Background and aims:
With our ageing population, the number of elderly people undergoing surgical procedures is increasing. The incidence and intensity of postoperative pain in elderly patients is poorly described. This study aims to examine the influence of ageing on postoperative pain, administering opioids and wish for treatment.
Methods: 
After ethical approval and receiving informed consent, international data of surgical patients undergoing spine surgery, total hip replacement, total knee replacement or laparoscopic cholecystectomy were collected between 2010 and 2018 as part of the PAIN OUT program, an international European Union-funded registry. Pain was measured on postoperative day 1 (POD1) using the Numeric Rating Scale (NRS) from 0 – 10. We performed a linear regression or binary logistic analysis for continuous or dichotomous outcomes, respectively.
Results: 
A total of 11.971 patients underwent one of the afore mentioned types of surgery. The reported maximum pain levels decreased significantly with age (β = -0.008, p<0.001). The age related decrease in pain scores was more pronounced in women compared to men (Figure1). The number of times of administering opioids on the ward decreased significantly with ageing (β = -0.012, p<0.001) and the wish for more treatment decreased also with ageing (β = -0.008, p<0.001).
Conclusions: 
Maximum pain scores on POD1 decrease with increasing age in both men and women. Older patients were administered less often opioids and had less often a wish for more pain treatment than younger patients.

INFLUENCE OF AGING ON POSTOPERATIVE PAIN: RESULTS FROM THE INTERNATIONAL PAIN OUT REGISTRY

Background
Humans deal frequently with changes in path direction (Segal et al. 2008), yet few studies evaluate gait along curved trajectories. Given the importance of neck sensorimotor control during walking and turning [1], it is clinically relevant to consider the impact of the neck pain which may can impair the muscular ability to absorbing the ground reaction forces propagating from the legs to the head during gait [2] and can altered the coactivation to avoid the pain [3].


Aims
This study examined the shock attenuation function at neck, trunk and leg level and the time-varying multi-muscle coactivation function on different muscles at neck and back level during walking along rectilinear and curvilinear trajectories in people with chronic neck pain (CNP) versus asymptomatic control (AC). 

Methods
Twenty-six AC (age: 26±10.6 years) and twenty-one subjects with CNP (age: 28.5±12.4 years, average pain intensity: 4.5±1.9/10) performed three gait repetitions at natural speed, along a rectilinear path (10m) and a curvilinear path clockwise and counterclockwise (1m radius) and simultaneously,  a motion analysis system was used for the acquisition of  kinematics and muscle activity. 

During the gait subjects wore six passive reflective positioned above the anatomical reference points and a system of acquisition sEMG (FreeEMG, BTS SpA, Milan, Italy) with probes places on splenius capitis sternocleidomastoid and erector spinae right and left side muscles.

From the processed EMG signals, we calculate the simultaneous activation of the muscles using the time-varying multi-muscle coactivation function (TMCf) proposed by Ranavolo [4]. Mean shock attenuation index (MSA) at neck, trunk and leg was calculated from the power spectral density of the respective segments during the right gait cycle [5]. The MSA and TMCf were compared between groups by using parametric tests (two-tailed) and repeated measure analysis of variance (ANOVA) according to the data distribution.

Results
The mean MSA at the neck level  was significantly higher (less shock absorption) in CNP compared to AC during external direction (P=0.020, see Figure 1) and the TMCf in the sternocleidomastoid was significantly higher in CNP during the same direction (P=0.021, see Figure 2) as well, while no significant differences were found for the other gait directions for MSA indexes or TMCf mean.

Conclusion
The reduced shock absorption at the neck level in people with CNP can be due to impaired control of the neck muscles. The higher speed of the outer (external to the curvilinear direction) part of the body motivates the higher MSA neck for CNP during the counterclockwise condition (outer right gait cycle). Challenging the motor control, with curvilinear gait, highlights impairments in the shock absorbing function and in the coactivation of the neck in people with CNP.

IMPAIRED SHOCK ATTENUATION IN PEOPLE WITH CHRONIC NECK PAIN DURING CURVILINEAR GAIT

Background
The surgery of knee arthroplasty produces intense postoperative pain and its management is still a challenge.
The aim of the study is to evaluate the analgesic efficacy and safety of sublingual sufentanil in the postoperative of total knee arthroplasty.

Methods
The study prospectively compares a group of patients who underwent knee replacement and received postoperative femoral block and sublingual sufentanil by Zalviso system (n = 31) versus a historical cohort of patients (n = 33) operated of knee arthroplasty who have received double block femoral + sciatic and rescues of subcutaneous methadone.

Results
Patients of both groups are comparable in age, comorbidities and type of surgery.
In both groups of patients, the mean VAS corresponded to controlled pain.
In the Zalviso group we found 8 patients with adverse effects (25%). Nausea and vomiting in 1 (3.2%). Dizziness in 3 (9.6%). Constipation in 3 (9.6%). Insufficient analgesia in 1 (3.2%) Disorientation in 2 (6.45%)
In the control group, 8 patients (24%) presented adverse effects. Pain in 2 (6%). Constipation in 3 (9%). Intolerance to methadone 1 (3%) and disorientation in 2 (6%)
Regarding the hospital stay, the difference has not been statistically significant.
The patients at the end of their hospital stay evaluated the satisfaction with the analgesic technique used on a scale of 1 to 10. The Zalviso group obtained the score (8.61 vs. 6.82, p = 0.000).
Conclusion:
 Sublingual sufentanil in Zalviso device is an option for pain control in the postoperative period of total knee arthroplasty

SUBLINGUAL SUFENTANIL IN ZALVISO SYSTEM FOR KNEE ARTHROPLASTY IN OUR EXPERIENCE. PRELIMINARY RESULTS

Background & Aims: A systematic review of 23 population-based studies has revealed a range of risk factors for the onset of fibromyalgia (FM) and chronic widespread pain. This study aimed to identify which variables, out of many, predict new onset FM in a large population-based sample and compare them with the predictors of new onset irritable bowel syndrome (IBS) and chronic fatigue syndrome (CFS).

Methods: The Dutch prospective, population-based Lifelines study screened 152,180 participants at baseline using many physical, psychological and social variables. After excluding participants with pre-existing disorders, we identified new onsets of FM, IBS & CFS over the subsequent 3 years. We assessed the baseline predictors of each disorder using penalised logistic regression .

Results: New onset FM was reported by 692 participants (90% were female);  1,595  reported new IBS (75% female) and  296 CFS (52.7% female).  There were 19 predictors of FM, 9 of these also predicted IBS and/or CFS, including female sex, gastro-intestinal disorders, sleep disturbance, chronic health difficulties, somatization, negative health perception. Predictors unique to FM included: IBS and musculoskeletal disorders at baseline, taking medication for upper gastrointestinal disorders, thyroid and ophthalmic disorders, no recent GP contacts, raised BMI and low alcohol consumption.   

Conclusions: The predictors of new onset self-reported FM in this study concurred mostly with previously reports. It is unlikely that they relate to a single path into FM, rather there may be several paths, some are common to other syndromes and some are unique to FM.

THE RISK FACTORS FOR NEW ONSETS OF FIBROMYALGIA: THE LIFELINES STUDY

Back-UP is an IT system that is being developed to support a personalised management of nonspecific neck and low back pain, using digital clinical data, prognostic models and knowledge of evidence-based treatments.
The data processed by the platform comprises multiple health dimensions, from the smallest scale (glycomics), through biomechanics, to psychosocial factors assessed by validated questionnaires and psychological tests. The knowledge-based system will estimate the most likely future outcomes, quantified by standard pain and disability scales (e.g. RMDQ for low back pain and NDI for neck pain), measures of time off work, and probability of recurrence. It will also provide information about matched treatments, costs, adaptation to the workplace, or insurance-related issues.
The system is addressed to three broad types of users: the professionals that treat the patient, the patients themselves, and researchers. Back-UP’s infrastructure comprises three platforms specifically oriented to those users, which with each other through APIs that facilitate the exchange and re-use of information through the trajectory of a patient, in the recovery and return-to work process.

CLINICAL MANAGEMENT OF NECK AND LOW BACK PAIN THROUGH PERSONALISED PROGNOSTIC MODELS: THE BACK-UP PROJECT

Background and aims: Painful diabetic neuropathy (PDN) is a complex complication associated with poor glycaemic control. Current treatments for PDN aim to treat the symptoms of pain and discomfort and are mainly pharmacological but have limited effectiveness. However, less is known about alternatives such as psychological treatments and the role of psychological variables related to PDN. The aim of this study is to survey people with PDN and examine the role of psychological flexibility (PF) in relation to their daily functioning. 

Methods: This is a questionnaire-based, cross-sectional study with 225 participants (mean age 52.05 + 12.06), who were recruited from NHS and online.

Results: In correlation analyses, acceptance of pain was shown to be negatively correlated to pain intensity (r=-0.21, p<0.01), pain distress (r=-0.25, p<0.01) functional impairment (r=-0.38, p<0.01), depression severity, (r=-0.41, p<0.01), and depression impact (r=-0.41, p<0.01). Committed action also correlated negatively with functional impairment (r=-0.22, p<0.01), depression severity (r=-0.43, p<0.01) and depression impact (r=-0.21, p<0.01). Results from regression analyses show that the combination of four variables representing psychological flexibility accounted for significant variance in most equations. In the equation for depression severity, pain intensity accounted for 23.3% of variance. In the equation for depression impact, pain intensity accounted for 13.2% of variance.

Conclusions: These results highlight the potential utility of PF in the design and implementation of psychological interventions for individuals from PDN. The reliability and generalisability of the results need to be established.

A STUDY OF THE ROLE OF PSYCHOLOGICAL FLEXIBILITY AMONG UK ADULT PATIENTS WITH PAINFUL DIABETIC NEUROPATHY

Abstract 
Objective: to evaluate the functional disability associated to the impact on the quality of life of patients with knee osteoarthrosis (OA), followed by educational actions for self management. Method: A cross-sectional, descriptive and analytical study with a sample of 32 patients 50 years old with knee OA and radiographic findings of Kellgren and Lawrence grade II or higher who may be receiving oral or topical analgesics. Pain and function were assessed by Brief Inventory of Pain and WOMAC. Quality of life (QOL) was used by Whoqol-bref and the emotional aspects were verified by the Hospital Anxiety and Depression Scale. Results: The mean age was 61 ± 5.8 years, 62% female, with a mean duration of knee OA of 5.4 ± 2.5 years. The degrees of KL were: grade 2: 21/32 (65.6%); grade 3: 8/32 (25%); grade 4: 3/32 (9.4%). Subjects had a mean educational level of 8.5 ± 3.5 years. After applying a short-term program with participatory education and self-management strategies, there was a telephone reinforcement after 1 month and reassessment after 3 months, where the intensity of pain and walking, sleep, work and the use of the life were significantly better (p ≤ 0.05). The positive impact on QoL was in the physical, psychological and environmental domains and, when correlating QoL and functional disability, a significant result was observed in the physical aspects (r = 0.40 ). Conclusion: Educational actions for self-management, strengthened by guidelines and telephone reinforcements, proved to be effective in patients with knee OA.

MANAGEMENT THE FUNCTIONAL STATUS AND THE QUALITY OF LIFE OF PATIENTS WITH KNEE OSTEOARTROSIS AND RELATED FACTORS

Background and Aims:
Pulsed radiofrequency is the application of a high-frequency current with microseconds pause. This modality is a non-invasive one and it does not produce pain.
Methods:
We describe 3 cases of knee pain in elderly patients where the Surgery had been dismissed. We measured the efficacy in reducing the pain and how long did it last.
Results
2 of them experienced a reduction of more than 90 % of the pain. The other one only experienced an improvement of 50 % of the pain. The pain improvement lasted mínimum three months with the option to repeat this therapy.
Conclusions: Transcutaneous pulsed radiofrequency can be a non-invasive treatment for the painful knee with a high effectivity. More research might be conducted.

TRANSCUTANEOUS PULSED RADIOFREQUENCY TREATMENT IN PATIENTS WITH PAINFULL KNEE

The sense of presence induced by the immersive environment of virtual reality, coupled with the precise sensory control, signify a potentially effective new tool for the management of pain. While several lines of research focusing on virtual reality have evinced successful analgesia through momentary distraction, others have utilized embodiment paradigms to examine how experimental alteration of the bodily self in virtual reality can minimize pain perception. Successful analgesia has ensued from modification of physical attributes for both experimental and chronic pain, suggesting that the sense of embodiment could play a significant modulatory role in the management of pain. Recently, a novel study demonstrated that the application of a sham analgesic cream to an embodied rubber hand, even when not applied to the physical hand, can successfully induce placebo analgesia.
The current study bridges the domains of placebo analgesia and virtual embodiment to examine whether a virtual placebo can successfully induce analgesia, and whether the magnitude of analgesia experienced from a virtual placebo differs from that of a placebo administered in physical reality. Participants (n=40) were assigned to either a Placebo or Control group and completed all experimental procedures in virtual (VR), augmented (AR), and physical reality (PR). Placebo participants (n=20) were informed that the efficacy of a physical, heat protective glove in physical reality would be compared to the analgesic efficacy of its purely virtual counterparts in virtual and augmented reality, whereas Control participants (n=20) were only told that the glove served to conduct the experiment under different visual conditions. Participants received noxious thermal stimulations to the right lower forearm while pain threshold, sensory pain (i.e., how painful was the stimulation) and subjective pain (i.e., how unpleasant was the stimulation) were measured. Results from the mixed ANOVA evince that participants in the Placebo condition, after the intervention, exhibited significantly higher pain thresholds (F(1,114) = 65.03, p < .001), lower sensory pain ratings (F(1,114) = 14.39, p <.001), as well as lower subjective pain ratings (F(1,114) = 9.57, p < .01) than Control participants, independent of the reality used.
Our results further inform the growing field of virtual therapy by elucidating that top-down cognitive mechanisms experienced during placebo analgesia are just as successful when the placebo is virtual (AR), or even when both the placebo and the body are completely virtual (VR). With therapeutic virtual reality on the rise as a potentially indispensable tool for clinical healthcare, our findings could complement other sensory manipulations in virtual reality, such as targeting the physical attributes of the virtual avatar, for pain management.

01 - PLACEBO ANALGESIA IN VIRTUAL AND AUGMENTED REALITY

Background and aims
To estimate the prevalence of chronic low back pain (CLBP) in the general adult Spanish population and to establish CLBP patient groups according to the health status, mental health, pain level and its impact.
Methods
Data has been obtained from the National Health Survey of Spain 2017 with a sample of 23089 adults. Based on the health status, mental health (GHQ-12), pain level and its impact on daily activities, a cluster analysis was performed to identify groups of CLBP patients. Chi-squared and Kruskal-Wallis-H tests were used to analyze differences between groups.  
Results
The prevalence of CLBP was 22% (CI95%:21.5-22.5), and 63.8% were women with a mean of 62.08 years old.
Three groups of CLBP patients were identified. Group 1 (N=766), worse group, including   subjects with bad/very bad health status (85.6%), a higher score in GHQ-12 (Mean=8.57), with severe/extreme pain (61.7%) and quite/a lot of impact of pain on daily activities (72.3%). Group 2 (N=2141), medium group, with subjects referring regular health status (56.3%), a score of 2.11 in GHQ-12, with moderate/mild pain (61.6%) and a moderate impact of pain on daily activities (48.4%). Group 3 (N=2170), better group, including subjects with good/very good health status (60.6%), a lower score in GHQ-12 (Mean=0.89), without pain or very mild/mild (84.1%) and without or little impact of pain on daily activities (99.4%). 
Conclusions
There is a high prevalence of CLBP in Spain, with differences in the characteristics of the patients. Identifying groups of patients could serve to personalise therapeutic strategies.

CHRONIC LOW BACK PAIN IN THE ADULT'S SPANISH POPULATION: IDENTIFYING CLINICAL SUBGROUPS THROUGH CLUSTER ANALYSIS

Background and aims
To estimate the prevalence of pure central (CNP) and peripheral neuropathic pain (PNP) among patients attending pain clinics in Spain. To analyse factors associated with pain intensity and QoL.
Methods
Cross-sectional study involving most of the pain clinics in Spain was carried out, 53 patients with pure CNP and 281 with pure PNP were included. Pain specialists used the revised grading system proposed in 2008 to decide definite, probable or possible diagnostic of NP. 
Results
The prevalence of CNP was 2.4% (CI95%:1.7;3.1) and 12.9% (CI95%:1.5;14.3) of PNP patients. Both group of patients had a high frequency of co-morbid anxiety, depression or sleep disorders, being higher in CNP patients (51.1 %, 71.4%, 71.4%, respectively).
Definite CNP was more likely in patients with lower limbs pain location. In PNP patients, definite diagnostic was more frequent in upper limbs pain location. 
Pain intensity in PNP patients was associated with the presence of depression and sleep disturbances, however, in CNP patients, was related to lower limbs pain location. 
The impairment of QoL was greater in CNP patients than PNP patients, being pain location, presence of depression and sleep disturbance the factors most negatively affecting QoL. Among PNP patients, women and those with higher pain intensity had worse QoL, however, older age and diagnostic certainty were positively related to QoL.
Conclusions
Pain intensity and QoL are affected by different factors in patients suffering central or peripheral neuropathic pain. Identifying these factors could serve to guide therapeutic strategies and improve QoL of patients.

PREVALENCE OF CENTRAL AND PERIPHERAL NEUROPATHIC PAIN AND IMPACT OF DEPRESSION, ANXIETY AND SLEEP DISORDERS ON THE INTENSITY OF PAIN AND QUALITY OF LIFE

Introduction
Chronic low back pain (CLBP) that lasts for more than six month is estimated to occur in 60-80% of the general population in their lifetime and is associated with substantial healthcare costs. In this study, we utilized endoscopy for the precise microsurgical and ablation (ESIJ) of the potential pain generators associated with the SIJ and evaluated the clinical efficacy of this new technique.
Material and Methods:  
The medical records of 30 consecutive patients who underwent ESIJ for SIJ arthropathy and pain in CLBP between January 2016 and February 2018 were reviewed.

In order to confirm the SIJ pain as the main source of CLBP, three separate intraarticular SIJ and medial branch blocks of the lower facet joints (L4-S1) were performed under C-arm
control at least 3 weeks before the ESIJ-procedure. If patient experienced 50% or higher improvement less than two weeks in pain from baseline according to visual analogue scale (VAS) after this block, SIJ complex was considered to be the main pain generator, and ESIJ was scheduled.
Results:  
More than 350 endoscopic procedures of SIJ (ESIJ) were performed from January 2016 till February 2018.30 patients with SIG arthropathy in CLBP over 6 month were included by precise criteria (s.e.). At baseline the VAS was 7,23, ODI 44,8 and age of 56 (11 male, 19 female). After the ESIJ procedure the patient had an significant improvement in pain relief (measured by VAS) and functional ability (measured by ODI) at 3 to 24 months: VAS reduction from 7,23 baseline to 1,72 / 2,82 after 21/24 month significantly by 80% pain relief ODI ability improvement from 44,8 baseline to 22.2 significantly in lumbar function.
Conclusion:  
This new easy to perform endoscopic electrothermic procedure of the SIJ (ESIJ) shows good to excellent results in SIJ arthropathy in relation to pain relief and functional capacity in long term analysis.

ENDOSCOPIC ELECTROTHERMIC (ESIJ) PROCEDURE OF THE SACROILIAC JOINT 24-MONTH FOLLOW UP STUDIES

Introduction
Patients with low back pain have limitations in functional capacity due impaired back function and kinesiophobia, resulting in worsened functional status, reduced ability to work and quality of life.
The Oswestry Disability Index (ODI) is the most commonly used questionnaire to assess the functional capacity of such patients (Fairbank, Spine 2000). However, it is limited by relying on patient recollection and feedback. Therefore, objective and easy to use validated methods for measuring patients function are required. We evaluated the SPINE device (Epionics Medical GmbH, Potsdam, Germany), which allows the objective assessment of the lumbar spine motion and function in chronic back patients candidate for high-frequency Spinal Cord Stimulation at 10 kHz (HF10 SCS).
Material and Methods:  
Consecutive chronic back pain patients referred to our clinic and candidate for HF10 SCS were assessed pre-SCS trial at 6 weeks 3 months and 6 months post SCS system implantation.
All patients completed an ODI questionnaire and underwent the Epionics measurements in order to measure the range/angle and velocity of motion for pre-defined move- ments, and the age- and genderspecific overall flexibility score.
Epionics SPINE
The Epionics SPINE system is a CE-marked system (Fig. 1) which allows the objective evaluation of movement dynamics and function through the recording of a pre- determined standard choreography and yields information on movement range and dynamics in about 15 minutes (Fig. 2)
Results:  
14 Failed Back Surgery Syndrome patients, including 9 who had undergone fusion, and 2 patients without prior back surgery were assessed.
At baseline, their ODI was 61 ± 4 (mean ± SEM) and 75% of the patients had a poor overall flexibility status as assessed with the SPINE system. All the patients had a successful HF10 SCS trial and were implanted with an Implantable Pulse Generator. During their follow-up, their ODI score decreased from to 37 ± 4 at 6 weeks and 29 ± 4 at 3 months (p<0.001 compared to baseline – Graph 1), with the proportion of patients with severe disability or crippled decreasing from 81% down to 18% at 3 months (Graph. 2)
The Epionics overall flexibility score improved significantly, with the proportion of patients being classified as Poor/Average/ Good improving from 75%/12.5%/12.5% to 33%/13%/53%.at 6 weeks and 0%/28%/ 72%.at 3 months (Graph. 3)
Significant improvements were observed in spinal movement velocities at 6 weeks and 3 months, and in range of motion at 3 months (Graphs 4 and 5)
Conclusion:  
The Epionics functional measurements are easy to perform in routine practice and provide objective, clinically relevant information on lumbar spine function in chronic back pain patients. In SCS patients, this device provides objective information demonstrating the significant impact of HF10 SCS in improving patients function. Further research is needed to confirm these results.

OBJECTIVE MEASUREMENTS OF LUMBAR SPINE FUNCTION IN BACK PAIN PATIENTS UNDERGOING HIGH-FREQUENCY SPINAL CORD STIMULATION AT 10 KHZ

Background
Gender differences in the prevalence of chronic back pain (cBP) have been recorded, but not fully explained. Suggesting gene-by-sex interaction as a possible reason, we explored sex-specific genetic loci for cBP using the UK Biobank. 
Material and methods 
A total of 200,948 males and 236,412 females of European ancestry have been analysed. The phenotype was “Back pain for 3+months”. GWAS were carried out examining males and females separately adjusting for age and technical covariates, followed by a comparisons of SNP effect sizes (regression estimates) between the sexes. 
Results
The prevalence of cBP was 17.7% and 18.2% and the mean age (SD) was 57.5 (8.1) and 57.1 (7.9) in males and females, respectively. Four and 8 non-overlapping genome-wide significant loci were identified for males and females. SNP-explained heritability was higher in females (0.079 vs 0.067, p = 0.006). There was a high genetic correlation between the sexes (r = 0.84, p = 1.7e-94). GWAS comparing the effect size between sexes revealed three significant loci: on chromosomes 4 (rs62327819, SLC10A7), 6 (rs556434841, MEI4), and 8 (rs184345217, CSMD1) (Figure). We found differences in genetic correlations between sexes for four traits: “Neck and shoulder pain”, “Serious illness, injury or assault to yourself”, “Dorsalgia”, and “Self-reported disc problems” (Table).
Conclusions
The results suggest modest differences in the genetic component of cBP in males and females. Their impact of cBP epidemiology are to be explored. 
The study was performed using the UK Biobank data (project # 18219).

SEX-SPECIFIC EFFECTS IN THE GENETICS OF CHRONIC BACK PAIN

Background and aims
During the lead implantation of most neurostimulators, the patient needs to provide adequate feedback, and be with as little pain as possible. Sedation-analgesia can induce this situation. The aim of this study was to provide an overview of the sedation-analgesia regimens of Dutch pain specialists. To this end a questionnaire was sent to them focusing on the sedative agent dexmedetomidine. This sedative has an attractive pharmacological profile and prior research into this drug yielded promising findings during awake procedures.

Methods
The questionnaire was sent to the 65 Dutch pain specialists involved in neurostimulation. The questionnaire consisted of questions concerning different aspects of sedation-analgesia during neurostimulation: the current regimen, the experience with dexmedetomidine and the preferences regarding these different aspects i.e., production of arousable sedation, pain management, quality of patient's feedback and overall preference.

Conclusion:
The most commonly used sedation-analgesia regimen is the combination of propofol-remifentanil during the implantation of a neurostimulator among Dutch pain specialists. Only a small percentage of respondents had experience with the use of dexmedetomidine, despite its reported advantages.

THE SEDATION-ANALGESIA REGIMEN DURING NEUROSTIMULATION AMONG DUTCH PAIN SPECIALISTS

Background and aims: Cinnamaldehyde (CA) elicits itch sensation in humans. Histamine and other itch mediators require expression of TRPV1, TRPA1, and/or TRPV4 in pruriceptor transduction.  We presently investigated if CA-evoked scratching behavior requires TRPV1, TRPA1 and/or TRPV4 using knockout (KO) mice lacking these channels.  We also used calcium imaging to investigate if CA activates sensory dorsal root ganglion (DRG) neurons in wildtype (WT) and KO mice. 
Methods:  We scored hindlimb scratch bouts and forelimb wipes directed to the site of cheek injection of CA in wildtype (WT) and TRPV1, TRPA1 and TRPV4 KO mice.   DRG neurons from each genotype were acutely dissociated, cultured and loaded with FURA-2 for ratiometric calcium imaging of their responses to bath application of CA. 
Results: In WT mice, CA elicited significant, dose-related bouts of hindlimb scratching but not forelimb wiping.   CA-evoked scratching was significantly reduced (~50%)  in TRPV1 and TRPV4KOs but not in TRPA1KOs.  As expected, DRG cells from TRPA1KOs were unresponsive to CA.  Significantly fewer DRG cells from TRPV4KOs were activated by CA, consistent with the behavioral data.  Curiously, significantly more DRG cells from TRPV1KOs vs. WTs were activated by CA.   
Conclusions: TRPA1 is not required for CA-evoked itch behavior.  TRPV4 in sensory neurons is important for CA-evoked itch, since scratching and DRG neuronal responses were both reduced in TRPV4KOs.  TRPV1 is also important for CA-evoked itch; however, since CA activated DRG cells from TRPV1KOs, TRPV1 may have a role in itch independent of sensory neurons.  
Acknowledgment: supported by NIH ARO57194

CINNAMALDEHYDE-EVOKED SCRATCHING IN MICE REQUIRES DIRECT OR INDIRECT ACTIVATION OF TRPV4- AND TRPV1- BUT NOT TRPA1-EXPRESSING SENSORY NEURONS

ROLE OF HEPARIN IN ENHANCING THE SKIN PENETRATION AND PAIN RELIEF FROM DICLOFENAC EPOLAMINE (DHEP) MEDICATED PLASTER
K.D.Rainsford 1, S.Rovati 2, A.Nencioni 3, C.Jones 4
1 Biomedical Research Centre, Sheffield Hallam University, Sheffield, S1 1WB, UK
2 R&D and Scientific Affairs, IBSA Institut Biochimique, Pambio-Noranco, Lugano, Switzerland, 
3 Pharmaceutical R&D, IBSA Institut Biochimique, Manno, Lugano, Switzerland
4 Scientific Advisor, IBSA Pharma Inc., Washington D.C., USA.

BACKGROUND & AIMS: Topical NSAIDs are effective in the treatment of musculo-skeletal inflammation/pain, while at the same time reducing the risk of systemic AEs. Among NSAIDs topical formulations, diclofenac epolamine (DHEP) medicated plaster was found amongst the most effective. Recently, the incorporation of heparin into the DHEP medicated plaster was developed with the aim to enhance diclofenac penetration to the site of inflammation. 
METHODS: (1) Heparin residual content in the medicated plaster was measured after 24-hour application in healthy volunteers participating in a PK (BA) study; (2) The release and permeation of DHEP from medicated plasters formulated with and without heparin were compared in a Franz cell diffusion system using different membranes. 
RESULTS:  (1) No pre-/post-application change in plaster heparin content was observed following 24-hour application in vivo, showing that heparin release from the plaster is negligible, if any, while at the same time DHEP content was substantially reduced; (2) Permeation profiles in Franz cells showed that both the amount and rate of DHEP release from heparin-containing plasters was significantly greater as compared to the reference formulation without heparin.
CONCLUSIONS: In vitro and in vivo data demonstrated that heparin is not released from the DHEP plaster formulation after topical application. This suggests that heparin works as permeability enhancer, increasing the release and skin penetration of diclofenac, thus providing an explanation for the significantly greater analgesic efficacy of the DHEP heparin plaster vs the DHEP plaster without heparin in clinical trials.

ROLE OF HEPARIN IN ENHANCING THE SKIN PENETRATION AND PAIN RELIEF FROM DICLOFENAC EPOLAMINE (DHEP) MEDICATED PLASTER

A 47-year old female patient with failed back surgery syndrome (FBSS) resulting in chronic low back and bilateral leg pain of 7-8/10 on the numeric rating scale (NRS) was treated with 10 kHz spinal cord stimulation (HF10-SCS) and coincidentally reported improvement in bladder function from this therapy. At presentation, she was experiencing incontinence and self-catheterizing 4-5 times a day due to overactive bladder refractory to Botox injections. The Incontinence Impact Questionnaire (IIQ-7) and Urogenital Distress Inventory (UDI-6) scores at baseline were 80/100 and 67/100, respectively.
A successful 2-week HF10-SCS trial with percutaneous leads resulted in 80% pain reduction, NRS improvements for low back (2-3), bilateral buttock (0) and leg (0), ability to sleep through the night, mood improvement and reduced need for self-catheterization. During the 5 weeks between trial and permanent implant, both pain and bladder function returned back to baseline. Once implanted, symptoms improved again to end-of-trial values. At the last follow-up (10 months) 70% pain reduction was reported with NRS of 2, 1 and 1 for low back, bilateral buttock and leg, respectively. IIQ-7 and UDI-6 scores improved substantially to 9 and 21, respectively. Self-catheterization frequency was reduced by over a half, accompanied by a sharp decrease in urinary tract infections.

IMPROVEMENT IN BLADDER FUNCTION FOLLOWING HIGH-FREQUENCY SPINAL CORD STIMULATION AT 10 KHZ: A CASE REPORT

Background and aims:
Patients using SCS systems who have endured problems with device longevity and/or loss of efficacy may be able to achieve better outcomes utilizing newer technologies that offer an increased variety of waveforms and programming options to address their chronic pain. In this retrospective study, we examined the outcomes of previously-implanted patients who went on to use a commercially-available adaptor enabling connection to an SCS system that offers multiple neurostimulation based treatment approaches to regain and maintain efficacious therapy.

Materials / Methods: 
This is a real-world, retrospective study of patients who were previously implanted with an SCS system (commercially-available SCS device, Abbott) who then went on to utilize an adaptor (Precision S8, Boston Scientific) to connect to a new SCS system capable of multiple modality stimulation and/or combination therapy. Pain relief and other associated outcomes with both previously-implanted SCS systems and newly connected commercially¬ available systems (Boston Scientific) are being collected.

Results:
Data from a total of 8 patients who provided all pain scores have been collected and analyzed to date. Six of 8 patients utilizing a device adaptor reported better pain relief after connection to and use of a multiple waveform SCS system (i.e. pain scores after using current versus previous system at post-baseline follow-up assessment). A mean 4.7 ± 1.9 point improvement was reported using the current system versus a 2.3 ± 2.8 point improvement using the previous system. Data from additional patients in this ongoing case-series will be presented. 

Conclusions:
In this small, multi-center case-series, no patients reported better pain relief using the previous system versus their current system (multiple waveform SCS) when using a device adaptor. The results of this preliminary study suggest that offering previously implanted SCS patients a system capable of providing multiple waveforms can improve pain relief.

OUTCOMES FOLLOWING UTILIZATION OF A DEVICE ADAPTOR IN PREVIOUSLY-IMPLANTED PATIENTS USING SCS FOR CHRONIC PAIN

Background and aims
Spinal Cord Stimulation (SCS) devices that enable personalized fine-tuning of stimulation parameters or waveforms offer the potential to address the variability among chronic pain patients.  We endeavored to clinically investigate this system by evaluating the outcomes associated with use of multiple neurostimulation modalities as compared with conventional SCS settings alone in a prospective, randomized controlled trial.

Materials / Methods
COMBO is a prospective, multicenter, randomized controlled trial with an adaptive design (Clinicaltrials.gov identifier: NCT03689920). The primary endpoint of the study is based on the proportion of subjects, permanently implanted with an SCS system capable of multiple neurostimulation modalities (Spectra WaveWriter, Boston Scientific), demonstrating ≥50% reduction from Baseline in average overall pain intensity at 3-month follow up. Additional endpoints will assess quality of life, disability etc. Adverse events will also be collected.  

Results
Real-world data utilizing the same SCS System demonstrated, in a cohort of 312 subjects, a statistically significant improvement in overall targeted pain scores (NRS) at last follow up (7.3 [baseline] to 2.1 [last follow-up with mean 106 days]). This improvement was also noted at 3 and 12 months follow-up (p < 0.0001). Data collection and analysis using the same SCS system in this RCT are ongoing at up to 15 centers. Preliminary analysis to be presented.

Conclusions:
Outcomes of a prospective, randomized controlled trial offer the opportunity to provide Level 1 evidence related to the use of an SCS system capable of multiple neurostimulation modalities in the treatment of chronic pain, while minimizing bias and confounding effects resulting from differences in patient selection, demographic variables, investigator technique and/or patient management. The COMBO randomized controlled trial will evaluate the clinical effectiveness of multiple neurostimulation modalities of SCS (versus conventional SCS settings) used in treatment of chronic pain.

OUTCOMES OF A PROSPECTIVE RANDOMIZED CONTROLLED TRIAL UTILIZING A SPINAL CORD SYSTEM CAPABLE OF MULTIPLE NEUROSTIMULATION MODALITIES (COMBO STUDY)

Background and aims: Excitability of pain-processing areas and response to incoming somatosensory stimuli are abnormally enhanced in Fibromyalgia(FM). To explore if such facilitation represents a more general sensorial activation not strictly related to pain, we evaluated excitability of visual cortex, an area not directly involved in pain processing, through Sound-Induced Flash Illusion(SIFI)(1). SIFI are cross-modal illusions, strictly dependent upon visual excitability, where visual perception is influenced by auditory input. When a single flash is accompanied by multiple beeps, it is perceived as multiple flashes(fission illusion), conversely when 2 flashes are accompanied by one beep, they are perceived as one (fusion illusion). SIFI are reduced when visual cortical excitability increases.
Methods: We performed SIFI in 19(18 F)  FM patients and 24 healthy controls(16 F). Throughout the test, 0 -4 flash were presented on a monitor together with 0-4 beeps delivered by loud-speakers, in different combinations. The observer’s task was to judge the number of flashes seen.
Results: Preliminary data show a highly significant reduction in fission illusions in FM patients compared to healthy controls(particularly when 1 flash is accompanied by three or four beeps, p<.0005).
Conclusions: Our results suggest an increased visual excitability that could favor the hypothesis of a general sensorial activation, non strictly linked to pain, in FM. This could make more light on pathophysiological mechanisms of disease likely opening also new ways for treatment. SIFI represent an easy and effective tool to explore cross-modal audio-visual perception and visual cortical excitability in FM patients.

1.Shams et al. Nature.2000,408:788

Note: authors of this abstract have nothing to disclose.

VISUAL CORTICAL EXCITABILITY IN FIBROMYALGIC PATIENTS: A STUDY WITH SOUND INDUCED FLASH ILLUSION

Background and aims. The main objective of this study is to identify fibromyalgia syndrome (FMS) clusters using the Revised Fibromyalgia Impact Questionnaire (FIQR); and to examine whether the clusters differ in demographic data, clinical measures, direct and indirect costs, levels of inflammatory markers and brain morphometry.
Methods. A hierarchical cluster analysis was performed to classify a large, pooled Spanish sample of patients with FMS (N= 947) using the FIQR as clustering variable. A latent profile analysis was subsequently conducted to confirm the optimal number of FMS clusters. To examine external validity, a battery of clinical measures, economic costs, inflammatory markers and gray matter volumes of relevant cortical and subcortical areas were analyzed. We also compared the discriminant validity of the clusters with the original FIQR severity categories. To promote the implementation in real-world clinical practice, we built a free online cluster calculator.
Results. Our findings indicated that a four-cluster solution more clearly captured the heterogeneity of FIQR data and provided the best fit. This cluster solution allowed detection of differences for most clinical outcomes and economic costs. Regarding the inflammatory and brain-based biomarkers, differences were found in C-reactive protein, and tendencies were found in the right medial prefrontal cortex, the right parahippocampal gyrus, and the right middle cingulate cortex; brain regions associated with executive functions and pain processing. The original FIQR categories presented similar results, although their precision in discriminating among the non-extreme categories was not sound.
Conclusions. These findings are discussed in relation to previous research on FMS clustering.

CLUSTERING PATIENTS WITH FIBROMYALGIA USING THE FIBROMYALGIA IMPACT QUESTIONNAIRE REVISED (FIQR): DIFFERENCES IN CLINICAL OUTCOMES, ECONOMIC COSTS, INFLAMMATORY MARKERS AND GRAY MATTER VOLUMES

Background and aims: NA is an uncommon and underdiagnosed cause of new-onset pain in the shoulder (1). 
It starts with a phase of intense and refractory pain (PP) to conventional analgesics, followed by a phase of neurogenic atrophy (PNA) of specific muscles. Specific treatment doesn´t exist yet. We report a case who responded to intravenous lidocaine (IL) and amitriptyline. 

Method: A 40- year-old man reported a shoulder neuropathic pain. A recent parvovirus B19 infection was confirmed. Treatment with prednisone, dexketoprofen, pregabalin, and fentanil was initiated but proved ineffective. On day 15 a round of 10 days of lidocaine infusion (LI) was initiated. After 15 days he was discharged and we prescribed amitriptyline 50 mg, on which he showed a 50% improvement. 
During the following week, he started PNA in the right shoulder, while PP persisted in the left one, which made rehabilitation difficult, so we started a new round of LI with an improvement that facilitated rehabilitation. 

Discussion: There is increasing knowledge about NA but not about its pain treatment. LI has shown efficacy in refractory neuropathic pain (2). Amitriptyline has proven useful in neuropathic and musculoskeletal pain (3).

Conclusion: Further study is needed to evaluate the best analgesic treatment in NA. 

1. Eijk J et al. NA, An update on diagnosis, pathophysiology and treatment. Muscle and nerve. 2016. 
2. IL for chronic pain. CADTH. 2018. 
3. Driest JJ et al. Amitriptyline for musculoskeletal complaints: a systematic review. Farm Pract 2017.

Please address correspondence to: 
Carlos Agreda Garcia: cagredag@gmail.com

PAIN SÍNDROME IN NEURALGIC AMYOTROPHY (NA) OR PARSONAGE-TURNER SÍNDROME, DO WE HAVE IT UNDER CONTROL? A CASE REPORT

Background: 
Visual disability and neuropathy, along with chronic neuropathic pain in poorly controlled diabetes amplify sensitivity to rejection, making it possible to construct non-bizarre delirium, favoring the development of an Organic Personality Disorder that overlaps an organic delusional disorder.
Presentation of a 74-year-old patient at first admission to psychiatry for bizarre expansive behavioral manifestations, due to the paranoid clinical picture, comorbid with chronic pain due to diabetic polyneuropathy and retinopathy of the same etiology.
The vulnerable structure (early strength myopia) and the transgenerational stigma make, with the advancing of visual impairment and with the accentuation of neuropathic pain, the patient disorganizes his thinking and behavior, becoming delusional. In the alternative, there is major depression, doubled by suicide risk.
Methods: Clinical Interview, Hetero-anamnesis, Cerebral CT and Computerized EEG (which confirm organicity), psychological testing, psychiatric monitoring, assays of diagnostic assumptions, psychodynamic interpretations.
Results: The diagnosis of organic delusional disorder with differential diagnoses of Organic Personality Disorder and Parafrenia is explained and supported. From psychodynamic point of view, the patient's functioning is marked by immature denial defense mechanisms and psychotic projection, along with black humor. The patient presents suspiciousness, delirious interpretativity, emotional ambivalence, tangential thinking and circumstantiality, a delusional idea of relationship, persecution and prejudice that alters his or her attitudes and reporting to the world and life.
Conclusions: Defensive mechanisms that have once been beneficial and have facilitated acceptance of the vision deficiency condition (from the Hyperstezia Register and other senses area) have now escalated to sensory delirium phenomenology of relationship.