Higher Pain Reduction Research Articles

Intranasal Fentanyl Versus Morphine in Fracture Reduction in a Pediatric Trauma Center.

Pain management in orthopaedic manipulation in the emergency department (ED) is crucial to decrease fracture reduction performed in the operating room. This study compared intranasal fentanyl (INF) with oral morphine in time of care and effectiveness on pain during the reduction of bone fractures in a pediatric trauma center. A before-and-after INF implementation study was conducted in a pediatric ED with a trauma center on children with a confirmed displaced closed fracture on radiographs with reduction and casting performed in the ED. The time of care, time for sufficient analgesia, effectiveness on pain, and tolerance were compared between both analgesics in 3 consecutive phases. 77 children were included: 31 children received oral morphine and 46 INF. The time of care was shorter in the INF group (150 [111 to 193] minutes versus 215 [155 to 240], P = 0.01) as the time for sufficient analgesia (10 [9 to 13] minutes versus 80 [53 to 119], P < 0.001) with a higher pain reduction after a dose of INF (3 [0 to 4] versus 6 [3 to 7], P < 0.001) and less dose requirement (P = 0.002). Although pain scores were similar at arrival in both groups (P = 0.15), the pain was significantly lower before and during the procedure in the INF group and equivalent after the procedure (2 [0 to 4] versus 3 [0 to 5], P = 0.02, 3 [1 to 5] versus 7 [3 to 9], P < 0.001, and 1 [0 to 2] in both groups, P = 0.87, respectively). Keeping pain levels low during the procedure in the INF group allowed the extension to lower limb fracture reductions (P = 0.04). No serious adverse events were reported. INF reduces the time to obtain sufficient analgesia and time of care, with good effectiveness maintained during the procedure in fracture reduction, allowing the extension to lower limb fractures. Thus, this rapid and efficient analgesia facilitates orthopaedic care in the pediatric ED that would otherwise require to be reduced in the operating room under general anesthesia.

Ganglionic Local Opioid Analgesia at the Superior Cervical Ganglion: MRI-Verified Solution Spread.

Ganglionic local opioid analgesia (GLOA) at the superior cervical ganglion (SCG) is performed for pain control and is known to be an effective procedure. In this study, we evaluated the spread of the injectate in the area of the SCG. Our expectation was that there would be a correlation between the area and volume of the injectate spread and post-procedural outcome measures. This was a retrospective blinded review of magnetic resonance imaging (MRI) scans. Assessors evaluated the anatomical area of fluid spread, the furthermost spread from midline, any hampered spread and contact of contrast fluid with other structures. The efficacy of GLOA and complications were estimated. The main solution spread reached from the C1 to C3 vertebrae. The furthest spread in the lateral and sagittal planes was 21.2 and 15.2mm, respectively. The furthest craniocaudal spread was 63.5mm. In 53.3% and 33% of interventions, the solution was found in the parapharyngeal space and in its "medial compartment," respectively. A correlation was found between pain relief and both solution spread and volume of solution spread. No hampered spread was recorded. A negative correlation between pain reduction and number of GLOA was observed. Higher pre-procedural pain intensity was correlated with higher pain reduction. We estimated pain relief in 93% of procedures correctly. No correlation between post-procedural Numerical Rating Scale (NRS) scores and different needle approaches was found. For the transoral blocking technique, a strict laterodorsal needle direction is recommended to prevent possible block failures. A total volume of 2ml injected into the parapharyngeal space and its "medial compartment" is recommended. Higher volumes may lead to uncontrolled distribution patterns. Clinicaltrials.gov identifier NCT05257655; date of registration 2022-02-25; patient enrollment date from 2023-01-09 to 2023-08-31.

Effect of Trunk-Focused Exercises on Pain, Disability, Quality of Life, and Trunk Physical Fitness in Low Back Pain and How Potential Effect Modifiers Modulate Their Effects: A Systematic Review With Meta-analyses.

OBJECTIVE: To analyze the effect of trunkfocused exercise programs (TEPs) and moderator factors on chronic nonspecific low back pain (LBP). DESIGN: Systematic review with meta-analyses. LITERATURE SEARCH: We searched the PubMed, Scopus, Embase, SPORTDiscus, and CENTRAL databases from their inception to June 2022. STUDY SELECTION CRITERIA: We included randomized controlled trials comparing TEPs to control or general exercises. DATA SYNTHESIS: We used random-effects models to calculate the standardized mean difference (SMD) plus confidence interval (CI) and heterogeneity (I2) for pain, disability, quality of life, and trunk performance. The impact of moderator factors was analyzed through meta-regression. RESULTS: Forty randomized controlled trials (n = 2391) were included. TEPs showed positive effects for all outcomes versus control (SMD 0.90-2.46; 95% CI, -0.04 to 4.96; I2 61%-98%). There were small effects in favor of TEPs versus general exercises for pain (SMD = 0.20; 95% CI, 0.03-0.37; I2 = 13.4%) and disability (SMD = 0.20; 95% CI, 0.02-0.38; I2 = 0%). Trunk and/or hip range-of-motion improvements were associated with greater reductions in pain (P<.01; β = 0.56; 95% CI, 0.25-0.87) and disability (P<.01; β = 0.66; 95% CI, 0.27-1.05). Low body mass was associated with higher pain reduction (P = .03; β = -0.17; 95% CI, -0.32 to -0.02). CONCLUSIONS: Trunk-focused exercise programs had positive effects on pain, disability, quality of life, and trunk performance compared to control groups, and on pain and disability compared to general exercises. Increasing trunk and/or hip range of motion was associated with greater pain and disability reduction, and lower body mass with higher pain reduction. J Orthop Sports Phys Ther 2023;53(2):64-93. Epub: 16 January 2023. doi:10.2519/jospt.2023.11091.

Pain reduction and adverse effects of intravenous metoclopramide for acute migraine attack: A systematic review and meta-analysis of randomized-controlled trials.

BACKGROUNDMetoclopramide may be used to treat people suffering from acute migraine. However, no comprehensive investigation on this issue has been recorded. This review will provide more solid evidence for the use of metoclopramide in treating acute migraine.AIMTo compare the efficacy of intravenous metoclopramide with other therapies in migraine attack treatment in an emergency department (ED).METHODSWe included randomized controlled trials of participants older than 18 years with acute migraine headaches, which included at least one arm that received intravenous (IV) metoclopramide at the ED. A literature search of PubMed, Web of Science, Cochrane Collaboration, and Reference Citation Analysis on December 31, 2021 retrieved other drugs or placebo-controlled studies without language limitation. The risk of bias was assessed using the Cochrane risk of bias tool. The primary endpoint was pain reduction at 60 min or closest to 1 h after treatment, as measured by the pain scale. Secondary endpoints included adverse effects or reactions resulting from metoclopramide or comparisons.RESULTSFourteen trials with a total of 1661 individuals were eligible for review. The risk of bias ranged from low to intermediate. IV metoclopramide administration was not associated with higher pain reduction at 1 h (Standard mean difference [SMD] = -0.03, 95% confidence interval [CI]: -0.33-0.28, P = 0.87). However, metoclopramide was associated with better pain reduction than placebo (SMD = 1.04, 95%CI: 0.50-1.58, P = 0.0002). In addition, side effects were not significantly different between IV metoclopramide and other drugs or placebo (odds ratio [OR] = 0.76, 95%CI: 0.48-1.19, P = 0.09 and OR = 0.92, 95%CI: 0.31-2.74, P = 0.54, respectively).CONCLUSIONMetoclopramide is more effective than placebo in treating migraine in the ED. Despite the observed tendency of decreased side effects, its effectiveness compared to other regimens is poorly understood. More research on this area is needed to treat migraine in acute care settings effectively.

CT-Guided Coeliac Plexus Neurolysis in Patients with Intra-Abdominal Malignancy: A Retrospective Evaluation of 52 Palliative In-Patients.

IntroductionPrevalence rates of chronic abdominal pain (CAP) and breakthrough cancer pain (BTcP) are high in patients with intra-abdominal malignancies. As part of a multimodal approach, CT-guided coeliac plexus blockade (CPB) and CT-guided coeliac plexus neurolysis (CPN) are commonly used pain management strategies. The aim of this study was to evaluate pain outcomes among patients with intra-abdominal malignancies who underwent CPB and/or CPN.MethodsPatients with intra-abdominal malignancies who underwent CPB and/or CPN for pain control at the general hospital Klagenfurt am Wörthersee from 2010 to 2019 were enrolled.ResultsA total of 84 procedures (24 CPB and 60 CPN) were performed on 52 patients; 62% of these patients had pancreatic cancer. CPN led to significant pain reduction and decreased BTcP intensity. Patients receiving repeated CPN showed higher individual pain reduction. Higher pre-procedural pain intensity was correlated with higher pain reduction. No difference in pain reduction in patients receiving a diagnostic CPB prior to CPN compared to patients without a diagnostic CPB was found. Higher pain reduction after CPN led to longer-lasting pain relief. The time frame from diagnosis to CPN was 472 (± 416) days. Patients experienced a mean duration of pain prior to CPN of 330 (± 53) days. The time frame from diagnosis to CPN was shorter in patients with pancreatic cancer compared to other intra-abdominal malignancies. In 58% of patients pain medication was stable or was reduced after CPN; 16% of patients complained about pain during the procedure; no major complications occurred. There was no correlation between median survival after CPN and pain outcomes.ConclusionsIn patients with intra-abdominal malignancy-related CAP, CPN is a safe and effective procedure which can provide long-lasting significant relief of background pain and BTcP. As part of a multimodal approach, CPN should be considered as an earlier option for pain management in these patients.

Baseline pain characteristics predict pain reduction after physical therapy in women with chronic pelvic pain. Secondary analysis of data from a randomized controlled trial.

Background and aims Women with chronic pelvic pain represent a heterogeneous group, and it is suggested that the existence of sub-groups can explain varying results and inconclusiveness in clinical trials. Some predictors of treatment outcome are suggested, but the evidence is limited. The primary aim of this study was to explore if selected pre-treatment characteristics of the participants in a recently conducted randomized controlled trial were associated with treatment outcome. Methods In this study secondary analysis of data collected in a randomized trial were conducted. The participants were women with chronic pelvic pain randomized to two different physical therapy treatments. Analyses in this study were performed for the whole group as a cohort. The primary outcome measure was change in pain intensity from baseline to 12 months, measured with the numeric rating scale (0-10). The women were asked to rate their mean pelvic pain intensity during the last 7 days. Based on previous research and on available variables from the randomized controlled trial four potential predictive factors were derived from the baseline data and assessed one by one in a linear regression model, adjusted for age and treatment group. The variables with strongest association (p < 0.10) with the primary outcome were further included in a multivariable linear regression model with backward selection, adjusted for age and treatment group. Results Fifty women (mean age 38.1, SD = 12.2) were included in the analysis. For these women the mean change in pain intensity was -1.2 points (95% CI -1.8 to -0.7) from baseline to 12 months. The multivariable regression model showed that pelvic pain duration of 6 years or more was associated with less decrease in pain intensity with a regression coefficient of 1.3 (95% CI 0.3-2.4). Baseline pain intensity was associated with higher pain reduction after PT treatment with a regression coefficient per SD increase in baseline pain of -0.6 (95% CI -1.1 to -0.1). None of the women with main pain site other places than in the pelvis reported any pain reduction after physical therapy treatment, but due to the small numbers the predictor was not included in the regression analysis. Conclusions We identified that pelvic pain duration of 6 years or more was associated with less pain reduction, and that higher baseline pain intensity was associated with higher pain reduction after physical therapy treatment in this sample of women with chronic pelvic pain. For the variable main pain site other places than the pelvis the results are unsure due to small numbers. Implications Based on our finding of long pain duration as a negative predictor for pain reduction, we emphasize that early intervention is important. Many of the participants in our RCT reported pelvic surgeries or other treatments prior to referral for PT, and we suggest that referral to a non-invasive intervention such as PT should be considered at an earlier stage. In order to tailor interventions to the individual women's needs, thorough baseline assessments, preferably in a multidisciplinary setting, should be performed.

Timing of kyphoplasty influences the outcome: a prospective study

The aim of this prospective study was to evaluate the efficiency of early versus delayed treatment of vertebral fractures by balloon kyphoplasty with regard to fracture age. A total of 106 patients (37 male and 69 female) with 128 vertebral body fractures, an average age of 67.5 years (21 to 92) and a body mass index of 26.4 (16 to 40.4) were recorded. All fractures were evaluated radiologically and clinically. Pain intensity (visual analogue scale 0-10), analgesics consumption (WHO steps 1 to 3) and the relevant surgery data (operating time, cement consumption, complications) were recorded. 37 A 1.1, 43 A 1.2, 43 A 1.3, 4 A 3.1 and 1 A 2.3 classifications were collected. Fracture age in days was less than 23 days in 75 patients; the mean time of surgery was 43 minutes. Analgesics consumption was reduced from 1.8 ± 0.8 preoperatively to 1.0 ± 0.6 postoperatively. A significant improvement was found in pain intensity, which fell significantly from 8.2 ± 0.9 preoperatively to 3.9 ± 0.8 postoperatively. In relation to fracture age and pain intensity, a significantly higher pain reduction was achieved with timing of kyphoplasty between 0 and 23 days. Here, pain intensity decreased to 2.5 ± 0.5 postoperatively, compared with 4.5 ± 0.4 for fractures treated later. Fracture age had no influence on vertebral body alignment or improvement of the kyphotic angle. In summary, it can be stated that balloon kyphoplasty is a sufficient method to treat vertebral body fractures, to improve the kyphotic angle and reduce pain significantly.

Analgesia (mis)usage on a dental emergency service: a patient survey.

Analgesics are one of the most frequently used medicines. Self-medication and misuse have been described in the literature. The purpose of this study was to document analgesic (mis)use in a population seeking emergency dental treatment. Patients consulting a dental emergency service were randomly asked to complete a questionnaire on analgesic use, knowledge and information on the analgesics and on their pain history. A photobook was used as an aid to identify products used. Descriptive statistics were combined with chi-square and Mann-Whitney U testing. Ninety-eight patients were included. Acetaminophen (69.4%) and ibuprofen (65.3%) were the most frequently used products. Nearly half of the subjects (43.9%) combined at least two analgesics. Although 42.9% of subjects were aware of the maximum daily dose, 62.2% of the subjects exceeded this limit, specifically 76.6% of subjects using ibuprofen and 32.4% of subjects using acetaminophen overdosing. Females overdosed significantly more than males. Ingestion on medical advice did not affect the overdose rates significantly. No significant relation was found between the absence of knowledge on the maximum daily dose and actual overdosing. No higher pain reduction was found in patients overdosing analgesics. The average number of days patients experienced pain before consulting the emergency unit was 12. A significant relation was found between the lag time and overdosing. A large portion of the patients overdosed analgesics. Even prior medical advice did not reduce significantly overdose rates. Dentists treating emergency cases clearly need to be aware of the high risk and high rates of overdosing analgesics in their patients.

High-dose 8% capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy: single-center experience

High-dose capsaicin patch is effective in treatment of neuropathic pain in HIV-associated neuropathy and diabetic neuropathy. There are no studies assessing effectiveness of high-dose capsaicin patch in treatment of chemotherapy-induced peripheral neuropathy. We sought to determine the effectiveness of treatment of pain associated with chemotherapy-induced peripheral neuropathy with high-dose capsaicin patch. Our study group consisted of 18 patients with clinically confirmed oxaliplatin-induced neuropathy. Baseline characteristic including underling disease, received cumulative dose of neurotoxic agent, neuropathic symptoms, prior treatment and initial pain level were recorded. Pain was evaluated with Numeric Rating Scale prior to treatment with high-dose capsaicin and after 1.8 day and after 8 and 12 weeks after introducing treatment. Patients were divided into two groups accordingly to the amount of neurotoxic agent that caused neuropathy (high sensitivity and low sensitivity group). Most frequent symptoms of chemotherapy-induced neuropathy were: pain (88.89%), paresthesis (100%), sock and gloves sensation (100%) and hypoesthesis (100%). Initial pain level was 7.45 ± 1.14. Mean cumulative dose of oxaliplatin after which patients developed symptoms was 648.07 mg/m2. Mean pain level after 12 weeks of treatment was 0.20 ± 0.41. When examined according to high and low sensitivity to neurotoxic agent patients with low sensitivity had higher pain reduction, especially after 8 days after introducing treatment (69.55 ± 12.09 vs. 49.40 ± 20.34%; p = 0.02) and after 12 weeks (96.96 ± 5.56 vs. 83.93 ± 18.59%; p = 0.04). High-dose capsaicin patch is an effective treatment for pain associated with chemotherapy-induced neuropathy in patients treated with oxaliplatin. Patients with lower sensitivity to neurotoxic agents have better response to treatment and pain reduction.

Relationship of specific MRI findings to treatment outcomes in patients receiving transforaminal epidural steroid injections

To determine whether specific MRI findings are related to outcomes after lumbar transforaminal epidural steroid injections (TFESI) and to assess the inter-rater reliability of imaging diagnosis. A prospective outcomes study on 156 consecutive patients with 1-month follow-up outcomes data and MRI within 3months of TFESI was conducted. Pain levels (numerical rating scale) (NRS) were recorded prior to injection. Overall 'improvement' was determined using the Patients Global Impression of Change (PGIC) scale and NRS data were collected at three time points post injection. Two radiologists independently evaluated all images blinded to treatment outcome for reliability of diagnosis. The Chi-square test compared MRI findings for the senior radiologist to 'improvement'. NRS change scores were compared to MRI findings with the unpaired t-test or ANOVA. Kappa and percent agreement assessed inter-rater agreement of diagnosis. The only abnormality linked to 'improvement' (p = 0.03) and higher NRS change scores (p = 0.0001) at 1month was the disc herniation morphology 'protrusion + sequestration'. Patients with degeneration by osteophytes (p = 0.034), grade 3 foraminal nerve root compression (p = 0.01) and foraminal/extraforaminal location of herniation (p = 0.014) also had higher 1month NRS change scores. Reliability of diagnosis was 'fair' to 'substantial' depending on MRI findings. Patients with disc protrusion plus sequestration were significantly more likely to report overall improvement and more pain reduction at 1month. Higher pain reduction was noted in patients with degeneration by osteophytes, grade 3 foraminal nerve root compression, or foraminal/extraforaminal disc herniation location.

Remifentanil versus Fentanyl/Midazolam in Painless Reduction of Anterior Shoulder Dislocation; a Randomized Clinical Trial.

Performance of painful diagnostic and therapeutic procedures is common in emergency department (ED), and procedural sedation and analgesia (PSA) is a fundamental skill for every emergency physician. This study was aim to compare the efficacy ofremifentanil with fentanyl/midazolam in painless reduction of anteriorshoulder dislocation. In this randomized, double blind, clinical trial the procedural characteristics, patients' satisfaction as well as adverse events were compared between fentanyl/midazolam and remifentanil for PSA of 18-64 years old patients, which were presented to ED following anterior shoulder dislocation. 96 cases were randomly allocated to two groups (86.5% male). There were no significant difference between groups regarding baseline characteristics. Remifentanil group had lower duration of procedure (2.5 ± 1.6 versus 4.6 ± 1.8 minutes, p < 0.001), higher pain reduction (53.7 ± 13.3 versus 33.5 ± 19.6, p < 0.001), lower failure rate (1 (2.1%) versus 15 (31.3%), p < 0.001), higher satisfaction (p = 0.005). Adverse events were seen in 12 (25%) patients in midazolam/fentanyl and 8 (16.7%) cases in remifentanil group (p = 0.122). It seems that use of remifentanil resulted in lower procedural time, lower failure rate, and lower pain during procedure as well as higher patient satisfaction in comparison with midazolam/fentanyl combination in anterior shoulder dislocation.

Effect of intravenous continual vs. Bolus doses of tramadol and metamizol sodium combination in acute pain management: Continual vs. Bolus doses of tramadol and metamizol combination: Pilot study

Introduction: Tramadol and metamizol are very commonly used postoperatively for acute pain (bolus doses). Combined iv infusion tramadol/metamizol provide safe and effective acute pain relief and there is no evidence for pharmacokinetic and pharmacodynamic side effects in clinical practice. Morphine sulfate seems to be the best rescue analgesic for patients receiving this infusion. Methods: After approval of local ethic committee and written ICF, the prospective cohort pilot study included all patients undergoing surgery (radical nephrectomy with lumbotomy approach). ASA physical status I to III and normal minimental score patients were included. Patients suffered from diabetes melitus, depressive disorders, advanced renal failure, hematology disease, peptic ulcer, drug abuse or chronic opioid use, medicament allergic reaction were excluded. All patients who underwent surgery under general anesthesia recieved the same premedication. Anaesthesia induction was made with propofol in dose 2 mg/ kg followed by sevoflurane (1MAC), fentanyl (0,005 mg/ kg) and rocuronium 0,6 mg/kg for intubation. Complications of surgical procedures have not occurred. Postoperatively, patients were randomized into two groups. Group I received iv infusion of tramadol 100 mg qd and metamizol -Na 2500 mg bid in bolus doses. Analgesia started with tramadol 100 mg followed by metamizol 2500 mg after 120 minutes. Group II received the solution tramadol 400 mg (0,8 mg/ml) and metamizol 5000 mg (10 mg/ml) in 500 ml normal saline. Infusion rate was 200 ml/h first 30 minutes followed with 17 ml/h infusion rate for maintenance until end of infusion. For both group of patients administration of analgesia started 15 minutes after awakeing. Patient related data were compared between two groups as well as pain scores, analgesic consumption and rescue medication if it was necessary. If pain intensity score was above 7/10 by VAS, patients in both groups received rescue dose of 0,025 mg/kg morphine sulfate. Prophylactic doses of metoclopramide 10 mg tid were administered to prevent nausea. Vital signs, body temperature, sedation scores, emetic episodes, therapy side effects and volume loss were recorded. Results: In Group I, 11 patients were randomized, mean age 59 ± 8,95. Regarding gender there were 6 male and 5 female patients. In Group II, 12 patients were randomized, mean age 62,2± 9,51. Regarding gender there were 7 male and 5 female. There was no difference in demographic caracteristics, duration of surgery and intraoperative blood loss between two groups. We found difference in group II patients (p = 3.42, p < 0,01) regarding weight. In group I no difference was found. Average VAS was similar in both groups. Male patients reported higher initial pain score but also higher pain reduction with no age difference in both groups. Patients in group I reached good pain control (VAS ≤ 3) in 8th, while patients in group II reached it in 2nd hour postoperatively. We administered higher doses of analgesics in group I (tramadol 2.58 mg/kg, metamizol 32.28 mg/kg) than in group II (tramadol 1.24 mg/kg, metamizol 15.72 mg/kg). In group I, 45% of patients required rescue analgesia. There was no patients in group II that required rescue analgesia. In patients with significant intraoperative blood loss, additional consumption of rescue analgesia did not occurred. There was no therapy side effects. Conclusion: Administration of combined lower dose tramadol/metamizol in continual infusion provides faster onset and better postoperative analgesia with no consumption of rescue analgesics compared to tramadol/metamizol given individually (in bolus doses).

Dual Reuptake Inhibitor Milnacipran and Spinal Pain Pathways in Fibromyalgia Patients: A Randomized, Double-Blind, Placebo-Controlled Trial

Background: Investigations based on quantitative sensory testing have consistently shown evidence of allodynia in fibromyalgia syndrome (FMS) patients involving both the spinal and supraspinal pain regulatory systems. Functional imaging studies have demonstrated enhanced neural activities in painrelated brain areas as well as impairment of pain inhibition in the descending nociceptive regulatory system. A higher state of excitability of spinal nociceptive neurons as evidenced by lowered nociceptive flexion reflex R-III (NFR) threshold was reported for FMS patients. The NFR procedure has been shown to be a valuable tool to evaluate pharmacologically active therapeutic agents at the spinal level. Objective: Serotonin-noradrenaline reuptake inhibitors have been shown to reduce pain in FMS patients possibly through descending monoaminergic pain pathways modulation. This randomized double-blind placebo-controlled trial assessed the pharmacodynamic activity of the dual-reuptake inhibitor milnacipran (MLN) at the spinal level by means of the objective spinal NFR. Study Design: Randomized, double-blind, placebo-controlled trial Setting: A single academic medical center, outpatient setting Methods: Seven-week exposure (100, 150, 200mg/day) in women fibromyalgia patients. Evaluation consisted of extensive quantitative sensory testing including determination of the NFR threshold, selfreported standard questionnaires investigating pain, visual analog scales, fibromyalgia impact, healthrelated quality of life, depression and anxiety questionnaires, as well as the Patient’s Global Impression of Change (PGIC). Analysis of covariance adjusted for baseline value was used for all endpoints. Results: Seventy-seven (39 placebo, 38 milnacipran all doses) out of 80 randomized patients were available for analysis. The absence of influence of MLN (any dose) on the NFR surprisingly contrasted with the dose-dependent analgesic effect observed in MLN-treated patients with an adjusted change difference of -18.4mm (-30.9; -5.8) in pain reduction between placebo and the maximum dosage (200 mg) MLN groups (P = 0.02). Unchanged depression and anxiety scores confirmed the predominant selectivity of the analgesic effect of MLN on nociceptive pain pathway. Self-reported questionnaires consistently reflected the positive effects of MLN on quality of life and psychological well-being. Odds ratio 5.1 for PGIC responders (i.e. much/very much improved) was significantly in favor of MLN (P = 0.04). Conclusion: Milnacipran has a predominantly supraspinal analgesic effect as evidenced by the significant clinical benefits and the absence of changes in the nociceptive spinal reflex threshold. Higher dose was associated with higher pain reduction. Reported analgesia was independent of patients’ emotional status. Key words: Fibromyalgia; chronic pain, spinal nociceptive flexion reflex, milnacipran, dual- reuptake inhibitor, 5-HT noradrenaline re-uptake inhibitor, descending noxious inhibitory controls, quantitative sensory testing, Patient Global Impression of Change, Fibromyalgia Impact Questionnaires

Focused analgesia and generalized relaxation produce differential hypnotic analgesia in response to ascending stimulus intensity

This study was designed in order to examine the effects of different types of hypnotic suggestion on hypnotic analgesia. Generalized relaxation and focused analgesia were induced in seven high-hypnotizable (HH) and eight low-hypnotizable (LH) subjects. Subjects were not aware to which group they belonged. The two groups did not differ in their expectation rates to achieve analgesia under hypnosis. Pain intensity and unpleasantness were rated on visual analogue scales in response to painful electrical stimuli, delivered in random order in five ascending intensities. Both focused analgesia and generalized relaxation decreased pain intensity significantly ( P<0.01). However, stimulus-intensity response curves differed under the two hypnotic conditions. As stimulus intensity became higher pain reduction was enhanced under focused analgesia, while a constant reduction occurred under generalized relaxation. The interaction between hypnotic state and stimulus intensity was significant for focused analgesia ( P<0.05) but not for generalized relaxation ( P>0.07), difference became more pronounced when analyzed for HH subjects only ( P<0.002 for analgesia, P>0.10 for relaxation). Pain reduction was significantly higher in HH than in LH subjects under focused analgesia ( P<0.02) but not under generalized relaxation ( P>0.5). We conclude that by utilizing two modes of hypnotic suggestions in response to ascending stimuli, we were able to discover two components of hypnotic analgesia. One shows a parallel shift in the stimulus–response function, has features similar to placebo and bears no clear relationship to hypnotic susceptibility. The other shows a slope change in the stimulus–response curve and has a positive relationship to hypnotic susceptibility.