Comparison of Polynucleotide, Sodium Hyaluronate, and Crosslinked Sodium Hyaluronate for the Management of Painful Knee Osteoarthritis: A Multi-Center, Randomized, Double-Blind, Parallel-Group Study.

OBJECTIVE: To compare the clinical effectiveness of sodium polynucleotide, classic hyaluronic acid, and crosslinked hyaluronic acid for the management of painful knee osteoarthritis. DESIGN: Randomized, double-blind, parallel-group clinical trial. SETTING: Multicenter study. SUBJECTS: Patients with chronic painful knee osteoarthritis. METHODS: Ninety patients were selected and randomized into polynucleotide, classic hyaluronic acid, and crosslinked hyaluronic acid groups (30 per group). Intra-articular injections of the viscosupplement for each group were administered to the patients three times at one-week intervals. The primary outcome was differences in changes of weight-bearing pain scores at 16 weeks between the groups. The secondary outcomes were changes in the intensity of knee pain during weight-bearing, walking, and rest, and functional disability, quality of life, and adverse events during the 16-week follow-up period. RESULTS: At 16 weeks, the polynucleotide group showed a higher reduction in pain score using a Visual Analog Scale score (0-100) than the classic hyaluronic acid (-17.6 [95% CI = -35.1 to -0.1]; P = .048) and crosslinked hyaluronic acid (-22.4 [95% CI = -41.5 to -3.3]; P = .016) groups. The polynucleotide and crosslinked hyaluronic acid groups showed an early-onset reduction in knee pain during weight-bearing, walking, and rest. All three groups showed reductions in functional disability and improved quality of life at 16 weeks without inter-group differences. No severe adverse events were reported throughout the study period. CONCLUSION: Polynucleotide significantly relieves pain more and relieves pain faster in patients with knee osteoarthritis than classic and crosslinked hyaluronic acid, with improved health-related quality of life.

The Use of Contrast Agents in Interventional Pain Procedures: A Multispecialty and Multisociety Practice Advisory on Nephrogenic Systemic Fibrosis, Gadolinium Deposition in the Brain, Encephalopathy After Unintentional Intrathecal Gadolinium Injection, and Hypersensitivity Reactions.

This Practice Advisory presents a comprehensive and evidence-based set of position statements and recommendations for the use of contrast media in interventional pain procedures. The advisory was established by an international panel of experts under the auspices of 11 multinational and multispecialty organizations based on a comprehensive review of the literature up to December 31, 2019. The advisory discusses the risks of using gadolinium-based contrast agents. These include nephrogenic systemic fibrosis, gadolinium brain deposition/retention, and encephalopathy and death after an unintentional intrathecal gadolinium injection. The advisory provides recommendations on the selection of a specific gadolinium-based contrast agent in patients with renal insufficiency, those who had multiple gadolinium-enhanced magnetic resonance imaging examinations, and in cases of paraspinal injections. Additionally, recommendations are made for patients who have a history of mild, moderate, or severe hypersensitivity reactions to contrast medium.

Monocyte chemoattractant protein-1 immunoreactivity in sensory ganglia and hindpaw after adjuvant injection.

Monocyte chemoattractant protein-1 (MCP-1)/CCL2 is a member of the CC chemokine family that exhibits potent chemotactic activity for monocytes/macrophages. In the current study, the proportion of monocyte chemoattractant protein-1-immunoreactive (IR) neurons in the dorsal root ganglion (DRG) of rats was shown to increase markedly following adjuvant injection into the hindpaw. MCP-1-IR axon terminals were not found in the spinal cord or hindpaw of control or adjuvant-treated rats. Instead, the inflamed hindpaw dermis was infiltrated by numerous MCP-1-IR inflammatory cells. Following adjuvant injection, the majority of MCP-1-IR neurons in the DRG colocalized with IB4 binding. Our findings suggest that peripheral tissue inflammation induces increased MCP-1 expression in DRG neurons and this may be dependent upon glial cell line-derived neurotrophic factor.

Usefulness of Inflammatory Markers for the Prediction of Postherpetic Neuralgia in Patients with Acute Herpes Zoster.

BACKGROUND: Increasing evidence suggests a pivotal role for neuronal inflammation in response to replicating varicella zoster virus in the development of postherpetic neuralgia (PHN). OBJECTIVE: In this study, we investigated the value of serum levels of various inflammatory markers in acute herpes zoster (HZ) as predictors for the development of PHN. METHODS: A total of 116 patients with acute HZ were enrolled in this study. We measured scores on the pain visual analogue scale (VAS) at baseline and at 1, 3, and 6 months after diagnosis of HZ. We defined PHN as pain greater than 1 on the VAS lasting for more than 6 months. Serum samples for laboratory assay, including complete blood count were obtained at the initial visit. Correlations between the levels of each inflammatory marker and the development of PHN were evaluated. RESULTS: Levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), lymphocyte count, and albumin showed significant correlations with development of PHN in univariate analysis. Levels of ESR, CRP, and lymphocyte count also showed significant correlations in multivariate analysis. ESR level showed stronger correlations with development of PHN than levels of CRP and lymphocyte count. CONCLUSION: In this study, we confirmed that elevated ESR was an independent and significant predictor of PHN in patients with acute HZ. To validate these results, further well-designed, randomized clinical trials are needed.

Prophylactic antiemetic effect of midazolam after middle ear surgery.

OBJECTIVE: To investigate the prophylactic antiemetic effect of midazolam after middle ear surgery. STUDY DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SUBJECTS AND METHODS: Ninety women patients undergoing middle ear surgery with general anesthesia received intravenously either midazolam 0.075 mg/kg or normal saline (n = 45 each) after induction of anesthesia. The incidence and severity of postoperative nausea and vomiting, rescue antiemetics, pain intensity, and side effects such as headache, dizziness, and drowsiness were assessed during the first 24 hours after anesthesia. RESULTS: Midazolam groups showed total incidence and severity of nausea and vomiting. Patients who required rescue antiemetics were significantly lower than in saline group (P < 0.05), but there were no significant differences in pain intensity and side effects such as headache, dizziness, and drowsiness between groups. CONCLUSIONS: Midazolam 0.075 mg/kg is effective for reducing nausea and vomiting after middle ear surgery.

Psoas compartment block for treatment of motor weakness and pain following herpes zoster.

Reactivation of the latent varicella zoster virus in the sensory ganglion causes herpes zoster (HZ). Its characteristic symptom is a painful rash in the involved dermatome. HZ-induced motor weakness is rare and is usually resolved within one year of the onset, but some patients permanently experience motor dysfunction. Epidural steroid administration, with antiviral therapy, can be effective in treating pain from HZ and preventing postherpetic neuralgia. But an epidural block is contraindicated in patients receiving thromboprophylaxis. A psoas compartment block (PCB) provides equivalent analgesic efficacy with significantly low incidence of complication, compared to an epidural block. A 68 year old male patient recieving thromboprophylaxis presented with motor weakness following painful rash in his left L4 dermatome. Ten days before presentation, herpetic rash occurred on his left leg. We performed PCB with a steroid and local anesthetic, which successfully and safely alleviated the pain and motor weakness from HZ.

Neurogenic muscle hypertrophy: a case report.

Muscular hypertrophy is caused mainly due to myopathic disorder. But, it is also rarely produced by neurogenic disorder. A 74-year-old woman complained of right calf pain with hypertrophy for several years. Recent lumbar spine magnetic resonance imaging (MRI) showed central and lateral canal narrowing at the L4-L5 intervertebral space. Lower extremity MRI revealed fatty change of right medial head of the gastrocnemius and soleus, causing right calf hypertrophy. Electrodiagnostic examinations including electromyography and nerve conduction velocity testing demonstrated 5th lumbar and 1st sacral polyradiculopathy. Integrating all the results, the diagnosis was neurogenic muscle hypertrophy. Neurogenic muscle hypertrophy is very rare, but we recommend that clinicians consider this problem when a patient complains of lower limb hypertrophy and pain.

Effects of bispectral index monitoring as an adjunct to nurse-administered propofol combined sedation during colonoscopy: a randomized clinical trial.

BACKGROUND/AIMS: The efficacy of bispectral index (BIS) monitoring during colonoscopic sedation is debated. We aimed to determine whether BIS monitoring was useful for propofol dose titration, and to evaluate differences in sedative administration between expert and inexperienced medical personnel during colonoscopy procedures that required moderate sedation. METHODS: Between February 2012 and August 2013, 280 consecutive patients scheduled to undergo a screening colonoscopy participated in this study and were randomly allocated to the expert or inexperienced endoscopist group. Each group was further divided into either a BIS or a modified Observer's Assessment of Alertness/Sedation Scale (MOAA/S) subgroup. Trained nurses administered combined propofol sedation and monitored sedation using either the BIS or MOAA/S scale. RESULTS: The mean BIS value throughout the procedure was 74.3 ± 6.7 for all 141 patients in the BIS group. The mean total propofol dose administered in the BIS group was higher than that in the MOAA/S group, independently of the endoscopists' experience level (36.9 ± 29.6 and 11.3 ± 20.7, respectively; p < 0.001). The total dose of propofol administered was not significantly different between the inexperienced endoscopist group and the expert endoscopist group, both with and without the use of BIS (p = 0.430 and p = 0.640, respectively). CONCLUSIONS: Compared with monitoring using the MOAA/S score alone, BIS monitoring was not effective for titrating the dose of propofol during colonoscopy, irrespective of colonoscopist experience.

Herpes Zoster and Postherpetic Neuralgia: Practical Consideration for Prevention and Treatment.

Herpes zoster (HZ) is a transient disease caused by the reactivation of latent varicella zoster virus (VZV) in spinal or cranial sensory ganglia. It is characterized by a painful rash in the affected dermatome. Postherpetic neuralgia (PHN) is the most troublesome side effect associated with HZ. However, PHN is often resistant to current analgesic treatments such as antidepressants, anticonvulsants, opioids, and topical agents including lidocaine patches and capsaicin cream and can persist for several years. The risk factors for reactivation of HZ include advanced age and compromised cell-mediated immunity (CMI). Early diagnosis and treatment with antiviral agents plus intervention treatments is believed to shorten the duration and severity of acute HZ and reduce the risk of PHN. Prophylactic vaccination against VZV can be the best option to prevent or reduce the incidence of HZ and PHN. This review focuses on the pathophysiology, clinical features, and management of HZ and PHN, as well as the efficacy of the HZ vaccine.

Spinal Gap Junction Channels in Neuropathic Pain.

Damage to peripheral nerves or the spinal cord is often accompanied by neuropathic pain, which is a complex, chronic pain state. Increasing evidence indicates that alterations in the expression and activity of gap junction channels in the spinal cord are involved in the development of neuropathic pain. Thus, this review briefly summarizes evidence that regulation of the expression, coupling, and activity of spinal gap junction channels modulates pain signals in neuropathic pain states induced by peripheral nerve or spinal cord injury. We particularly focus on connexin 43 and pannexin 1 because their regulation vastly attenuates symptoms of neuropathic pain. We hope that the study of gap junction channels eventually leads to the development of a suitable treatment tool for patients with neuropathic pain.

Detection Rate of Intravascular Injections during Cervical Medial Branch Blocks: A Comparison of Digital Subtraction Angiography and Static Images from Conventional Fluoroscopy.

BACKGROUND: The most definitive diagnosis of neck pain caused by facet joints can be obtained through cervical medial branch blocks (CMBBs). However, intravascular injections need to be carefully monitored, as they can increase the risk of false-negative blocks when diagnosing cervical facet joint syndrome. In addition, intravascular injections can cause neurologic deficits such as spinal infarction or cerebral infarction. Digital subtraction angiography (DSA) is a radiological technique that can be used to clearly visualize the blood vessels from surrounding bones or dense soft tissues. The purpose of this study was to compare the rate of detection of intravascular injections during CMBBs using DSA and static images obtained through conventional fluoroscopy. METHODS: Seventy-two patients were included, and a total of 178 CMBBs were performed. The respective incidences of intravascular injections during CMBBs using DSA and static images from conventional fluoroscopy were measured. RESULTS: A total of 178 CMBBs were performed on 72 patients. All cases of intravascular injections evidenced by the static images were detected by the DSAs. The detection rate of intravascular injections was higher from DSA images than from static images (10.7% vs. 1.7%, P < 0.001). CONCLUSIONS: According to these findings, the use of DSA can improve the detection rate of intravascular injections during CMBBs. The use of DSA may therefore lead to an increase in the diagnostic and therapeutic value of CMBBs. In addition, it can decrease the incidence of potential side effects during CMBBs.

Survey on the treatment of postherpetic neuralgia in Korea; multicenter study of 1,414 patients.

BACKGROUND: Postherpetic neuralgia (PHN) is a serious complication resulting from herpes zoster infections, and it can impair the quality of life. In order to relieve pain from PHN, various treatments, including pharmacological and interventional methods have been used. However, little information on the recommendations for the interventional treatment of PHN, along with a lack of nation-wide surveys on the current status of PHN treatment exists. This multicenter study is the first survey on the treatment status of PHN in Korea. METHODS: Retrospective chart reviews were conducted on the entire patients who visited the pain clinics of 11 teaching hospitals from January to December of 2011. Co-morbid disease, affected site of PHN, routes to pain clinic visits, parenteral/topical medications for treatment, drugs used for nerve block, types and frequency of nerve blocks were investigated. RESULTS: A total of 1,414 patients' medical records were reviewed. The most commonly affected site was the thoracic area. The anticonvulsants and interlaminar epidural blocks were the most frequently used pharmacological and interventional methods for PHN treatment. For the interval of epidural block, intervals of 5 or more-weeks were the most popular. The proportion of PHN patients who get information from the mass media or the internet was only 0.8%.The incidence of suspected zoster sine herpete was only 0.1%. CONCLUSIONS: The treatment methods for PHN vary among hospitals. The establishment of treatment recommendation for PHN treatment is necessary. In addition, public relations activities are required in order to inform the patients of PHN treatments by pain clinicians.

Spinal cord stimulation in pain management: a review.

Spinal cord stimulation has become a widely used and efficient alternative for the management of refractory chronic pain that is unresponsive to conservative therapies. Technological improvements have been considerable and the current neuromodulation devices are both extremely sophisticated and reliable in obtaining good results for various clinical situations of chronic pain, such as failed back surgery syndrome, complex regional pain syndrome, ischemic and coronary artery disease. This technique is likely to possess a savings in costs compared with alternative therapy strategies despite its high initial cost. Spinal cord stimulation continues to be a valuable tool in the treatment of chronic disabling pain.

Treatment of idiopathic persistent hiccups with positive pressure ventilation -a case report-.

A 41-year-old male patient presented with idiopathic persistent hiccups. The hiccups did not respond to pharmacologic treatments including cisapride, omeprazole, and baclofen. Phrenic nerve block was also ineffective. However, the persistent hiccups were successfully treated with short-term positive pressure ventilation using a short-acting muscle relaxant.

Effect of dietary calcium on spinal bone fusion in an ovariectomized rat model.

OBJECTIVE: To evaluate the effect of calcium supplementation on spinal bone fusion in ovariectomized (OVX) rats. METHODS: Sixteen female Sprague Dawley rats underwent bilateral ovariectomy at 12 weeks of age to induce osteoporosis and were randomly assigned to two groups : control group (n=8) and calcium-supplemented group (OVX-Ca, n=8). Autologous spinal bone fusion surgery was performed on both groups 8 weeks later. After fusion surgery, the OVX-Ca group was supplemented with calcium in drinking water for 8 weeks. Blood was obtained 4 and 8 weeks after fusion surgery. Eight weeks after fusion surgery, the rats were euthanized and the L4-5 spine removed. Bone fusion status and fusion volume were evaluated by manual palpation and three-dimensional computed tomography. RESULTS: The mean fusion volume in the L4-5 spine was significantly greater in the OVX-Ca group (71.80±8.06 mm(3)) than in controls (35.34±8.24 mm(3)) (p<0.01). The level of osteocalcin, a bone formation marker, was higher in OVX-Ca rats than in controls 4 weeks (610.08±10.41 vs. 551.61±12.34 ng/mL) and 8 weeks (552.05±19.67 vs. 502.98±22.76 ng/mL) after fusion surgery (p<0.05). The level of C-terminal telopeptide fragment of type I collagen, a bone resorption marker, was significantly lower in OVX-Ca rats than in controls 4 weeks (77.07±12.57 vs. 101.75±7.20 ng/mL) and 8 weeks (69.58±2.45 vs. 77.15±4.10 ng/mL) after fusion surgery (p<0.05). A mechanical strength test showed that the L4-5 vertebrae in the OVX-Ca group withstood a 50% higher maximal load compared with the controls (p<0.01). CONCLUSION: Dietary calcium given to OVX rats after lumbar fusion surgery improved fusion volume and mechanical strength in an ovariectomized rat model.

Bispectral index monitoring as an adjunct to nurse-administered combined sedation during endoscopic retrograde cholangiopancreatography.

AIM: To determine whether bispectral index (BIS) monitoring is useful for propofol administration for deep sedation during endoscopic retrograde cholangiopancreatography (ERCP). METHODS: Fifty-nine consecutive patients with a variety of reasons for ERCP who underwent the procedure at least twice between 1 July 2010 and 30 November 2010. This was a randomized cross-over study, in which each patient underwent ERCP twice, once with BIS monitoring and once with control monitoring. Whether BIS monitoring was done during the first or second ERCP procedure was random. Patients were intermittently administered a mixed regimen including midazolam, pethidine, and propofol by trained nurses. The nurse used a routine practice to monitor sedation using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale or the BIS monitoring. The total amount of midazolam and propofol used and serious side effects were compared between the BIS and control groups. RESULTS: The mean total propofol dose administered was 53.1 ± 32.2 mg in the BIS group and 54.9 ± 30.8 mg in the control group (P = 0.673). The individual propofol dose received per minute during the ERCP procedure was 2.90 ± 1.83 mg/min in the BIS group and 3.44 ± 2.04 mg in the control group (P = 0.103). The median value of the MOAA/S score during the maintenance phase of sedation was comparable for the two groups. The mean BIS values throughout the procedure (from insertion to removal of the endoscope) were 76.5 ± 8.7 for all 59 patients in using the BIS monitor. No significant differences in the frequency of < 80% oxygen saturation, hypotension (< 80 mmHg), or bradycardia (< 50 beats/min) were observed between the two study groups. Four cases of poor cooperation occurred, in which the procedure should be stopped to add the propofol dose. After adding the propofol, the procedure could be conducted successfully (one case in the BIS group, three cases in the control group). The endoscopist rated patient sedation as excellent for all patients in both groups. All patients in both groups rated their level of satisfaction as high (no discomfort). During the post-procedural follow-up in the recovery area, no cases of clinically significant hypoxic episodes were recorded in either group. No other postoperative side effects related to sedation were observed in either group. CONCLUSION: BIS monitoring trend to slighlty reduce the mean propofol dose. Nurse-administered propofol sedation under the supervision of a gastroenterologist may be considered an alternative under anesthesiologist.