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Contributors to the ongoing epidemic of prescription opioid abuse, addiction, and death include opioid tolerance, withdrawal symptoms, and possibly opioid-induced hyperalgesia (OIH). Thirty stable chronic non-malignant pain patients entered a six-month long, randomized, double-blind, dose-response, two-center trial of the potent opioid levorphanol, conducted over a decade ago during an era of permissive opioid prescribing. Eleven were taking no opioids at study entry and eleven were taking between 35-122 morphine equivalents (MEQ). Five weeks titration preceded twenty weeks stable dosing. Tolerance and OIH were inferred individually based on chronic pain ratings, Brief Pain Inventory scores, and results of the Brief Thermal Sensitization (BTS) model at five opioid dosing sessions. Seventeen patients completed. The average final daily opioid dose was 132; range 14-300; average addition 105 MEQ. After observed dosing, the BTS area of hyperalgesia changed minimally but the painfulness of skin heating was reduced. Weekly 0-100 VAS pain ratings (average 64 at study entry, 48 at end titration, 45 at end stable dosing) decreased a median 19%, but eight completed with higher VAS ratings. Three completers had evidence of both tolerance and hyperalgesia. A fully-powered trial similar to this feasibility study is ethically questionable. A large-scale pragmatic trial is more realistic. Trial Registration: NCT00275249 Evolution of Analgesic Tolerance With Opioids Perspective: A double-blind, six-month, high-dose opioid feasibility trial, completed years ago, provides critically important data for clinically defining analgesic tolerance and opioid-induced hyperalgesia (OIH). Overall benefit was small, and 18% of patients had evidence of both tolerance and OIH. Future work requires a different approach than a classic RCT design.
Learn More >Embedded behavioral medicine services are a common component of multidisciplinary chronic pain treatment programs. However, few studies have studied whether these services are associated with improved treatment outcomes.
Learn More >Introduction There is limited evidence for effect of interventional treatment, and pragmatic studies are needed to assess these interventions within a clinical setting. The aim of this study was to describe patients referred to an interventional pain clinic and investigate responses after spinal intervention in general and for radiofrequency ablation (RFA) and transforaminal epidural corticosteroid administration (TECA), specifically. Methods This is a prospective, non-controlled study of patients with chronic spinal pain. The procedures were performed in accordance with the Spine Intervention Society recommendations. Outcome data after a median of 4.5 months are presented, and for those treated with RFA also after 6 and 12 months. Results Among 815 patients, 190 patients underwent diagnostic blocks only and 625 interventional treatment, of these 94 RFA and 246 TECA. Of the whole sample 70% reported pain reduction, for 49% ≥ 50%, while 9% were pain free (p < 0.001). Highest pain intensity decreased from 7.1 to 5.4 [95% Confidence Interval of the Difference (95%-CI): 1.4-1.9] (p < 0.001), while Euroqual – visual analogue scale for general health (EQ-VAS) improved from 48 to 58 (95%-CI: 7.6-11.9) (p < 0.001), and Euroqual-5 Dimensions-5 Levels Index for health related quality of life (EQ-5D-5L Index) from 0.489 to 0.628 (95%-CI: 0.123-0.157) (p < 0.001). The proportions, not taking analgesics, increased from 16% to 30%, and proportion taking strong opioids decreased from 14% to 9% (p < 0.001). We found no significant change in proportion receiving physiotherapy/other treatment nor occupational status. No complications were reported. Among patients treated with RFA, 77% reported pain reduction, for 56% ≥ 50%, while 9% were pain free (p < 0.001). Highest pain intensity decreased from 6.9 to 4.6 (95%-CI: 1.6-3.0) (p < 0.001), while EQ-VAS improved from 47 to 57 (95%-CI: 4.8-13.6 (p < 0.001), and EQ-5D-5L Index from 0.489 to 0.643 (95%-CI: 0.117-0.191) (p < 0.001). The proportion not taking analgesics, increased from 7% to 23% and proportion taking strong opioids decreased from 16% to 10%. Among patients who responded at 6- and 12-month follow up, the proportions reporting pain reduction, EQ-VAS, and EQ-5D-5L Index remained significantly improved from baseline, and the change in proportions taking analgesic and opioids achieved statistical significance. We found no significant change in proportion receiving physiotherapy/other treatment nor occupational status. Among patients treated with TECA, 58% reported pain reduction, for 36% ≥ 50%, while 5% were pain free (p < 0.001). Highest pain intensity decreased from 7.2 to 6.2 (95%-CI 0.5-1.4) (p < 0.001), while EQ-VAS improved from 46 to 52 (95%-CI: 2.0-3.6) (p < 0.001), and EQ-5D-5L Index from 0.456 to 0.571 (95%-CI: 0.077-0.138) (p < 0.001). The proportions, not taking analgesics, increased from 17% to 27% and proportion taking strong opioids decreased from 15% to 10%, but the changes did not reach statistical significance. We found no significant changes in the proportion who recieved physiotherapy/other treatment nor occupational status. Conclusion The study demonstrates substantial short-term responses after spinal intervention and long-lasting improvement for a subsample of the RFA treated patients. We observed larger proportions reporting pain reduction among those treated with cervical RFA. Implementation Quality assessment should be implemented in interventional pain clinics to improve treatment quality.
Learn More >Chronic pain conditions are complicated and challenging to live with. Electronic health (eHealth) interventions show promise in helping people cope with chronic illness, including pain. The success of these interventions depends not only on the technology and intervention content but also on the users' acceptance and adherence. Involving all stakeholders (eg, patients, spouses, health care providers, designers, software developers, and researchers) and exploring their input and preferences in the design and development process is an important step toward developing meaningful interventions and possibly strengthening treatment outcomes.
Learn More >We explore factors that may have contributed to differences in treatment-emergent adverse events in the phase 2 and phase 3 lasmiditan clinical trials.
Learn More >Fibromyalgia (FM) is a chronic syndrome characterised by widespread musculoskeletal pain associated with other symptoms, including psychological distress. While negative mood (anxiety, depression, and anger) has been widely explored in FM, few studies have investigated emotional dysregulation. Our purpose was to evaluate problems in the processes of emotional regulation and to explore their influence on the severity of pain and disability.
Learn More >Altered pain modulation and resting state functional connectivity (rsFC) were found to be related to migraine pathology and clinical manifestation. We examined how pain modulation psychophysical measures are related to resting-state networks (RSNs) and rsFC between bottom-up and top-down pain modulation areas. Thirty-two episodic migraineurs and 23 age-matched healthy individuals underwent temporal summation of pain (TSOP) and conditioned pain modulation (CPM) tests, followed by a resting-state imaging scan. No differences in TSOP and CPM were found between groups. However, in healthy individuals, more efficient CPM was correlated with: 1) stronger rsFCs of the posterior cingulate cortex (PCC), with the ventromedial prefrontal cortex (vmPFC) and with the pregenual anterior cingulate cortex (pgACC); 2) weaker rsFC of the anterior insula with the angular gyrus. However, in migraineurs, the association between CPM and rsFC was altered. Our results suggest that the functional connectivity within the default mode network (DMN) components and the functional coupling between the DMN and pain inhibitory brain areas is linked with pain inhibition efficiency. In migraineurs, this interplay is changed, yet enables normal pain inhibition. Our findings shed light on potential functional adaptation of the DMN and its role in pain inhibition in health and migraine. Perspective: This article establishes evidence for the relationship between the resting-state brain and individual responses in psychophysical pain modulation tests, in both migraine and healthy individuals. The results emphasize the significant role of the default mode network in maintaining pain inhibition efficiency in heath and in the presence of chronic pain.
Learn More >Do measures of state anxiety and trait anxiety in people with acute low back pain (ALBP) improve prediction of chronic low back pain (CLBP), defined as pain or pain-related disability at 12 weeks?
Learn More >In health and disease, the somatosensory system has been interrogated with standardized research techniques, collectively referred to as quantitative sensory testing (QST). In neuropathic pain, QST has been used to characterize multiple sensory derangements. However, the use of QST outside the lab has been limited by several factors, including a lack of standardization, variability in procedural technique, and duration of testing that would be unacceptable for clinic. To address these shortcomings, the Neuropathic Pain Research Consortium (NPRC) designed an easy and low-cost "bedside" QST procedure. To test the hypothesis that this procedure would be clinically reliable over time and across different examiners, a multi-site, blinded study was performed in subjects with postherpetic neuralgia. Generally, agreement between two examiners and over two study visits with one examiner was high. Additionally, intraclass correlation coefficients and Kappa statistics calculated showed that the battery of QST tests included were highly reliable. Interestingly, mechanical modalities (light brush, pinprick, pressure, and vibration) showed the highest reliability. The least reliable modalities were cool (room temperature) and warmth (38°C). These data demonstrate that the NPRC beside QST protocol is reliable across examiner and over time, providing a validated QST tool for use in clinical practice and clinical trials. Perspective: This blinded, multi-center trial in 32 patients with postherpetic neuralgia demonstrates bedside quantitative sensory testing is reliable and suitable as a clinical trial outcome. The novel bedside battery could be used in clinical trials or in clinical practice over time given the reliability data presented in this article.
Learn More >As yet, there is limited research that can identify factors that differentiate between painful and nonpainful neuropathies after traumatic nerve injury. The aim of this study was to compare subjects with pain and without pain, all after operative nerve repair in the upper extremities.
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