Sustained Pain Reduction Research Articles

Visual illusions modulate body perception disturbance and pain in Complex Regional Pain Syndrome: A randomized trial.

Effective treatment of longstanding Complex Regional Pain Syndrome (CRPS) is a challenge, as causal mechanisms remain elusive. People with CRPS frequently report distorted subjective perceptions of their affected limb. Evidence of pain reduction when the affected limb is visually altered in size suggests that visual illusions used to target central processing could restore coherence of this disrupted limb representation. We hypothesized that using virtual reality that alters hand image to match the patient's desired hand appearance would improve body perception disturbance and pain. Also, repeated exposure would maintain any therapeutic effect. A blinded randomized controlled trial of 45 participants with refractory upper-limb CRPS and body perception disturbance (BPD) viewed a digital image of their affected hand for 1min. The image was digitally altered according to the patient's description of how they desired their hand to look in the experimental group and unaltered in the control group. BPD and pain were measured pre- and post-intervention. A subgroup was followed up 2weeks after a course of repeated interventions. BPD (mean-6, ±SD 7.9, p=0.036, effect size [ES]=0.6) and pain intensity (mean-0.43, ±SD 1.3, p=0.047, ES=0.5) reduced in 23 participants after single exposure compared to controls (n=22). At follow-up, the subgroup (experimental n=21; control n=18) showed sustained pain reduction only (p=0.037, ±SD 1.9, ES=0.7), with an overall 1.2 decrease on an 11-point scale. Visually changing the CRPS hand to a desired appearance modulates BPD and pain suggesting therapeutic potential for those with refractory CRPS. Further research to optimize this therapeutic effect is required. Visual bodily illusions that change the shape and appearance of the painful CRPS hand to that desired by the patient result in a rapid amelioration of pain and body perception disturbance in people with longstanding CRPS. These findings highlight the future potential of this drug-free approach in the treatment of refractory CRPS.

Estrogen Regulation of the Expression of Pain Factor NGF in Rat Chondrocytes.

ObjectivePain is the main symptom of osteoarthritis (OA). Nerve growth factor (NGF) plays a crucial role in the generation of OA pain. And estrogen-alone used resulted in a sustained joint pain reduction in postmenopausal women. So we aim to find whether estrogen alters chondrocytes’ NGF level, affecting OA pain.MethodsPrimary chondrocytes and cartilage explants isolated from Sprague Dawley rat knees were cultured with physiological concentrations of estrogen (17β-Estradiol ≥ 98%, E2), Estrogen Receptor α (ERα) inhibitor and stimulants. Then, chondrocytes NGF mRNA expression and protein release were analyzed by a quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) respectively. Additionally, cultures were pre-incubated with MEK-ERK inhibitor to identify the signaling pathway that estrogen alters NGF mRNA and protein levels.ResultsWe found that chondrocytes NGF expression and release were decreased by E2. E2 also reduced chondrocytes IL-1β-stimulated or TGF-β1-stimulated NGF expression. Phosphorylated extracellular signal-regulated kinasep1/2 (p-ERK1/2) signals were detected stronger than the control group by Western Blotting (WB). When we cultured chondrocytes with PD98059 (MEK-ERK inhibitor, PD), NGF mRNA expression was added to 1.41Ct (2.07±0.1 fold).ConclusionWe showed that E2 reduces chondrocytes NGF expression significantly, even after stimulation by TGF-β1 or IL-1β. MEK-ERK signaling is involved in this process.

Endogenous anandamide and self-reported pain are significantly reduced after a 2-week multimodal treatment with and without radon therapy in patients with knee osteoarthritis: a pilot study

Multimodal therapies comprising spa applications are widely used as non-pharmaceutical treatment options for musculoskeletal diseases. The purpose of this randomized, controlled, open pilot study was to elucidate the involvement of the endocannabinoid system in a multimodal therapy approach. Twenty-five elderly patients with knee osteoarthritis (OA) received a 2-week spa therapy with or without combination of low-dose radon therapy in the Bad Gastein radon gallery. A 10-point numerical rating scale (pain in motion and at rest), WOMAC questionnaire, and the EuroQol-5D (EQ-5D) questionnaire were recorded at baseline, and during treatment period at weeks one and two, and at 3-month and 6-month follow-ups. Plasma levels of the endocannabinoid anandamide (AEA) were determined at baseline and at 2 weeks, and serum levels of several cartilage metabolism markers at all five time-points. A significant and sustained reduction of self-reported knee pain was observed in the study population, but no further significant effect of the additional radon therapy up and above base therapy. This pain reduction was accompanied by a significant reduction of AEA plasma levels during treatment in both groups. No significant differences were seen in serum marker concentrations between the groups treated with or without radon, but a small reduction of serum cartilage degradation markers was observed during treatment in both groups. This is the first study investigating AEA levels in the context of a non-pharmacological OA treatment. Since the endocannabinoid system represents a potential target for the development of new therapeutics, further studies will have to elucidate its involvement in OA pain.

Paget’s disease of bone: A clinical update

Paget's disease of bone (PDB) is a common destructive condition of bone that affects 1-2% of the population, most typically those over the age of 55 years. Itis usually asymptomatic. The aim of this article is to describe theclinical presentation, diagnosis and management of patients with PDB. Most cases of PDB are diagnosed incidentally on radiographs or as an isolated elevation of serum alkaline phosphatase. Symptomatic patients present with bone pain, fractures, arthritis and features of compression neuropathy. Diagnosis is made on the basis of typical radiological features on plain films, while a radionuclide bone scan may be used to assess the extent of disease. The mainstay of treatment for PDB is bisphosphonate therapy, with zoledronic acid being the most effective agent. Asingle infusion of zoledronic acid leads to a sustained reduction in bone pain and markers of bone turnover. However, bisphosphonates should be reserved for symptomatic patients, as treatment with these agents has been associated with an increase in rates of fracture in patients with asymptomatic PDB.

Denosumab in Patients With Fibrous Dysplasia Previously Treated With Bisphosphonates.

Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare bone disorder commonly treated with bisphosphonates, but clinical and biochemical responses may be incomplete. To evaluate the efficacy and tolerability of the receptor activator of nuclear factor-κB ligand inhibitor denosumab in the treatment of patients with FD/MAS refractory to bisphosphonate therapy. Case series. Academic center of expertise for rare bone diseases. Data were collected from 12 consecutive patients with FD/MAS with persistent pain and increased biochemical markers of bone turnover (BTMs) after long-term treatment with bisphosphonates (median, 8.8 years) and were treated with subcutaneous denosumab 60 mg at 3- or 6-month intervals with a follow-up for at least 12 months. Sustained reduction of BTMs and bone pain. A 60 mg dose of denosumab once every 3 months, but not once every 6 months, induced a sustained reduction of BTMs. After a median treatment period of 15.5 months (range, 12 to 19) serum alkaline phosphatase activity and propeptide of type 1 procollagen levels were respectively reduced from 212 ± 39.4 IU/L to 79 ± 6.0 IU/L (P = 0.004) and from 346.2 ± 111.1 ng/mL to 55.7 ± 16.6 ng/mL (P = 0.023) and normalized in 70% and 75% of patients, respectively. Although not quantitavely measured, 10 patients reported a reduction in bone pain of whom 6 reported complete elimination of pain. Treatment with denosumab was well tolerated. Our results indicate that 60 mg of denosumab every 3 months is a promising, well-tolerated treatment of most patients with FD/MAS refractory to bisphosphonate therapy. These results together with those of previously published case reports provide the necessary background for the design of a larger, controlled study.

HTX-011 reduced pain intensity and opioid consumption versus bupivacaine HCl in bunionectomy: phase III results from the randomized EPOCH 1 study

Background and objectivesThere is a need for local anesthetics that provide consistent analgesia through 72 hours after surgery. This study evaluates the use of HTX-011 (bupivacaine and meloxicam in Biochronomerpolymer...

Barefoot Running As A Treatment For Plantar Fasciitis In The Runner: A Case Series

PURPOSE: Plantar fasciitis is the most common running related injury associated with the foot and represents ~8% of all running injuries. The median recovery time for plantar fasciitis is ~5-months. Following the failure of conservative management for a female runner with plantar fasciitis, we trialled an alternate day treatment strategy of barefoot running on a grass surface (10 - 15 minutes). This approach was successful and was published as a medical case report. This abstract aims to describe the results of an emerging case series (n=4) using a similar approach. METHODS: Four amateur runners (2 male, 2 female, age 27-45 years) were diagnosed as having plantar fasciitis. In all cases, the failure of conservative management led to them being prescribed a barefoot running intervention on grass. Patients were instructed to complete 10-15 minutes (dependent on pain tolerance) of barefoot running every second day and record pain scores using the visual analog scale (VAS) every morning. RESULTS: Mean pain intensity (scored out of 10) at the beginning of the intervention was 5.4 ± 1.5 (range 3.5 - 7). After 6 sessions of barefoot running, mean pain intensity had reduced to 2.0 ± 1.6 (range 2.0 - 4.0). All patients demonstrated an improvement in pain intensity after 4-sessions. Three patients sustained this improvement up to session 6 and one patient reverted to their original pain score (4). The two female patients demonstrated an immediate and sustained reduction in pain. The two male patients initially remained unchanged or increased pain intensity before improving. DISCUSSION: The results of this emerging case series suggest that this intervention is at least well tolerated in runners with chronic plantar fasciitis. The fact that the intervention contains the activity known to worsen symptoms may suggest this approach has some promise. However, it is not possible to infer cause and effect from a case series and the improvements shown in this series may be due to other factors such as the passage of time or a reduction in fear avoidance behaviour.

Battlefield acupuncture for post-partum pain: A randomized controlled trial

Postpartum pain affects quality of life. Clinicians are increasingly using acupuncture for management of pain. Evidence based strategies that incorporate acupuncture for postpartum pain are lacking. We performed an exploratory, randomized clinical trial of Battlefield Auricular Acupuncture (BFA) plus standard analgesia versus standard analgesia alone for reduction of pain in the immediate postpartum period. The mean time to 50% sustained reduction of initial pain in the standard analgesia group (n = 33) was 6 days compared to 5 days in the standard analgesia plus BFA (n = 37) group (p = 0.35). The mean total morphine equivalent units (MEUs) in the standard group compared to standard plus BFA group were 88 mg and 82 mg respectively (p = 0.45). This exploratory comparison suggests that BFA may not provide additional benefit to standard analgesia for immediate postpartum pain; however, the trend toward faster reduction in pain indicates that a larger definitive study may be required.

Outcome of Stromal Vascular Fraction-Enriched Fat Grafting Compared to Intramuscular Transposition in Painful End-Neuromas of Superficial Radial Nerve: Preliminary Results.

The management of painful end-neuromas of the superficial branch of the radial nerve (SBRN) remains challenging due to high levels of pain relapse. The novel technique of stromal vascular fraction (SVF)-enriched fat grafting showed continuous pain relief, although failed to prove statistically significant. Besides acting as a mechanical barrier, SVF-enriched fat grafting might also affect the cellular level. The aim of this study was to compare clinical outcomes of SVF to the widely popular intramuscular transposition technique. In this cohort study, 10 consecutive patients treated for painful end-neuromas of the SBRN between 2010 and 2013 were analyzed retrospectively. Microsurgical resection of end-neuromas was performed in all patients. Five patients were treated with subsequent intramuscular transposition into the brachioradialis muscle and five patients received SVF-enriched fat grafting. Five different pain modalities and various predictors were compared pre- and up to 36 months post-operatively. In the transposition group, sustained pain reduction was not observed after an initial significant reduction 2 months' post-surgery, resulting in pain relapse at 36 months and comparable to the preoperative assessment. In the graft group, some degree of pain reduction was observed at 2 months after the surgery and proved to be constant in the long-term outcome, although not statistically significant compared to preoperative levels. Both SVF-enriched fat grafting and intramuscular transposition failed to prove statistical significant pain reduction in treating symptomatic neuromas of peripheral nerves.

Management of Sickle Cell Pain Using Pregabalin: A Pilot Study

Sickle cell disease (SCD) pain may have a neuropathic component. Adjuvant drugs used to treat neuropathic pain have not been studied for the treatment of adults with SCD. To determine the safety and feasibility of using pregabalin for chronic SCD pain. A randomized, controlled, double-blind pilot study. Based on random assignment, participants were treated with pregabalin or placebo control for 3 months with monthly follow-up visits. Participants were recruited from the University of Illinois Hospital and Health Sciences System outpatient SCD clinic. Participants/Subjects: A total of 22 participants with SCD (21 African American, 1 other) were included 16 women aged 18-82 (mean age 33.1 ± 9.9). PAINReportIt, Leeds Assessment of Neuropathic Signs and Symptoms, Neuropathic Pain Symptom Inventory, and Short Form 36 Health Survey were completed. Adverse effects were minimal. Mean scores for average pain intensity, composite pain index, and neuropathic pain revealed a reduction for pregabalin and placebo control groups. Although the between-group differences were not significant, sustained reduction in pain over time within the pregabalin group indicated promising effects of pregabalin for SCD pain. Mean quality-of-life scores increased slightly over time (representing better quality of life) in 7 of 8 domains for the pregabalin group and decreased in 4 of 8 domains for the placebo control group. Small sample size made it difficult to interpret quality-of-life findings. This pilot study provided sufficient evidence that further investigation of pregabalin's potential efficacy for treatment of chronic SCD pain in adults is warranted.

CT-guided cement sacroplasty (CSP) as pain therapy in non-dislocated insufficiency fractures

IntroductionIn elderly patients with reduced bone quality, insufficiency fractures of the sacrum are relatively common and are typically associated with severe disabling pain. The objective of the present study was to examine the feasibility of cement augmentation by CSP, to determine post-interventional leakages and other complications, and to present the outcome of pain over the course of 18 months.Materials and methodsIn 23 patients (20 women and 3 men) with an average age of 81.3 (71–92) years, a total of 41 sacral fractures were detected by MRI, 5 of them unilateral and 18 bilateral. Conservative treatment initially performed over a period of 3 weeks did not bring any satisfactory reduction in the severe disabling pain. The indication for intervention was established after an interdisciplinary case conference. The intervention was performed under intubation anaesthesia. Single-shot antibiotic prophylaxis was given routinely immediately prior to the intervention. Under sterile conditions, a Jamshidi needle was then advanced into the respective fracture zone in the sacrum from dorsal to ventral (short axis) or from lateral to medial transiliac (transiliac axis). After removing the inner needle, a flexible osteotome was inserted through the positioned hollow needle and used to extend the spongious space in the fracture zone and thus prepare a cavity for the cement filling. High-viscosity PMMA cement was then inserted discontinuously with the aid of a pressure gauge under low-dose CT control. Cement leakages were determined in the CT image on the day after the intervention, all cement outside of the cortical boundary being rated as a leakage. Pain was documented on a visual analogue scale (VAS) on the day before the intervention, on the second day, and 6, 12, and 18 months after the intervention. Additionally occurring complications were recorded, and the patients were asked to rate their satisfaction after 6 and 18 months.ResultsCSP was technically feasible in all patients. In the control CT scan, sufficient cement distribution and interlocking with vital bone were found along the course of the fracture in the sacrum. An average of 6.0 ± 0.83 ml of cement was inserted per fracture. Leakage was found in 5 of 41 (12.2%) of the fractures treated, although none were symptomatic. The mean pain score on the VAS was 8.8 ± 0.59 before the intervention, a significant pain reduction (p < 0.0005) was seen on the second post-operative day, with an average value of 2.1 ± 0.36, and this was stable at 2.2 ± 0.28 after 6, 2.3 ± 0.31 after 12, and 2.2 ± 0.41 after 18 months. Now that they no longer experienced disabling pain, all of the patients were fully remobilised and discharged back home. A high level of patient satisfaction was found after 6 and 18 months.ConclusionAs a minimally invasive procedure, CSP is an effective treatment method for rapid, significant, and sustained pain reduction.

Case Report: Scrambler Therapy for the Treatment of Chronic Post-Mastectomy Pain (cPMP)

Chronic post-mastectomy pain (cPMP), including post-lumpectomy pain, is common with no established ways of treatment. We treated three consecutive patients referred with cPMP with scrambler therapy (ST), a non-invasive electrical neurocutaneous stimulation. Treatment was given across the area of pain following the dermatomes for 45 minutes daily, for several consecutive days until relief, and then was repeated as needed. The ST MC5A device synthesizes 16 different waveforms that resemble action potentials, delivered to the surface receptors of the c-fibers, to send “non-pain” information along the damaged pathways to reduce central sensitization. All three had marked (over 75%) and sustained (months) reduction of allodynia, hyperalgesia, and pain. All reported marked improvements in their quality of life and normal function. One woman was able to stop chronic opioid use. No side effects were observed.Scrambler therapy is a promising way to relieve cancer and other types of neuropathic pain, and may be helpful in cPMP. Further prospective trials are warranted.

Long-term therapeutic effects of dextrose prolotherapy in patients with hypermobility of the temporomandibular joint: a single-arm study with 1-4 years’ follow up

The aim was to analyse the short-term and long-term therapeutic efficacy of dextrose prolotherapy for dislocation or subluxation (hypermobility) of the temporomandibular joint (TMJ). Sixty-one patients with symptomatic hypermobility of the TMJ were included in this single-arm prospective study, in which they were each given four sessions of intra-articular and pericapsular injections six weeks apart. Each injection comprised 10% dextrose/mepivacaine solution 3ml. Clinical outcomes including severity of pain on movement according to the numerical rating scale (NRS), maximal interincisal opening, clicking, and frequency of locking were measured before treatment (T1), during treatment (T2) (just before the third session of injections), at the short-term follow-up (T3) (three months after treatment), and at the long-term follow-up (T4) (1-4 years after treatment). Condylar translation and osseous changes of each joint were evaluated at T1 and T4 using tomography. There was significant reduction in all variables by T2 (p<0.001, p<0.001, p=0.006, and p<0.001). The pain scores (p<0.001) and clicking (p<0.001) had decreased significantly by T3. Linear tomograms of each joint at T1 and T4 showed no alteration in the morphology of the bony components of the joint, and at T4, tomographic open views of all joints showed condylar hypertranslation. Dextrose prolotherapy provided significant and sustained reduction of pain and recovery of constitutional symptoms associated with symptomatic hypermobility of the TMJ without changing either the position of the condyle or the morphology of the bony components of the joint.

Diode Laser Cyclophotocoagulation in the Management of Pain and Intraocular Pressure Control in Patients with Terminal Glaucoma—Six Years’ Experience

Objective: This study aims to describe the experience with diode laser cyclophotocoagulation in the control of intraocular pressure and resolution of pain in patients with refractory glaucoma. Methods: Retrospective study. 64 eyes of 60 patients who underwent cyclophotocoagulation between January 2008 and March 2014. Evaluation of the pre- and post-operative intraocular pressure, the control of ocular pain, the number of anti-glaucoma drugs used in pre- and post-intervention, the rate of complications and the success rate. Results: There was an overall success rate of 81.3%, with 9 eyes needing a second intervention. There was a mean reduction of 52.6% of the preoperative mean intraocular pressure of 41.25 to 19.56 mmHg at 12 months observation (p < 0.001). There was also a statistically significant reduction in the number of anti-glaucoma drugs used from 3.19 to 2.01 per eye and the resolution of pain in 75% of patients. Conclusions: cyclophotocoagulation is an effective procedure, with an expected positive impact on quality of life of patients as a result from the decreased number of anti-glaucoma drugs, sustained intraocular pressure reduction and resolution of pain.

Pain Outcomes in Patients Undergoing CT-Guided Celiac Plexus Neurolysis for Intractable Abdominal Visceral Pain.

The purpose of this study was to assess outcomes in patients who have undergone celiac plexus neurolysis (CPN) as treatment for refractory abdominal visceral pain at a tertiary care medical center. This study involved retrospective analysis of all patients who had undergone computed tomography (CT)-guided CPN over a 7-year period, as identified in the medical record. Cases were categorized into 1 of 3 groups-group 1: patients getting at least moderate improvement in pain but with improvements subsiding within 2 days; group 2: patients with some sustained pain relief but still requiring heavy doses of narcotics; group 3: patients with major or complete sustained reduction in pain where the narcotic dose was able to be reduced. One hundred thirty-eight cases were identified, 51 of which had no or insufficient follow-up, leaving 87 cases for analysis. Of the 87 cases, 31 (36%) were categorized as group 1, 21 (24%) as group 2, and 35 (40%) as group 3. There were no statistical differences in outcomes based on patient age, gender, time since diagnosis, or type of cancer. Documented postoperative complications were diarrhea (11 cases) and 1 case each of obtundation, hypotension, and presyncopal event. We conclude that patients undergoing CT-guided CPN for abdominal visceral pain achieve moderate or major short-term pain relief in a majority of cases. The procedure is safe with minimal complications.

(416) Intrathecally injected bone marrow stromal cells produce sustained neuropathic pain reduction in paclitaxel-treated mice

Chemotherapy-induced peripheral neuropathy is the de facto toxic effect that limits the administration of anti-neoplastic agents such as paclitaxel in the treatment of cancer. This toxic effect limits the utilization of aggressive chemotherapeutic regimens associated with an increase in patient survival from cancer. Thus, it is urgent to develop new treatments to prevent and reverse chemotherapy-induced neuropathic pain. Recently, we discovered that intrathecal injection of bone marrow stromal cells (BMSCs) reduced peripheral neuropathy for more than two months in two mouse models of neuropathic pain induced by chronic constriction injury and spared nerve injury. We also found that TGF-b1 was the factor secreted by BMSCs responsible for the reduction in neuropathic pain, and furthermore the intrathecally injected BMSCs migrated specifically to the border of injured dorsal root ganglia (DRGs) through an interaction between CXCL12 and CXCR4. In this study, we examined the effects of BMSC intrathecal injection on chemotherapy-induced peripheral neuropathy in the murine paclitaxel model (4 intraperitoneal injections on alternate days (day 1, 3, 5, and 7), 2.0 mg/kg). We found that a dosage of 3.0 x 105 cells (10 ul, BMSCs) injected in the intrathecal space of paclitaxel-treated mice produced a significant reduction in mechanical allodynia that lasted for more than six weeks. We also confirmed that TGF-b1 injected intrathecally at a dosage of 100 ng produced a transient reversal of mechanical allodynia in paclitaxel-treated mice. These findings suggest BMSCs injected into the intrathecal space and their secreted factors such as TGF-b1 can reduce neuropathic pain associated with chemotherapy-induced peripheral neuropathy. We are currently searching for other beneficial factors from stem cells that can reduce neuropathic pain, control neuroinflammation, and protect neurons from nerve injury. (Chen et al., J Clin. Invest, 2015, 125:3226-40.) Supported by NIH R01 grants NS67686, NS87988, DE17794, and DE22743.

Non-invasive magnetic resonance-guided high intensity focused ultrasound ablation of a vascular malformation in the lower extremity: a case report.

IntroductionTherapy of choice for symptomatic vascular malformations consists of surgery, sclerotherapy, or embolization. However, these techniques are invasive with possible complications and require hospitalization. We present a novel non-invasive technique, i.e., magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation, for the treatment of a vascular malformation in a patient. This technique applies high-intensity sound waves transcutaneously to the body and is fully non-invasive. MRI guidance is the novel aspect of HIFU treatments and is used for exquisite delineation and localization of the lesion and accurate real-time temperature monitoring during tissue ablation. MR-HIFU is a well-established treatment option for uterine fibroids and is currently being investigated for, e.g., bone tumors, breast cancer, prostate cancer, and liver cancer. MR-HIFU of vascular malformations has not been a topic of research yet.Case descriptionVolumetric MR-HIFU ablation of a vascular malformation in the lower extremity of an 18-year-old male patient was performed. Temperatures of 62–80 °C were reached in the target lesion with sonications of 4 × 4 × 8 mm using powers of 200 W for <20 s. At 1-month follow-up, the patient reported qualitatively sustained reduction of pain and normal motor function. Three-month follow-up imaging indicated successful nidus destruction, which resulted in reduction of >30 % of the tumor volume. After 13 months, pain score was reduced to <2 after extreme exertion for several hours and to 0 for daily activities.Discussion and evaluationRadiofrequency ablation and cryoablation are minimally invasive techniques that have been tried on low-flow vascular malformations with inconsistent results. Furthermore, both techniques require probe insertion, which is associated with risks of wound infection and hospitalization. Since MR-HIFU is truly non-invasive, these risks are negligible.ConclusionsIn conclusion, we reported a successful non-invasive treatment of a vascular malformation with MR-HIFU in a clinical patient including long-term follow-up data for the first time. The patient reported qualitatively sustained pain reduction up to 13 months post treatment.

Intra-articular augmentation of lubrication with silk microspheres

Purpose: Osteoarthritis of the knee represents a large unmet clinical need. Deficits in synovial lubrication have been reported in osteoarthritis, and several strategies to augment lubrication have shown preclinical benefit. We hypothesized that augmentation of the boundary lubrication of synovial fluid by intra-articular administration of long-residence non-inflammatory lubricating silk microspheres could reduce mechanical injury and pain in an osteoarthritis animal model. Methods: Silk microspheres with phospholipid coatings were prepared by a modified version of previously published methods. Osteoarthritis was induced in rats using the surgical instability model consisting of MCL tear and meniscectomy. One week following injury, affected knees were intra-articularly administered saline vehicle or silk microspheres (2.5mg). Serial body weights, knee effusion, gait analysis on Day 14, and Von Frey secondary allodynia testing on Days -1, 6, and 13 were measured. Severity of osteoarthritis was assessed by histopathologic analysis by a trained pathologist on Day 28 after injury. Results: Silk microspheres with varying size distributions were synthesized and achieved coefficients of friction approaching 0.05 to 0.02. Intra-articular injection of silk microspheres was well tolerated in rats with no adverse reactions. Von Frey testing of secondary allodynia 6 days after injection indicated a trend towards a modest but sustained reduction of osteoarthritic pain. Conclusions: Intra-articular silk microspheres offer a novel, biologically inert, non-inflammatory, and well tolerated potential therapy for osteoarthritis. These results motivate further formulation optimization of silk microsphere composition to tune synovial residence, degradation profile, lubrication properties, and potentially to provide prolonged delivery of active therapeutics. Augmentation of joint lubrication with silk microspheres merits further preclinical exploration as a novel therapy to address the unmet need in osteoarthritis.

5:36 PM, Abstract No. 93 - Pain outcomes in patients undergoing CT-guided celiac plexus neurolysis

To assess outcomes in patients who have undergone celiac plexus neurolysis (CPN) as treatment for malignant abdominal visceral pain at a tertiary care medical center. There is limited data on CPN outcomes using modern techniques with CT guidance. All patients who had undergone CT-guided CPN over a 7-year period were identified using the Montage data and analytics system. The electronic medical record for each case was thoroughly examined and consolidated into a case summary. All statements related to the patient’s visceral pain and CPN procedure (including from clinicians, patients, and/or discharge summaries) were considered relevant for incorporation into the case summary. Cases were then categorized into one of 3 groups. Group 1: No relief or temporary but unsustained relief (defined as patients getting at least moderate improvement in pain, but with improvements subsiding within 2 days); Group 2: Moderate relief (patient with some sustained pain relief but still requiring heavy doses of narcotics); Group 3: Major relief (patient with major or complete sustained reduction in pain and significant reduction in narcotic burden); Complications potentially related to the CPN were also documented. 138 cases were identified, 51 of which had no or insufficient follow-up, leaving 87 cases for analysis. This included 49 inpatient cases and 38 outpatient cases. Of the 87 cases, 31 (36%) were categorized as Group 1, 21 (24%) as Group 2, and 35 (40%) as Group 3. There were no statistical differences in outcomes based on patient age, gender, time since diagnosis, or type of cancer. Documented post-operative complications were diarrhea (11 cases) and one case each of obtundation, hypotension, and pre-syncopal event. Patients undergoing CT-guided CPN for abdominal visceral pain achieve moderate or major short-term pain relief in a majority of cases. The procedure is safe with minimal complications.

Patient Experience Following Kyphoplasty: Safety, Efficacy, and Patient Satisfaction

Aims: Kyphoplasty is a minimally invasive treatment used to reduce pain, restore vertebral height and improve mobility in patients with painful spinal VCF. Pain from vertebral compression fractures (VCF) comprises an important health issue with significant social and economic impact, particularly in elderly patients with osteoporosis where treatment options are limited. We assessed outcomes Original Research Article Kicielinski et al.; BJMMR, 10(1): 1-11, 2015; Article no.BJMMR.19370 2 in patients with VCF who failed conservative management and underwent kyphoplasty. Study Design: Prospective and retrospective case series. Place and Duration of Study: At a single neurosurgical practice February 2003 and September 2012. Methodology: A total of 203 patients with 288 treated vertebral body fractures treated with kyphoplasty were enrolled. The Visual Analog Scale (VAS) was used to prospectively measure back pain before and after surgery. Pre and post operative disability and quality of life were retrospectively measured with the Roland Morris Disability Index (RMDI) and EuroQol 5-Domain scale (EQ5D), respectively, via patient survey. Pre and post-operative narcotic analgesic usage and incidence of subsequent fractures were recorded. Results: There was a statistically significant improvement (P < .001) in each of the assessed measures following surgery. The post-operative rate of narcotic use was reduced from 63% to 17%. Eight patients (4.2%) developed and underwent repair of an adjacent fracture with a mean time between surgeries of 461 days. Conclusion: Following kyphoplasty, patients experienced significant, rapid, and sustained reduction of back pain, improved quality of life, and reduced disability with a low complication rate. Timely repair of VCF is indicated, not only to prevent complications associated with prolonged inactivity but also for effective treatment of severe pain in the acute setting.