Wednesday, January 31, 2018
Monday, January 29, 2018
Medical cannabis: A forward vision for the clinician
Abstract
Medical cannabis has entered mainstream medicine and is here to stay. Propelled by public advocacy, the media and mostly anecdote rather than sound scientific study, patients worldwide are exploring marijuana use for a vast array of medical conditions including management of chronic pain. Contrary to the usual path of drug approval, medical cannabis has bypassed traditional evidence-based study and has been legalized as a therapeutic product by legislative bodies in various countries. While there is a wealth of basic science and preclinical studies demonstrating effects of cannabinoids in neurobiological systems, especially those pertaining to pain and inflammation, clinical study remains limited. Cannabinoids may hold promise for relief of symptoms in a vast array of conditions, but with many questions as yet unanswered. Rigorous study is needed to examine the true evidence for benefits and risks for various conditions and in various patient populations, the specific molecular effects, ideal methods of administration, and interaction with other medications and substances. In the context of prevalent use, there is an urgency to gather pertinent clinical information about the therapeutic effects as well as risks. Even with considerable uncertainties, the health care community must adhere to the guiding principle of clinical care ‘primum non nocere’ and continue to provide empathetic patient care while exercising prudence and caution. The health care community must strongly advocate for sound scientific evidence regarding cannabis as a therapy.
Significance
Legalization of medical cannabis has bypassed usual drug regulatory procedures in jurisdictions worldwide. Pending sound evidence for effect in many conditions, physicians must continue to provide competent empathetic care with attention to harm reduction. A vision to navigate the current challenges of medical cannabis is outlined.
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Comparison of Intra-articular Thoracic Facet Joint Steroid Injection and Thoracic Medial Branch Block for the Management of Thoracic Facet Joint Pain
Study Design. A prospective observational study. Objective. The aim of this study was to show the effect of intra-articular (IA) thoracic facet joint (TFJ) steroid injection for the management of TFJ pain, and to compare it with the effect of therapeutic thoracic medial branch block (MBB) with a local anesthetic and steroid. Summary of Background Data. Several studies have shown the effects of thoracic MBB with local anesthetics with or without steroids and radiofrequency neurotomy in managing TFJ pain, but thus far, the effectiveness of IA TFJ steroid injection has not been studied. Methods. Forty patients with TFJ pain were recruited and randomly assigned to one of two groups, the IA steroid injection and the MBB group, each with 20 patients. For IA TFJ steroid injection and therapeutic MBB, we injected 0.5 mL of 0.5% bupivacaine, mixed with 10 mg (0.25 mL) of dexamethasone. We assessed the severity of TFJ pain using a numeric rating scale (NRS) before treatment and at 1, 3, and 6 months after treatment. Results. Compared to the pretreatment NRS scores, the NRS scores at 1, 3, and 6 months after each treatment showed a significant decrease in patients in both the groups. Intergroup changes in the NRS scores were not significantly different over time. Six months after the treatment, 65% of the patients in the IA steroid injection group reported successful pain relief (pain relief ≥50%), and 40% of the patients in the MBB group showed successful pain relief. Conclusion. In the present study, both IA TFJ steroid injection and therapeutic MBB significantly relieved TFJ pain. Their effects persisted for at least 6 months after the procedure. Thus, we think that both IA TFJ steroid injection and therapeutic thoracic MBB are useful treatment options for managing TFJ pain. Level of Evidence: 2from Spine - Featured Articles - Featured Articles http://ift.tt/2niiLRL
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Does Additional Uncinate Resection Increase Pseudarthrosis Following Anterior Cervical Discectomy and Fusion?
Study Design. Retrospective comparative study. Objective. To investigate whether unilateral or bilateral uncinate resection (UR) combined with anterior cervical discectomy and fusion (ACDF) increases the risk of pseudarthrosis at long-term follow-up. Summary of Background Data. Uncoforaminotomy (or UR), performed along with ACDF, facilitates better and faster improvement of arm pain. As uncovertebral joints are important for maintaining stability, they may affect the fusion process by causing segmental instability if resected during ACDF. Methods. We retrospectively examined 167 patients (89 men, 78 women; mean age, 58.4 ± 10.5 yr) who consecutively underwent single- or double-level ACDF and were followed for >2 years. UR was not performed in 46 patients (N-UR group). UR of at least one foramen was performed in 121 patients (UR group), including unilateral UR in 89 patients (U-UR group) and bilateral UR in 32 patients (B-UR group). Demographic data, fusion rate, visual analog scale (VAS) scores for neck/arm pain, and neck disability index (NDI) scores were compared between the N-UR and UR groups. Moreover, the fusion rates after the single- and double-level procedures were compared among the groups. Results. There was no difference in sex, age, weight, height, body mass index (BMI), and smoking history between the N-UR and UR groups. The fusion rates after single-level ACDF were not significantly different among the N-UR, U-UR, and B-UR groups (91.4%, 97.8%, and 88.2%; P = 0.290). Solid fusion was achieved in all groups after double-level ACDF (72.7%, 95.5%, and 86.7%), although the rates did not significantly differ among the groups (P = 0.071). The improvement in the VAS score for arm pain was significantly better in the UR group than in the N-UR group at short-term follow-up (P < 0.001). Conclusion. Unilateral or bilateral UR does not affect the fusion rate after single- or double-level ACDF. Hence, if necessary, additional UR can be performed during ACDF without concern regarding nonunion. Level of Evidence: 4from Spine - Featured Articles - Featured Articles http://ift.tt/2nijt1n
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Clinical and Radiological Mid-Term Outcomes of Lumbar Single-Level Total Disc Replacement
Study Design. Prospective single-center case cohort study. Objective. Evaluation of clinical and radiographic outcomes of a consecutive 122-patient cohort with discogenic back pain, at 2- to 10-year follow-up periods, treated by a single surgeon, with CHARITÉ Artificial Disc (DePuy Spine, Raynham, MA). Summary of Background Data. Minimum 2-year clinical and radiographic level 1 data for the first lumbar artificial disc, the CHARITÉ Artificial Disc (DePuy Spine), have recently been published, demonstrating sustained clinical benefit of the device for the treatment of degenerative disc disease. Methods. Patients were assessed preoperatively using clinical outcome measures, including visual analog scale (VAS) score back and leg, Oswestry Disability Index (ODI), 36-Item Short Form Health Survey (SF-36), and Roland-Morris Questionnaires (RMDQ), and further assessed postoperatively, 3-, 6-, 12-months, and yearly thereafter. Results. Average follow-up was 44.9 ± 23.3 months (n = 122). The median age at surgery was 43.0 ± 9.0 years. Preoperative diagnosis included degenerative disc disease in 118 (96.7%) and internal disc disruption in 4 (3.3%). Surgery was performed at L5–S1 in 96 (77.9%) patients and at L4–L5 in 27 (22.1%). Statistically significant clinical improvements from baseline were observed on VAS (back and leg), ODI, SF-36 PCS, SF-36 MCS, and RMDQ 3 months onward. Back VAS scores decreased from 78.2 ± 21.3 preoperatively to 21.9 ± 27.8 by final follow-up. ODI scores decreased from 51.1 ± 17.3 to 16.2 ± 17.9 at last follow-up. The RMDQ scores also decreased from 16.7 ± 4.7 to 4.2 ± 5.8. SF-36 PCS and MCS increased from 25.7 ± 11.0 to 46.4 ± 10.3 for PCS and from 35.5 ± 17.4 to 51.6 ± 10.8 for MCS. Patient satisfaction surveys indicated that 90.56% patients rated their satisfaction with the surgery as “excellent” or “good” at 2 years. Range of motion averaged 8.6 ± 3.5 (median = 8.0°) at the last follow-up time point. Conclusion. Outcomes verify the clinical efficacy of total disc replacement for treatment of discogenic back pain with or without radiculopathy. The outcomes instruments demonstrated statistically significant improvements 3 months onward. Level of Evidence: N/Afrom Spine - Featured Articles - Featured Articles http://ift.tt/2BACekO
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Subcrestal Iliac-Screw: A Technical Note Describing a Free Hand, In-line, Low Profile Iliac Screw Insertion Technique to Avoid Side-connector Use and Reduce Implant Complications
Study Design. Case-series. Objective. To report our modified iliac-screw insertion technique and its clinical outcomes. Summary of Background Data. Iliac-screws are one of the preferred methods for modern spinopelvic-fixation. However, the technique is not without complications, predominantly because of iliac-screw head prominence, leading to pain and revisions. Conventional iliac-screw entry point is sited superficially at the posterior-superior-iliac-spine (PSIS) contributing to screw-head prominence. We propose a more low-profile, subcrestal entry point that is more medial and inferior to the PSIS at the medial wall of the iliac crest, lying underneath the crest but above the sacroiliac joint. This position keeps the screw-head low profile and in-line with proximal instrumentation to ease rod engagement. Methods. Ten consecutive patients who underwent spinal deformity correction surgery using the modified iliac-screw entry point fixations were enrolled. Clinical, radiological, and surgical parameters were reviewed. Results. Five males and five females with average age of 66 years and average follow up of 29 months were reviewed. Mean preoperative Cobb angle and C7-SVA were 32.1° and 10.3 cm, respectively. Surgical indication was progressive deformity and neurogenic claudication in eight cases and fracture in two cases. Twenty noncannulated, polyaxial iliac-screws with median dimension of 7.5 x 75 mm were inserted free hand. Bilateral S1 screws were used in all except two cases. Only five out of 16 iliac-screws with concomitant S1 screws needed side-connectors. At the last follow up only one iliac-screw head was felt to be prominent but without pain in a Parkinson's patient. None of the 10 patients had cases of revision, breakages, or sacroiliac pain. Conclusion. Subcrestal iliac-screw insertion is feasible, safe, and has the potential to reduce screw-head complications and avoid the use of side-connectors, lowering construct complexity and cost. The technique has the advantage of both the low-profile S2 alar iliac screw and the ease of free-hand insertion of the traditional iliac-screw. Level of Evidence: 4from Spine - Featured Articles - Featured Articles http://ift.tt/2nidKsh
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Concurrent Use of Lumbar Total Disc Arthroplasty and Anterior Lumbar Interbody Fusion: The Lumbar Hybrid Procedure for the Treatment of Multilevel Symptomatic Degenerative Disc DiseaseA Prospective Study
Study Design. A prospective study. Objective. The aim of this study was to evaluate clinical and patient outcomes post combined total disc arthroplasty (TDA) and anterior lumbar interbody fusion (ALIF), known as hybrid surgery for the treatment of multilevel symptomatic degenerative disc disease (DDD). Summary of Background Data. Class I studies comparing the treatment of one-level lumbar DDD with TDA and ALIF have confirmed the effectiveness of those treatments through clinical and patient outcomes. Although the success of single-level disease is well documented, the evidence relating to the treatment of multilevel DDD with these modalities is emerging. With the evolution of the TDA technology, a combined approach to multilevel disease has developed in the form of the hybrid procedure. Methods. A total of 617 patients underwent hybrid surgery for chronic back pain between July 1998 and February 2012. Visual Analog Pain Scale for the back and leg were recorded along with the Oswestry Disability Index and Roland Morris Disability Questionnaire. Results. Both statistically and clinically significant (p < 0.005) reductions were seen in back and leg pain, which were sustained for at least 8 years postsurgery. In addition, significant improvements (P < 0.001) in self-rated disability and function were also maintained for at least 8 years. Patient satisfaction was rated as good or excellent in >90% of cases. Conclusion. The results of this research indicate that improvements in both back and leg pain and function can be achieved using the hybrid lumbar reconstructive technique. Level of Evidence: 4from Spine - Featured Articles - Featured Articles http://ift.tt/2BCbSiI
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Improvement in Scoliosis Research Society-22R Pain Scores After Surgery for Adolescent Idiopathic Scoliosis
Study Design. Longitudinal cohort. Objective. To investigate whether patients with painful adolescent idiopathic scoliosis experience pain relief with surgical treatment. Summary of Background Data. Adolescent idiopathic scoliosis (AIS) was previously thought to be a painless condition, but recent studies have shown that a significant proportion of patients have pain. Little information is available regarding pain relief with surgical treatment for AIS. Methods. Patients enrolled in a prospective database of surgically treated AIS were divided into two groups based on their preoperative Scoliosis Research Society (SRS)-22R pain domain score. Patients with a preoperative pain domain score of 4 or more (N = 1005) were classified as nonpainful. If the preoperative pain domain score was less than 4 (N = 505), they were classified as painful. Demographics, SRS total and domain scores, and changes with treatment were compared for the two groups. Results. The two groups had similar demographics and preoperative coronal curve magnitude. Patients with painful scoliosis experienced significant improvement in SRS-22R pain scores, from 3.29 preoperatively to 4.03 postoperatively (P < 0.000). Eighty-one percent of these patients reached the minimum clinically important difference threshold (0.20) for improvement in pain score. Painful scoliosis patients also had greater 2-year improvement in total and all domain scores than the nonpainful scoliosis patients (P < 0.000). Absolute values of SRS-22R total and domain scores were all greater at 2 years in the nonpainful group than the painful group. Conclusion. Patients with AIS with substantial back pain can be cautiously counseled to expect significant improvement in pain level with surgical correction of their deformity, even if curve progression is the primary indication for surgery. Although these patients achieve greater improvements in health-related quality of life compared with patients with mild or no pain, 2-year SRS-22R scores were still better in patients with mild or no pain preoperatively. Level of Evidence: 2from Spine - Featured Articles - Featured Articles http://ift.tt/2nfpFr6
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Intrathecal Morphine and Oral Analgesics Provide Safe and Effective Pain Control After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis
Study Design. Retrospective comparative study. Objective. The aim of this study was to demonstrate that intrathecal morphine (ITM) and oral analgesics provide effective pain control after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS), and this protocol has a low complication rate so patients can be admitted to a general care floor. Summary of Background Data. Previous studies have shown that ITM combined with intravenous patient-controlled analgesia or epidural infusion (EPI) provides effective pain control after PSF for AIS. Owing to concerns for respiratory depression, ITM patients were routinely admitted to the intensive care unit (ICU) postoperatively. There are little data on ITM combined with oral analgesics. Methods. We identified AIS patients aged 10 to 17 years who had undergone PSF. Twenty-eight patients who received ITM were matched to 28 patients who received a hydromorphone EPI. The ITM group received oral oxycodone starting at 16 hours postinjection. The EPI group received oxycodone after the epidural catheter was removed on postoperative day 2. Pain scores, adverse events, and length of stay were recorded. Results. A higher number of EPI patients received fentanyl (11 vs. 3, P = 0.014) in the post-anesthesia care unit (PACU). The ITM group had lower pain scores between PACU discharge and midnight (mean 2.9 vs. 4.2, P = 0.034). Pain scores were similar during the remaining postoperative periods. All ITM patients transitioned to oxycodone without intravenous opioids. Time to ambulation (19.9 vs. 26.5 hours, P = 0.010) and Foley catheter removal (21.3 vs. 41.9 hours, P < 0.001) were earlier in the ITM patients. Length of hospital stay was shorter in the ITM group (3.1 vs. 3.5 days, P = 0.043). Adverse events occurred at similar rates in both groups. Conclusion. ITM and oral analgesics provide safe and effective pain control after PSF for AIS. Routine postoperative admission to the ICU is not necessary. Level of Evidence: 3from Spine - Featured Articles - Featured Articles http://ift.tt/2BA9jgT
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Predictors of Recovery After Conservative Treatment of AO-Type A Thoracolumbar Spine Fractures Without Neurological Deficit
Study Design. Prospective, correlational, exploratory, clinical research. Objective. To identify the factors determining a patient's recovery after conservative treatment of compression fractures of the thoracolumbar spine. Summary of Background Data. The reported results of compression fractures are poor. These results are not influenced by the severity of compression, the fracture site, or the residual deformity. Otherwise, the factors that determine a patient's recovery are unknown. Methods. In 48 conservatively treated patients the preinjury versus the 12-month follow-up differences (Δ) in back pain (visual analogue scale for pain), Oswestry disability index (ODI), and the Greenough and Fraser low back outcome scale were prospectively recorded. For these differences and for time lost from work and satisfaction, multiple linear regressions with combinations of 16 factors were performed. Results. At 1 year, patients with an income-insurance were 9% (P = 0.096) more disabled than those without. They reported a 15% less favorable global outcome and 27% less participation. Smokers were 13% (P = 0.010) more disabled and 11% (P = 0.044) less satisfied. With each increase of the AO-fracture type from A1 to A3 the disability was 8% worse. Patients with pre-existent chronic low back pain (CLBP) returned two points (on a visual analogue scale [VAS] pain total of 10) more closely (P = 0.041) to their preinjury pain level than those without but were 21% (P = 0.001) less satisfied. Our model offers an explanation for more than 25% of the variability of ΔODI and of the satisfaction. For sick leave, no significant predictors were found. Conclusion. Smoking and insurance status are the strongest negative predictors for recovery. LBP patients returned more closely to their preinjury back pain level, but were less satisfied. The AO fracture type had a marked influence on disability, the sagittal deformity had not. The time lost from work did not depend on patient or injury-related factors. Level of Evidence: N/Afrom Spine - Featured Articles - Featured Articles http://ift.tt/2BzBZqf
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Validation and Cross-cultural Adaptation of the Korean Version of the Zurich Claudication Questionnaire in Patients With Lumbar Spinal Stenosis
Study Design. Linguistic and psychometric validation of a translated questionnaire. Objective. To validate the Korean version of Zurich claudication questionnaire (ZCQ) both linguistically and psychometrically. Summary of Background Data. The ZCQ is considered as a disease specific and gold standard measure for evaluation of patients with lumbar spinal stenosis (LSS). However, there has been no validated Korean version of the ZCQ. Methods. The ZCQ was translated forward and backward, culturally adapted by 2 independent translators, and approved by an expert committee. The final version of the Korean ZCQ was added to a routine questionnaire including a visual analog pain scale (VAS) for back and leg pain, the Oswestry Disability Index (ODI), and the European Quality of Life-5 dimensions (EQ-5D). Psychometric validation included reliability by internal consistency using Cronbach's alpha, the test-retest reliability using intraclass correlation coefficient (ICC), and concurrent validity by comparing the Korean ZCQ to VAS for back/leg pain, ODI, and EQ-5D using Pearson correlation. Results. A total of 109 patients were included in this study. The test-retest intraclass correlation coefficient (ICC) of the ZCQ was shown to have good reliability for all three domains: the ICCs for symptom, function, and satisfaction domains were 0.79, 0.84, and 0.91, respectively. Internal consistency of the Korean ZCQ for the symptom, function, and satisfaction domains was also excellent (Cronbach α = 0.894, 0.939, and 0.961, respectively). For concurrent validity, all three domains of the Korean ZCQ were significantly correlated with external criteria including VAS for back/leg pain, ODI, and EQ-5D. In the assessment of responsiveness, 21 patients who completed the ZCQ both before and after surgery demonstrated significantly different scores for symptom and disability domains. Conclusion. The validated Korean version of the ZCQ is a transculturally equivalent, reliable, and valid tool for use in assessing symptoms, function, and satisfaction with treatment in patients with LSS. Level of Evidence: 3from Spine - Featured Articles - Featured Articles http://ift.tt/2BBkjuo
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Dipyrone is the preferred non-opioid analgesic for the treatment of acute and chronic pain. A survey of clinical practice in German speaking countries
Abstract
Purpose
Non-opioid analgesics are frequently used for the treatment of acute and chronic pain. Dipyrone is an alternative to NSAIDs and paracetamol, however, data on the frequency of its usage by anaesthesiologists in the perioperative and chronic pain setting are lacking and its adverse reactions are a matter of debate.
Methods
The link to a questionnaire on the use of non-opioid analgesics (NSAIDs, COX2 inhibitors, paracetamol, dipyrone) and the safety of dipyrone in the perioperative and chronic pain setting was mailed to anaesthesiologists and pain physicians.
Results
A total of 2237 responses were analysed. 97.4% of the respondents used non-opioid analgesics for the treatment of acute pain, with 93.8% administering dipyrone, 54.0% NSAIDs, 41.8% COX2-inhibitors and 49.2% paracetamol. Non-opioid analgesics were administered preoperatively by 22.3%, intraoperatively by 86.1% and postoperatively by 73% of the respondents. For chronic pain management, 76.7% of the respondents prescribed oral dipyrone in combination with other non-opioid analgesics. 19.9% used dipyrone as sole non-opioid, whereas 2.9% denied its use. Cases of dipyrone associated agranulocytosis were observed by 3.5% of the respondents of the acute and 1.5% of the chronic pain questionnaire, respectively. The majority of respondents (acute pain: 73.0%, chronic pain 59.3%) performed no blood cell counts to monitor dipyrone therapy. Patients were rarely informed about possible adverse drug reactions.
Conclusions
Dipyrone is the preferred non-opioid analgesic in the perioperative and chronic pain setting. Although cases of agranulocytosis occur, benefits apparently outweigh the risks according to anaesthesiologists. Measures like patient information may improve safety.
This article is protected by copyright. All rights reserved.
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Friday, January 26, 2018
Gene transfer of a naked plasmid (pUDK-HGF) encoding human hepatocyte growth factor attenuates skin/muscle incision and retraction-induced chronic post-surgical pain in rats
Abstract
Background
Chronic post-surgical pain (CPSP) remains a major clinical problem and is often refractory to current treatments. New analgesic medications and strategies for pain relief are needed. Hepatocyte growth factor (HGF) is known to be a multi-functional growth factor and regulates various biological activities.
Methods
We investigated the analgesic effect and underlying mechanism of plasmid pUDK-HGF encoding human HGF gene on CPSP induced by skin/muscle incision and retraction (SMIR) in rats. The possible changes of inflammatory factors, glial cell activation and pain sensitivity after pUDK-HGF administration were investigated by ELISA, western blot and Von Frey tests, respectively.
Results
In behavioural assays, we found that a single intramuscular or intrathecal injection of pUDK-HGF significantly attenuated mechanical hypersensitivity to von Frey stimulation of plantar ipsilateral hind paw after SMIR. Intramuscular injection of pUDK-HGF promoted blood flow and proliferation of satellite cells and inhibited inflammatory cells recruitment, collagen accumulation and expression of pronociceptive factors. Intrathecal injection of pUDK-HGF inhibited activation of spinal glial cells and production of inflammatory mediators induced by SMIR.
Conclusions
pUDK-HGF has a strong analgesic potency and efficacy in CPSP induced by SMIR in rats. This study highlights a new strategy for the treatment of CPSP.
Significance
The CPSP occurs following various surgical procedures and remains a major clinical problem due to the lack of study on the mechanisms of CPSP. Our findings provide the first evidence that pUDK-HGF attenuates SMIR-induced pain behaviuors through peripheral or central mechanisms. The peripheral analgesic effect of pUDK-HGF is associated with promoting tissue repair and inhibiting inflammatory response; furthermore, pUDK-HGF inhibits activation of spinal glial cells and overexpression of inflammatory mediators in spinal cord. Therefore, naked pUDK-HGF may be a potential therapeutic strategy for treatment of CPSP in clinic.
from European Journal of Pain http://ift.tt/2BtKa7L
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Blockade of dopamine D2 receptors disrupts intrahippocampal connectivity and enhances pain-related working memory deficits in neuropathic pain rats
Abstract
Background
Dopamine (DA) is thought to be important to local hippocampal networks integrity during spatial working memory (sWM) processing. Chronic pain may contribute to deficient dopaminergic signalling, which may in turn affect cognition. However, the neural mechanisms that determine this impairment are poorly understood. Here, we evaluated whether the sWM impairment characteristic of animal models of chronic pain is dependent on DA D2 receptor (D2r) activity.
Methods
To address this issue, we implanted multichannel arrays of electrodes in the dorsal and ventral hippocampal CA1 field (dvCA1) of rats and recorded the neuronal activity during a classical delayed food-reinforced T-maze sWM task. Within-subject behavioural performance and patterns of dorsoventral neural activity were assessed before and after the onset of persistent neuropathic pain using the spared nerve injury (SNI) model.
Results
Our results show that the peripheral nerve lesion caused a disruption in sWM and hippocampus spike activity and that disruption was maximized by the systemic administration of the D2r antagonist raclopride. These deficits are strictly correlated with a selective disruption of hippocampal theta-oscillations. Particularly, we found a significant decrease in intrahippocampal CA1 field connectivity level.
Conclusions
Together, these results suggest that disruption of the dopaminergic balance in the intrahippocampal networks may be important for the development of cognitive deficits experienced during painful conditions.
Significance
This study provides new insights into the role of D2r in the manifestation of pain-related sWM deficits. Our findings support that selective blockade of D2r produces a significant decrease in intrahippocampal connectivity mediated by theta-oscillations, and amplifies pain-related sWM deficits. These results suggest that further characterization of intrahippocampal dopaminergic modulation may be clinically relevant for the understanding of cognitive impairments that accompanies nociceptive stressful conditions.
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Reciprocal associations of pain and post-traumatic stress symptoms after whiplash injury: A longitudinal, cross-lagged study
Abstract
Background
The objectives of the current study were to investigate (1) the longitudinal, reciprocal associations between pain and post-traumatic stress symptoms as proposed by the mutual maintenance model, and (2) to assess the predictive value of the three clusters of post-traumatic stress, where the model revealed that post-traumatic stress symptoms maintained pain in a consecutive cohort of whiplash-injured.
Methods
Participants (n = 253; 66.4% women) were people with WAD grades I–III following motor vehicle crashes in Australia. Pain and post-traumatic stress symptoms were assessed by questionnaires over the course of a year (at baseline (<4 weeks), 3, 6 and 12 months post-injury). The objectives were tested using auto-regressive cross-lagged modelling and two additional structural equation models.
Results
The analyses revealed that post-traumatic stress symptoms at baseline predicted an increase in pain between baseline and 3 months and that post-traumatic stress symptoms at 6 months predicted an increase in pain between 6 and 12 months, beyond the stability of pain over time. Furthermore, hyperarousal at baseline significantly predicted pain at 3 months and hyperarousal at 6 months significantly predicted pain at 12 months with 16 and 30% explained variance, respectively.
Conclusions
The results point to a temporal main effect of post-traumatic stress symptoms on pain over and above the stability of pain itself within the first 3 months post-injury and again in the chronic phase from 6 to 12 months with hyperarousal symptoms driving these effects. From 3 to 6 months, there was a slip in the maintenance patterns with no cross-lagged effects.
Significance
Investigating mutual maintenance of pain and PTSS in whiplash, the present study found evidence suggesting a maintaining effect of PTSS on pain within the first 3 months post-injury and from 6 to 12 months driven by hyperarousal, highlighting the importance of addressing PTSS.
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Preclinical characterization of three transient receptor potential vanilloid receptor 1 antagonists for early use in human intradermal microdose analgesic studies
Abstract
Background
The transient receptor potential vanilloid receptor 1 (TRPV1) is a nonselective cation channel involved in the mediation of peripheral pain to the central nervous system. As such, the TRPV1 is an accessible molecular target that lends itself well to the understanding of nociceptive signalling. This study encompasses preclinical investigations of three molecules with the prospect to establish them as suitable analgesic model compounds in human intradermal pain relief studies.
Methods
The inhibitory effectiveness was evaluated by means of in vitro assays, TRPV1 expressing Chinese hamster ovary cells (CHO-K1) and rat dorsal root ganglion cultures in fluorescent imaging plate reader and whole cell patch clamp systems, as well as in vivo by capsaicin-evoked pain-related behavioural response studies in rat. Secondary pharmacology, pharmacokinetics and preclinical safety were also assessed.
Results
In vitro, all three compounds were effective at inhibiting capsaicin-activated TRPV1. The concentration producing 50% inhibition (IC50) determined was in the range of 3–32 nmol/L and 10–501 nmol/L using CHO-K1 and dorsal root ganglion cultures, respectively. In vivo, all compounds showed dose-dependent reduction in capsaicin-evoked pain-related behavioural responses in rat. None of the three compounds displayed any significant activity on any of the secondary targets tested. The compounds were also shown to be safe from a toxicological, drug metabolism and pharmacokinetic perspective, for usage in microgram doses in the human skin.
Conclusion
The investigated model compounds displayed ideal compound characteristics as pharmacological and translational tools to address efficacy on the human native TRPV1 target in human skin in situ.
Significance
This work details the pharmaceutical work-up of three TRPV1-active investigational compounds, to obtain regulatory approval, for subsequent use in humans. This fast and cost-effective preclinical development path may impact research beyond the pain management area, as it allows human target engagement information gathering early in drug development.
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A qualitative analysis of patient-identified adaptive behaviour changes following interdisciplinary Acceptance and Commitment Therapy for chronic pain
Abstract
Background
Interdisciplinary treatment programmes for chronic pain have strong evidence of treatment effect both immediately after treatment and at follow-up. However, despite strong outcome evidence, it is less clear which specific changes in behaviour are most relevant to patients or to outcomes. Indeed, it is not unknown for clinicians and patients to have different views with regard to goals of treatment. This study sought to evaluate the patients’ perspective regarding important behavioural changes that occurred while they were enrolled in a 4-week interdisciplinary programme of Acceptance and Commitment Therapy (ACT) for chronic pain.
Methods
Qualitative data were collected during a treatment session towards the end of treatment. In total, 104 completers from 16 consecutive treatment groups contributed to a data set consisting of 315 unique qualitative comments.
Results
Thematic analysis resulted in a theme hierarchy including overarching themes, midlevel themes and subthemes. Three overarching themes were identified as follows: (1) interacting with self – describing an interplay between various aspects of the individual, (2) activity – concerning how individuals practically and sustainably undertook activities and (3) interacting with others – exploring relationships with other people. The results section further describes the midlevel and subthemes that cluster under the overarching themes.
Conclusions
These data provide initial insights into the patient's perspective of adaptive behavioural changes gained as part of an interdisciplinary programme of chronic pain rehabilitation. Overall, the data suggest the importance of a mix of both ACT-specific and more universal coping/pain rehabilitation elements. Future research may examine how these processes relate more directly to treatment outcome.
Significance
This study provides new qualitative insights into the patient's perspective of adaptive behavioural changes gained as part of interdisciplinary pain rehabilitation. This and future work may help provide a more detailed understanding of the processes and behaviours that result in successful rehabilitation outcomes.
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Thursday, January 25, 2018
Bringing Vioxx back to market
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Comparative pharmacology and toxicology of tramadol and tapentadol
Abstract
Background and Objective
Moderate to severe pain represent a heavy burden in patients’ quality of life, and ultimately in the society and in healthcare costs. The aim of this review was to summarize data on tramadol and tapentadol adverse effects, toxicity, potential advantages and limitations according to the context of clinical use.
Databases and Data Treatment
We compared data on the pharmacological and toxicological profiles of tramadol and tapentadol, after an extensive literature search in the U.S. National Library of Medicine (PubMed).
Results
Tramadol is a prodrug that acts through noradrenaline and serotonin reuptake inhibition, with a weak opioid component added by its metabolite O-desmethyl-metabolite. Tapentadol does not require metabolic activation and acts mainly through noradrenaline reuptake inhibition and has a strong opioid activity. Such features confer tapentadol potential advantages, namely lower serotonergic, dependence and abuse potential, more linear pharmacokinetics, greater gastrointestinal tolerability and applicability in the treatment of chronic and neuropathic pain.
Conclusions
Although more studies are needed to provide clear guidance on the opioid of choice, tapentadol shows some advantages, as it does not require CYP450 system activation and has minimal serotonergic effects. In addition, it leads to less side effects and lower abuse liability. However, in vivo and in vitro studies have shown that tramadol and tapentadol cause similar toxicological damage. In this context, it is important to underline that the choice of opioid should be individually balanced and a tailored decision, based on previous experience and on the patient's profile, type of pain and context of treatment.
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Assessment of efficacy and safety of eslicarbazepine acetate for the treatment of trigeminal neuralgia
Abstract
Background
Antiepileptic drugs are the first line treatment for trigeminal neuralgia (TN). Carbamazepine and oxcarbazepine are the most studied with well-known efficacy. Eslicarbazepine acetate is a third-generation antiepileptic drug that has not previously been evaluated for the treatment of TN. We aim to assess the efficacy, tolerability, and safety of eslicarbazepine for TN.
Design and Methods
Retrospective, open-label, multicentric, intention-to-treat study. We included patients older than 18 years who met the ICHD-3 beta diagnostic criteria for TN. We evaluated the variation of intensity and frequency of pain paroxysms before and after treatment with eslicarbazepine. Secondary objectives assessed were tolerability and safety of eslicarbazepine.
Results
Eighteen patients were included, 15 women, mean age 65.2 years-old, mean follow-up 21.1 months. The mean number of drugs tested before eslicarbazepine was 2; ten patients used eslicarbazepine as monotherapy. After the treatment with ESL, the median of pain intensity improved from 9.5 to 2.5 (p < 0.001) and the median of pain paroxysms frequency improved from 70 episodes per week to 0.37 (p < 0.001). Responder rate was 88.9%; 44.4% became asymptomatic after treatment. 61% of patients presented some adverse event; 4 patients discontinued eslicarbazepine for this reason. Despite this, 16 patients (88.9%) noticed a good subjective tolerance to eslicarbazepine. The retention rate at 6 months was 77.8% and at 12 months 61.1%.
Conclusions
Our study supports the hypothesis that eslicarbazepine acetate is an effective, safe, and well-tolerated treatment for the treatment of TN. Further studies are warranted to corroborate these results.
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Pain and Sensitisation after Total Knee Replacement or Non-Surgical Treatment in Patients with Knee Osteoarthritis: Identifying Potential Predictors of Outcome at 12 Months
Abstract
Background
This study is a secondary analysis of 12-month follow-ups from two parallel, randomised controlled trials (RCT) in painful knee osteoarthritis patients. RCT1: Total knee replacement (TKR) followed by non-surgical treatment compared with non-surgical treatment. RCT2: Non-surgical treatment compared with usual care.
The aims were to investigate 1) possible predictors of treatment outcome after TKR and non-surgical interventions at 12 months, 2) associations between pain intensity and pressure pain thresholds (PPTs) (pain sensitisation) at baseline and after 12 months, and 3) possible gender differences.
Method
Each RCT included 100 patients. Pain intensities, PPTs, and number of painful sites were assessed at baseline and after 12 months.
Results
In all groups pain improved and pain sensitisation decreased. In RCT1, the TKR group had the greatest improvements in pain. In RCT2 the non-surgical group had the greatest improvement, with no between-group differences in PPTs. Lower PPTs at baseline predicted higher pain after TKR. Baseline pain intensity and PPT levels were associated with the number of painful sites. Subjects with the highest pain and lowest PPTs at baseline showed the largest relative improvement in pain and sensitisation but were still experiencing highest absolute pain and lowest PPTs after 12 months (combined cohorts).
Conclusion
Low PPTs at baseline predicted worse pain outcome after TKR, but did not predict outcome after non-surgical interventions. The number of painful sites was weakly associated with pain and PPTs, and the higher pain/lower PPTs, the higher pain/lower PPTs at 12 months with females showing the lowest PPT values.
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Objective assessment of induced acute pain in neonatology with the Newborn Infant Parasympathetic Evaluation (NIPE) index
Abstract
Background
Objective tools are needed to improve pain assessment in newborns. The aim of this study was to assess the correlation between the Newborn Infant Parasympathetic Evaluation (NIPE) index and two pain scales during a painful procedure in premature infants.
Method
Each baby born at least at 26 weeks of gestational age (GA) undergoing a planned painful procedure in the Neonatal Intensive Care Unit (NICU) was eligible. NIPE index, heart rate variability (HRV) indices and Neonatal Acute Pain scale (DAN) were recorded across three periods: the first at rest 5 min before the painful procedure (T1), the second during it (T2), and the third 3 min after the end of it (T3). The Premature Infant Pain Profile-Revised (PIPP-R) pain scale was recorded at T2.
Results
Sixty-four recordings were performed in 29 preterm infants (mean GA=29.9±4.2 weeks). Twenty-eight tachograms were coupled to NIPE for analysis. We did not find a correlation between the NIPE index and DAN and PIPP-R at the pain time T2. Between T1 and T2, heart rate was higher (159±16 vs. 169±12, p<0.001). Considering the linear HRV indices, we did not observe a modification in parasympathetic or sympathetic activity, while for the nonlinear HRV indices (H exponent, Approximate and conditional Entropy) a significant change towards a loss of physiological chaotic cardiac behavior was detected.
Conclusions
The NIPE index seems to be not reliable to assess acute pain in the preterm infant, but other HRV indices could be explored as additional tools next to pain scales in NICUs.
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Wednesday, January 24, 2018
Comment on a paper by Dincklage et al. entitled “Higher doses of intraoperative analgesia are associated with lower levels of persistent pain and less analgesic consumption six months after total hip arthroplasty.”
Abstract
We read with great interest the article of von Dincklage et al. (2017) in a recent issue of the Journal. The authors concluded after investigating 110 patients undergoing primary total hip arthroplasty that greater levels of intraoperative analgesia are associated with lower levels of persistent pain and less analgesic consumption 6 months after total hip arthroplasty.
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Commentary on a paper by Holden et al
Abstract
In this issue you will find a paper by Holden et al.: “Pain during adolescence can be grouped into four pain classes with distinct profiles: a study on a cohort of 2953 adolescents”. (Holden et al., 2018)
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Effects of Higher versus Lower Threat Contexts on Pain-Related Attention Biases: An Eye-Tracking Study
Abstract
Background
Threat is hypothesized to affect the degree to which pain captures attention but little is known about its impact on dynamic courses of attention towards pain. In this eye-tracking study, we evaluated pain-related visual attention biases during image pair presentations in comparatively lower versus higher threat conditions.
Methods
Gaze biases of healthy adults (47 women, 35 men) were assessed during image presentation phases standardized across (1) a modified visual dot probe task featuring painful-neutral (pain) and neutral-neutral-contrast (neutral) image pair blocks (lower threat context) and (2) an impending pain task wherein the same image pair blocks, respectively, cued potentially painful post-offset somatosensory stimuli (higher threat context) and its absence.
Results
Across tasks, participants were more often oriented towards, gazed longer at, and fixated more times on pain images in pain block trials, though trait fear of pain was not related to any gaze biases. Critically, however, participants reported more state fear and displayed significantly fewer initial fixations, longer first and overall gaze durations, and more unique fixations on pain images when image pairs signaled possible post-offset pain stimulation.
Conclusions
Results underscored stronger overall attention maintenance on visual pain cues in a higher threat (impending pain) context.
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Tuesday, January 23, 2018
Predicting drug efficacy in chronic low back pain by quantitative sensory tests
Abstract
Background
Drugs are prescribed for chronic low back pain without knowing in advance whether a patient will respond to them or not. Quantitative sensory tests (QST) can discriminate patients according to sensory phenotype, possibly reflecting underlying mechanisms of pain processing. QST may therefore be a screening tool to identify potential responders to a certain drug. The aim of this study was to investigate whether QST can predict analgesic effects of oxycodone, imipramine and clobazam in chronic low back pain.
Methods
Oxycodone 15 mg (n = 50), imipramine 75 mg (n = 50) and clobazam 20 mg (n = 49) were compared to active placebo tolterodine 1 mg in a randomized, double-blinded, crossover fashion. Electrical, pressure and thermal QST were performed at baseline and after 1 and 2 h. Pain intensity was assessed on a 0–10 numeric rating scale every 30 min for up to 2 h. The ability of baseline QST to predict pain reduction after 2 h was analysed using linear mixed models. Genetic variants of drug-metabolizing enzymes and genes affecting pain sensitivity were examined as covariables.
Results
No predictor of analgesic effect was found for oxycodone and clobazam. Thermal QST was associated with analgesic effect of imipramine: patients more sensitive to heat or cold were more likely to experience an effect of imipramine. Pharmacogenetic variants and pain-related candidate genes were not associated with drug efficacy.
Conclusions
Thermal QST have the potential to predict imipramine effect in chronic low back pain. Oxycodone and clobazam effects could not be predicted by any of the selected QST or genetic variants.
Significance
Predicting drug efficacy in chronic low back pain remains difficult. There is some evidence that patients more sensitive to heat and cold pain respond better to imipramine.
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Ecological Momentary Assessment Methodology in Chronic Pain Research: a Systematic Review.
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A Kappa Opioid Receptor Agonist Blocks Bone Cancer Pain Without Altering Bone Loss, Tumor Size, or Cancer Cell Proliferation in a Mouse Model of Cancer-Induced Bone Pain
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Pain in severe dementia: A comparison of a fine-grained assessment approach to an observational checklist designed for clinical settings
Abstract
Background
Fine-grained observational approaches to pain assessment (e.g. the Facial Action Coding System; FACS) are used to evaluate pain in individuals with and without dementia. These approaches are difficult to utilize in clinical settings as they require specialized training and equipment. Easy-to-use observational approaches (e.g. the Pain Assessment Checklist for Limited Ability to Communicate-II; PACSLAC-II) have been developed for clinical settings. Our goal was to compare a FACS-based fine-grained system to the PACSLAC-II in differentiating painful from non-painful states in older adults with and without dementia.
Method
We video-recorded older long-term care residents with dementia and older adult outpatients without dementia, during a quiet baseline condition and while they took part in a physiotherapy examination designed to identify painful areas. Videos were coded using pain-related behaviours from the FACS and the PACSLAC-II.
Results
Both tools differentiated between painful and non-painful states, but the PACSLAC-II accounted for more variance than the FACS-based approach. Participants with dementia scored higher on the PACSLAC-II than participants without dementia.
Conclusion
The results suggest that easy-to-use observational approaches for clinical settings are valid and that there may not be any clinically important advantages to using more resource-intensive coding approaches based on FACS. We acknowledge, as a limitation of our study, that we used as baseline a quiet condition that did not involve significant patient movement. In contrast, our pain condition involved systematic patient movement. Future research should be aimed at replicating our results using a baseline condition that involves non-painful movements.
Significance
Examining older adults with and without dementia, a brief observational clinical approach was found to be valid and accounted for more variance in differentiating pain-related and non-pain-related states than did a detailed time-consuming fine-grained approach.
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Monday, January 22, 2018
UK women launch legal action against Bayer over Essure sterilisation device
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Clinical course and prognostic factors across different musculoskeletal pain sites: A secondary analysis of individual patient data from randomised clinical trials
Abstract
Background
Previous research has identified similar prognostic factors in patients with musculoskeletal (MSK) conditions regardless of pain presentation, generating opportunities for management based on prognosis rather than specific pain presentation.
Methods
Data from seven RCTs (2,483 participants) evaluating a range of primary care interventions for different MSK pain conditions were used to investigate the course of symptoms and explore similarities and differences in predictors of outcome. The value of pain site for predicting changes in pain and function was investigated and compared with that of age, gender, social class, pain duration, widespread pain, and level of anxiety/depression.
Results
Over the initial three months of follow-up, changes in mean pain intensity reflected an improvement, with little change occurring after this period. Participants with knee pain due to osteoarthritis (OA) showed poorer long-term outcome (mean difference in pain reduction at 12 months -1.85, 95% CI -2.12 to -1.57, compared to low back pain). Increasing age, manual work, longer pain duration, widespread pain, and increasing anxiety/depression scores were significantly associated with poorer outcome regardless of pain site. Testing of interactions showed some variation between pain sites, particularly for knee OA, where age, manual work and pain duration were most strongly associated with outcome.
Conclusions
Despite some differences in prognostic factors for trial participants with knee OA who were older and had more chronic conditions, similarity of outcome predictors across regional MSK pain sites provides evidence to support targeting of treatment based on prognostic factors rather than site of pain.
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Sunday, January 21, 2018
Increased HCN Channel Activity in the Gasserian Ganglion Contributes to Trigeminal Neuropathic Pain
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Friday, January 19, 2018
Resting Functional Connectivity of the Periaqueductal Gray is Associated with Normal Inhibition and Pathological Facilitation in Conditioned Pain Modulation
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Is Nociception Mechanism Altered in Offspring of Morphine- Abstinent Rats?
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Chronic hip pain
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Differential gene expression in trigeminal ganglia of male and female rats following chronic constriction of the infraorbital nerve
Abstract
Background
The mechanisms underlying sex-based differences in pain and analgesia are poorly understood. In this study, we investigated gene expression changes in trigeminal ganglia (TG) of male and female rats exposed to infraorbital nerve chronic constriction injury (IoN-CCI).
Methods
Somatosensory assessments were performed prior to IoN-CCI and at selected time points postsurgery. Selected gene expression changes were examined with real-time quantitative polymerase chain reaction (RT-PCR) in ipsilateral TG at 21 days postsurgery.
Results
Rats exposed to IoN-CCI developed significant mechanical allodynia and hyperalgesia on days 19 and 21 postsurgery. During this period, females developed significantly more allodynia but not hyperalgesia compared to males. At 21 days postsurgery, expression levels of 44 of the 84 investigated pain-related genes in ipsilateral TG were significantly regulated relative to naïve rats in either sex. Csf1 and Cx3cr1 were up-regulated in both sexes, but the magnitude of regulation was significantly higher in females (p = 0.02 and p = 0.001, respectively). Htr1a and Scn9a were down-regulated in both sexes, but the down-regulation was significantly more pronounced in males (p = 0.04 and p = 0.02, respectively). Additionally, Cck, Il1a, Pla2g1b and Tnf genes were significantly regulated in females but not in males, and Chrna4 gene was significantly down-regulated in males but not in females.
Conclusions
Our findings suggest sex-dependent gene regulation in response to nerve injury, which may contribute to sex dimorphism of trigeminal neuropathic pain. Further studies are needed to establish gene expression changes over time and correlate these with hormonal and other physiological parameters in male and female.
Significance
We present novel sex-specific transcriptional regulation in trigeminal ganglia that may contribute to male-/female-based differences in trigeminal neuropathic pain. These findings are expected to open new research horizons, particularly in male versus female targeted therapeutic regimens.
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Short communication: Persistent socio-economic inequality in frequent headache among Danish adolescents from 1991 to 2014
Abstract
Background
The association between socio-economic status (SES) and headache among adolescents is an understudied issue, and no study has examined whether such an association changes over time. The aim was to examine trends in socio-economic inequality in frequent headache among 11- to 15-year-olds in Denmark from 1991 to 2014, using occupational social class (OSC) as indicator of SES.
Methods
The study applies data from the Danish part of the international Health Behaviour in School-aged Children (HBSC) study. HBSC includes nationally representative samples of 11-, 13- and 15-year-olds. This study combines data from seven data survey years from 1991 to 2014, participation rate 88.6%, n = 31,102. We report absolute inequality as per cent difference in frequent headache between high and low OSC and relative inequality as odds ratio for frequent headache by OSC.
Results
In the entire study population, 10.4% reported frequent headache. There was a significant increase in frequent headache from 8.0% in 1991 to 12.9% in 2014, test for trend, p < 0.0001. This increasing trend was significant in all OSCs. The prevalence of frequent headache was significantly higher in low than high OSC, OR = 1.50 (95% CI: 1.34–1.67). This socio-economic inequality in frequent headache was persistent from 1991 to 2014.
Conclusion
There was a significant and persistent socio-economic inequality, i.e. increasing prevalence of frequent headache with decreasing OSC. The association between socio-economic position and headache did not significantly change over time, i.e. the statistical interaction between OSC and survey year was insignificant.
Significance
The prevalence of frequent headache among adolescents increases with decreasing SES. This socio-economic inequality has been persistent among adolescents in Denmark from 1991 to 2014. Clinicians should be aware of this social inequality.
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Increased pain sensitivity in migraine and tension-type headache coexistent with low back pain: A cross-sectional population study
Abstract
Background
Low back pain is common in the general population and in individuals with primary headaches. We assessed the relative frequency of self-reported back pain in persons with and without primary headaches and examined pain sensitivity.
Method
A population of 796 individuals completed a headache interview based on ICHD criteria and provided data of interest in a self-administered questionnaire. Headache cases were classified into chronic (≥15) (CH) or episodic (<15 headache days/month) (EH). A total of 495 had a pericranial total tenderness score (TTS), and 494 had cephalic and extracephalic pressure pain thresholds (PPTs) assessed.
Results
Adjusted for age, gender, education and poor self-rated health, 1-year relative frequency of back pain was higher in individuals with CH (82.5%) and EH (80.1%) compared to no headache group (65.7%). In persons with back pain, TTS was higher in CH, (26.3 ± 12.1) than in EH, (18.5 ± 10.0; p < 0.001) and higher in both groups than in those with no headache, 10.8 ± 8.5 (p < 0.001 and p < 0.001, respectively). In persons with back pain, temporalis PPT were lower in CH, 169.3 ± 57.8, than in EH, 225.2 ± 98.1, and in no headache group, 244.3 ± 105.4 (p = 0.02 and p = 0.01, respectively). In persons with back pain, finger PPT were lower in CH, 237.1 ± 106.7, than in EH, 291.3 ± 141.3, or in no headache group, 304.3 ± 137.4 (p = 0.02 and p < 0.001, respectively).
Conclusion
Back pain is highly frequent in individuals with CH, followed by EH and no headache. In persons with CH, back pain is associated with lower cephalic and extracephalic PPTs suggesting central sensitization may be a substrate or consequence of comorbidity.
Significance
We found that back pain has high relative frequency in individuals with CH followed EH and no headache. Back pain is associated with low cephalic and extracephalic PPTs in individuals with CH. Central sensitization may be a substrate or consequence of this comorbidity of back pain and CH.
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Thursday, January 18, 2018
[Correspondence] A public health approach to opioid addiction in North America – Author's reply
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Wednesday, January 17, 2018
Tuesday, January 16, 2018
Support for US postdocs is growing slowly
Support for US postdocs is growing slowly
Support for US postdocs is growing slowly, Published online: 16 January 2018; doi:10.1038/d41586-018-00559-8
Report from National Postdoctoral Association highlights progress and pain points.from Nature - Issue - nature.com science feeds http://ift.tt/2DfyniP
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Quadratus lumborum block in management of severe pain after uterine artery embolization
Abstract
Background and objectives
The quadratus lumborum (QL) block has been widely used for acute postoperative pain management after numerous surgical procedures including urological, abdominal, gynaecological and orthopaedic surgical procedures. The local anaesthetic spread in this area can provide unilateral sensory block in T6-L2 dermatomes. We performed bilateral quadratus lumborum block for the management of acute pain after the uterine artery embolization (UAE).
Methods
A 43-year-old woman was admitted to the gynaecology department of Mother and Child Hospital, University Medical Center, for uterine artery embolization. Shortly, after successful completion of the UAE procedure, the patient began to complain of severe pain in the lower abdomen rated as a 9 on a verbal analogue scale (VAS) of 0–10. Intravenous tramadol 100 mg was infused over 30 min with minimal reduction in pain. Trimeperidine 20 mg was then infused over 30 min. Pain scores, however, remained 7–8/10 on the VAS. It was therefore decided to place a bilateral single-shot ultrasound-guided quadratus lumborum block.
Results
The procedure was well tolerated and brought notable pain relief. VAS declined from 8/10 to 5/10 after 30 min and to 3/10 at 60 min. Over the ensuing 24 h, VAS pain intensity remained 2–3/10. No further analgesics were necessary.
Conclusion
A randomized control clinical trial is warranted to assess the efficacy of QL blockade and to compare it with other analgesic options in uterine artery embolization. Bilateral quadratus lumborum blockade may be an excellent pain control option after uterine artery embolization.
Significance
Uterine artery embolization is associated with significant postprocedural pain which can prove difficult to manage with opioids. Bilateral quadratus lumborum block may be an excellent pain control option - one that might significantly reduce not only pain, but also the need for opioids and perhaps even the need for hospitalization.
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Signalling transduction events involved in agonist-induced PGE2/EP4 receptor externalization in cultured rat dorsal root ganglion neurons
Abstract
Background
Prostaglandin E2 (PGE2) enriched in inflamed tissues contributes to chronic pain by sensitizing nociceptive dorsal root ganglion (DRG) neurons (nociceptors). Of four PGE2 receptors (EP1–4), EP4 plays a major role in PGE2-induced nociceptor sensitization. We have previously reported that PGE2 or EP4 agonists stimulated EP4 externalization in cultured DRG neurons and this event contributes to nociceptor sensitization. However, the signalling transduction events governing this event remain unknown.
Methods
In this study, using antibody-based externalization assay, we examined EP subtypes and multiple signalling transduction events involved in PGE2-induced EP4 externalization in cultured DRG neurons.
Results
In addition to EP4 agonist, EP2 agonist, to a lesser extent, also induced EP4 externalization while EP1 and EP3 agonists had no effect. The extracellular and intracellular calcium chelators, the inhibitors of CaMKII, cAMP, PKA, PKC, PKCε, PLC, MAPKs, PI3K and Akt suppressed agonist-induced EP4 externalization. The activator of AC, two PKA-specific cAMP analogues and one Epac-specific cAMP analogue also induced EP4 externalization. ELISA showed that double sequential exposures to EP4 agonists induced a greater release of pain peptide CGRP from cultured DRG neurons than a single exposure, an event blocked by the inhibitor of anterograde transport from ER/Golgi complex to cell surface.
Conclusions
Taken together, these data suggest that mobilization of extracellular and intracellular calcium as well as the activation of CaMKII, cAMP/PKA, cAMP/Epac, PKC/PKCε, MAPKs, PI3K-Akt and PLC signalling transduction pathways are involved in agonist-induced EP4 externalization. Agonist-enhanced EP4 externalization increases EP4 cell surface abundance and activity, thus enhancing nociceptor sensitization.
Significance
This study adds mechanistic information regarding signalling transduction events involved in agonist-induced EP4 cell surface trafficking. EP4 and EP2 (to lesser extent) receptors, extra- and intracellular Ca++, CaKMII, cAMP, PKA, PKC, PKCε, PLC, MAPK, PI3K and Akt are involved in this event. Agonist-induced EP4 externalization contributes to enhanced nociceptor sensitization.
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Machine-learned analysis of quantitative sensory testing responses to noxious cold stimulation in healthy subjects
Abstract
Background
Pain in response to noxious cold has a complex molecular background probably involving several types of sensors. A recent observation has been the multimodal distribution of human cold pain thresholds. This study aimed at analysing reproducibility and stability of this observation and further exploration of data patterns supporting a complex background.
Method
Pain thresholds to noxious cold stimuli (range 32–0 °C, tonic: temperature decrease −1 °C/s, phasic: temperature decrease −8 °C/s) were acquired in 148 healthy volunteers. The probability density distribution was analysed using machine-learning derived methods implemented as Gaussian mixture modeling (GMM), emergent self-organizing maps and self-organizing swarms of data agents.
Results
The probability density function of pain responses was trimodal (mean thresholds at 25.9, 18.4 and 8.0 °C for tonic and 24.5, 18.1 and 7.5 °C for phasic stimuli). Subjects' association with Gaussian modes was consistent between both types of stimuli (weighted Cohen's κ = 0.91). Patterns emerging in self-organizing neuronal maps and swarms could be associated with different trends towards decreasing cold pain sensitivity in different Gaussian modes. On self-organizing maps, the third Gaussian mode emerged as particularly distinct.
Conclusion
Thresholds at, roughly, 25 and 18 °C agree with known working temperatures of TRPM8 and TRPA1 ion channels, respectively, and hint at relative local dominance of either channel in respective subjects. Data patterns suggest involvement of further distinct mechanisms in cold pain perception at lower temperatures. Findings support data science approaches to identify biologically plausible hints at complex molecular mechanisms underlying human pain phenotypes.
Significance
Sensitivity to pain is heterogeneous. Data-driven computational research approaches allow the identification of subgroups of subjects with a distinct pattern of sensitivity to cold stimuli. The subgroups are reproducible with different types of noxious cold stimuli. Subgroups show pattern that hints at distinct and inter-individually different types of the underlying molecular background.
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Friday, January 12, 2018
Effect of physical exercise on musculoskeletal pain in multiple body regions among healthcare workers: Secondary analysis of a cluster randomized controlled trial
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Thursday, January 11, 2018
[Perspectives] A literary pain scale
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Monday, January 8, 2018
Clinical classification criteria for nonspecific low back pain: A Delphi-survey of clinical experts
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Experimental Low Back Pain Decreased Trunk Muscle Activity in Currently Asymptomatic Recurrent Low Back Pain Patients during Step Tasks
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A Functional Neuroimaging Study of Expectancy Effects on Pain Response in Patients with Knee Osteoarthritis
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Friday, January 5, 2018
Daily Anxiety and Depressive Symptoms in Couples Coping with Vulvodynia: Associations with Women's Pain, Women's Sexual Function and Both Partners' Sexual Distress
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Thursday, January 4, 2018
Number and Type of Post-Traumatic Stress Disorder (PTSD) Symptom Domains are Associated with Patient-Reported Outcomes in Patients with Chronic Pain
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Inflammatory and Neuropathic Pain From Bench to Bedside: What Went Wrong?
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An uncommon cause of abdominal pain in a young man
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