the V, S, P5, and P10 groups. @*Results@#A total of 65 rats were included. The P8 and P10 groups showed significant recovery from mechanical allodynia and motor dysfunction at all time points after drug administration compared to the V group. These effects were abolished by concomitant administration of DMPX. On histopathological examination, no epineurial inflammation or fibrosis was observed in the epidural PDRN groups. @*Conclusions@#Epidural injection of PDRN significantly improves mechanical allodynia and motor dysfunction in a rat model of LFS, which is mediated by the spinal adenosine A2A receptor. The present data support the need for further research to determine the role of epidural PDRN in spinal stenosis treatment.

Recombinant zoster vaccine (Shingrix®): a new option for the prevention of herpes zoster and postherpetic neuralgia

Postherpetic neuralgia (PHN) is a challenging condition for pain management specialists. The prevention of herpes zoster (HZ) and subsequent PHN in individuals aged 50 years and older, via the development of new vaccines, is an ongoing research project. The live zoster vaccine (LZV, Zostavax®) was the first proof of concept that vaccination could prevent HZ, but LZV cannot be used in various immunecompromised patients. This led to the development of a new non-live recombinant zoster vaccine (RZV, Shingrix®). This RZV has shown promising results in many clinical trials, with high reactogenicity and similar systemic adverse effects compared to those of LZV. The National Advisory Committee on Immunization has recommended LZV as a standard vaccine for HZ prevention in adults ≥ 50 years of age, but no studies directly comparing the safety and efficacy of RZV and LZV vaccines have been conducted. This article reviews the brief history, efficacy, and safety of the two vaccines and discusses the advantage of RZV over LZV based on the available literature.

Increased calcium-mediated cerebral processes after peripheral injury: possible role of the brain in complex regional pain syndrome

Background@#Among various diseases that accompany pain, complex regional pain syndrome (CRPS) is one of the most frustrating for patients and physicians. Recently, many studies have shown functional and anatomical abnormalities in the brains of patients with CRPS. The calcium-related signaling pathway is important in various physiologic processes via calmodulin (CaM) and calcium-calmodulin kinase 2 (CaMK2). To investigate the cerebral mechanism of CRPS, we measured changes in CaM and CaMK2 expression in the cerebrum in CRPS animal models. @*Methods@#The chronic post-ischemia pain model was employed for CRPS model generation. After generation of the animal models, the animals were categorized into three groups based on changes in the withdrawal threshold for the affected limb: CRPS-positive (P), CRPS-negative (N), and control (C) groups. Western blot analysis was performed to measure CaM and CaMK2 expression in the rat cerebrum. @*Results@#Animals with a decreased withdrawal threshold (group P) showed a significant increment in cerebral CaM and CaMK2 expression (P = 0.013 and P = 0.021, respectively). However, groups N and C showed no difference in CaM and CaMK2 expression. @*Conclusions@#The calcium-mediated cerebral process occurs after peripheral injury in CRPS, and there can be a relationship between the cerebrum and the pathogenesis of CRPS.

Topical agents: a thoughtful choice for multimodal analgesia / 대한마취과학회지

For over a thousand years, various substances have been applied to the skin to treat pain. Some of these substances have active ingredients that we still use today. However, some have been discontinued due to their harmful effect, while others have been long forgotten. Recent concerns regarding the cardiovascular and renal risk from nonsteroidal anti-inflammatory drugs, and issues with opioids, have resulted in increasing demand and attention to non-systemic topical alternatives. There is increasing evidence of the efficacy and safety of topical agents in pain control. Topical analgesics are great alternatives for pain management and are an essential part of multimodal analgesia. This review aims to describe essential aspects of topical drugs that physicians should consider in their practice as part of multimodal analgesia. This review describes the mechanism of popular topical analgesics and also introduces the most recently released and experimental topical medications.

Effectiveness of continuous hypertonic saline infusion with an automated infusion pump for decompressive neuroplasty: a randomized clinical trial

BACKGROUND: Hypertonic saline (HS) injections for decompressive neuroplasty (DN) can cause pain. We assessed whether a continuous infusion of HS through an infusion pump would reduce injection-related pain compared with repeated bolus administrations. METHODS: Fifty patients scheduled for DN were randomized to either the bolus injection or the continuous infusion group. After appropriately placing the epidural catheter, 4 mL of 5% NaCl was injected as four boluses of 1 mL each at 15-minute intervals or infused over 1 hour using an infusion pump. The severity of pain induced by HS injection, as measured by the 11-point numerical rating scale (NRS), was the primary outcome. The severity of low back or lower extremity pain, as measured by the 11-point NRS and Oswestry Disability Index (ODI), 3 months following the procedure, was the secondary outcome. RESULTS: Data from 21 patients in the bolus group and 23 in the continuous infusion group were analyzed. No statistically significant difference in injection-related pain was identified between the two groups during the initial HS administration (P = 0.846). However, there was a statistically significant reduction in injection-related pain in the continuous infusion group compared to the bolus injection group from the second assessment onwards (P = 0.001, < 0.001, and < 0.001, respectively). No significant between-group differences in the NRS and ODI scores 3 months post-procedure were noted (P = 0.614 and 0.949, respectively). CONCLUSIONS: Our study suggests that administering HS through a continuous infusion is a useful modality for reducing HS injection-related pain during DN.

Updates to Clinical Information on Anticancer Immunotherapy

OBJECTIVE: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, which have received attention as new anticancer therapeutic agents. METHODS: A literature survey was carried out on PubMed to identify high-impact papers on cancer immunotherapy from 2010. The most recent data on clinical efficacy and safety have been included highlighting the response characteristics to recently approved immunotherapeutic agents. RESULTS: In various cancers, immune checkpoints are a means for cancer cells to evade the immune system. Furthermore, CTLA-4 and PD-L1 can be overexpressed, allowing malignant cells to evade T-cells. Numerous clinical trials have been performed to seek appropriate indication of these products in various cancer types. Among them, the most conspicuous types are melanoma, non-small-cell lung cancer, and head and neck cancer. The approval of ipilimumab by Food and Drug Administration (FDA) commenced a new era of cancer immunotherapy. This was followed by the approval of nivolumab and pembrolizumab. Currently, combination therapies are being investigated for various cancer types. CONCLUSION: In this study, we reviewed recently reported scientific and clinical evidence for currently approved immune checkpoint inhibitors. Although these novel checkpoint inhibitors are ever evolving for cancer therapies, there exist limitations that need to be overcome, indicating the necessity for further studies aiming to improve their efficacy, toxicity, and cost.

The Association between Body Weight Misperception and Psychosocial Factors in Korean Adult Women Less than 65 Years Old with Normal Weight

With society's increasing interest in weight control and body weight, we investigated the association between psychological factors and body image misperception in different age groups of adult Korean women with a normal weight. On a total of 4,600 women from the Korea National Health and Nutrition Examination Survey 2007-2009, a self-report questionnaire was used to assess body weight perception and 3 psychological factors: self-rated health status, stress recognition, and depressed mood. Through logistic regression analysis, a poor self-rated health status (P = 0.001) and a higher recognition of stress (P = 0.001) were significantly associated with body image misperception and this significance remained after controlling for several sociodemographic (Model 1: adjusted odds ratio [aOR], 1.62; 95% confidence interval [CI], 1.31-2.00), health behavior and psychological factors (Model 2: aOR, 1.59; 95% CI, 1.29-1.96; Model 3: aOR, 1.36; 95% CI, 1.01-1.84). Especially, highly stressed middle-aged (50-64 yr) women were more likely to have body image misperception (Model 2: aOR, 2.85; 95% CI, 1.30-6.26). However, the correlation between depressed mood and self-reported body weight was inconsistent between different age groups. In conclusion, self-rated health status and a high recognition rate of severe stress were related to body weight misperception which could suggest tailored intervention to adult women especially women in younger age or low self-rated health status or a high recognition rate of severe stress.

A Direct Inhibitory Effect of Botulinum Toxin Type A on Antral Circular Muscle Contractility of Guinea Pig

PURPOSE: Recent studies suggest new mechanisms of Botulinum toxin (BoNT) other than inhibiting acetylcholine (ACh) release from nerve terminals. The aim of this study was to determine whether other mechanisms for BoNT exist, so that it directly inhibits smooth muscle contraction. MATERIALS AND METHODS: Guinea pig antral muscle strips were studied in vitro after 2 hours of exposure to Botulinum toxin type A (BoNT/A). Contractile responses to electric field stimulation (EFS), high K+ (60 mM) and ACh (100 microM) were evaluated 24 and 48 hours after antral intramuscular injection of BoNT/A or vehicle. RESULTS: BoNT/A inhibited muscular contraction caused by high K+ and ACh. Contractile responses to low (1 & 4 Hz) and high (8 & 20 Hz) frequency EFS of antral muscle strips 24 and 48 hours after antral intramuscular injection of BoNT/A were significantly inhibited. CONCLUSION: The ability of BoNT/A to directly inhibit antral muscular contractility suggests a new mechanism for the pharmacologic actions of BoNT-direct inhibition of muscular contraction.