Differences in Antinociceptive Signaling Mechanisms Following Morphine and Fentanyl Microinjections into the Rat Periaqueductal Gray

Abstract

Background

Morphine and fentanyl are two of the most commonly used opioids to treat pain. Although both opioids produce antinociception by binding to mu‐opioid receptors (MOR), they appear to act via distinct signaling pathways.

Objective

This study will reveal whether differences in morphine and fentanyl antinociception are the result of selective activation of G‐protein signaling and/or selective activation of pre‐ or postsynaptic MORs.

Methods

The contribution of each mechanism to morphine and fentanyl antinociception was assessed by microinjecting drugs to alter G‐protein signaling or block potassium channels linked to pre‐ and post‐synaptic MORs in the ventrolateral periaqueductal gray (PAG) of male Sprague‐Dawley rats.

Results

Both morphine and fentanyl produced a dose dependent antinociception when microinjected into the PAG. Enhancement of intracellular G‐protein signaling by microinjection of the Regulator of G‐protein Signaling 4 (RGS4) antagonist CCG‐63802 into the PAG enhanced the antinociceptive potency of morphine, but not fentanyl. Microinjection of α‐dendrotoxin into the PAG to block MOR activation of presynaptic K_v ⁺ channels caused a significant rightward shift in the dose‐response curve of both morphine and fentanyl. Microinjection of tertiapin‐Q to block MOR activation of post‐synaptic GIRK channels caused a larger shift in the dose‐response curve for fentanyl than morphine antinociception.

Conclusions

These findings reveal different PAG signaling mechanisms for morphine and fentanyl antinociception. In contrast to fentanyl, the antinociceptive effects of morphine are mediated by G‐protein signaling primarily activated by presynaptic MORs.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/34LScbz
via IFTTT

Comparison of efficacy of diclofenac and tramadol in relieving pain in patients of acute pancreatitis: A randomized parallel group double blind active controlled pilot study

Abstract

Background

Opioids and NSAIDs are commonly used for pain relief in AP. Opioids carry risk of sphincter of oddi constriction. Although diclofenac prevents post ERCP pancreatitis, few reports of diclofenac associated AP is also present. Although, both tramadol and diclofenac are commonly used for pain relief in AP, no study has evaluated their comparative efficacy and safety.

Materials and methods

46 eligible participants were randomized to either diclofenac or tramadol. Primary objectives our study were improvement in pain intensity (VAS pain score after 1 hr of drug administration), number of patients requiring supplementary analgesia. Secondary objectives were total number of times of supplementary analgesia requirement, time to significant decrease (33%) in VAS pain score from baseline, number of painful days (VAS pain score > 5), VAS pain score on 7th day, side effects, all cause death and complications of pancreatitis between the two groups.

Results

Although46 patients were randomized, the final analysis included 41 participants. 5 patients were withdrawn from the study (intubation = 3, altered sensorium = 2). No significant difference was seem in terms of VAS score after 1 hr of drug administration, number of patients requiring supplementary analgesic, number of painful days. However, time taken to significant reduction of pain was lower in the diclofenac group (p = .028). Both the agents were comparable in terms of safety. Although complications were less in the diclofenac group, the difference was not statistically significant.

Conclusion

Both diclofenac and tramadol are equally effective in controlling pain in AP with similar safety profile.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/2R6RS2W
via IFTTT

Bottom‐up or top‐down? The role of child and parent chronic pain and anxiety in the context of parental catastrophizing and solicitousness

Abstract

Children of parents with chronic pain are a high‐risk group to develop own chronic pain. There is evidence that parental responses such as catastrophizing and solicitousness play an important role in the familial transmission of chronic pain. However, little is known about factors that modulate these responses. Based on the literature, we assumed that top‐down processes, such as parent chronic pain and anxiety, would be associated with increased catastrophizing and solicitousness. Bottom‐up processes, such as child chronic pain and anxiety, were assumed to moderate this association.

N = 118 parents (mean age: 43 years, 80.5% females) with chronic pain and/or anxiety symptoms with N = 190 children (mean age: 11 years, 49% females) were recruited in specialized hospitals and via online panels. Parents reported chronic pain, anxiety, catastrophizing, and solicitousness by use of validated questionnaires. Child pain and anxiety were assessed via parent report.

Multilevel model results showed that top‐down processes, rather than bottom‐up processes, predicted parental responses to child's pain. Specifically, parents with more severe chronic pain reported less catastrophizing. Parent anxiety was positively associated with parental catastrophizing and solicitousness. While child chronic pain and anxiety did not exert an impact on parental responses, the parents’ and child's age emerged as additional modulating factors for parental solicitousness.

Findings support the assumption that top‐down processes, particularly parent anxiety, rather than bottom‐up processes, exert an impact on parental responses. Specific interventions to decrease parent anxiety in the context of chronic pain and effects of adult treatment on parental responses to child's pain warrant further investigation.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/2OwnSMf
via IFTTT

What does “moderate pain” mean? Subgroups holding different conceptions of rating scales evaluate experimental pain differently

Abstract

Background

Pain ratings are almost ubiquitous in pain assessment, but their variability is high. Low correlations of continuous/numerical rating scales with categorical scales suggest that individuals associate different sensations with the same number on a scale, jeopardizing the interpretation of statistical results. We analyzed individual conceptions of rating scales and whether these conceptions can be utilized in the analysis of ratings of experimental stimuli in pain‐free healthy individuals and people with reoccurring/persistent pain.

Methods

Using a free positioning task, healthy participants (N = 57) and people with reoccurring/persistent pain (N = 57) ad libitum positioned pain descriptors on lines representing intensity and un‐/pleasantness scales. Further, participants rated experimental thermal stimuli on visual analogue scales with the same end anchors. A latent class regression approach was used to detect subgroups with different response patterns in the free positioning task, indicating different conceptions of pain labels, and tested whether these subgroups differed in their ratings of experimental stimuli.

Results

Subgroups representing different conceptions of pain labels could be described for the intensity and the un‐/pleasantness scale with in part opposing response patterns in the free positioning task. Response patterns did not differ between people with and without pain, but in people with pain subgroups showed differential ratings of high intensity experimental stimuli.

Conclusions

Individuals’ conceptions of pain labels differ. These conceptions can be quantified and utilized to improve the analysis of ratings of experimental stimuli. Identifying subgroups with different conceptions of pain descriptions could be used to improve predictions of responses to pain in clinical contexts.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/2OXoTff
via IFTTT

The treatment of osteoporotic thoraco‐lumbar burst fractures by unilateral percutaneous kyphoplasty：a prospective observation study

Abstract

Objective

Osteoporotic thoraco‐lumbar burst fractures with serious pain are very common, and the optimal treatment of burst fractures without any neurological deficits has not yet been properly codified. The objective of this study was to evaluate prospectively the clinical effects and pain relief of unilateral percutaneous kyphoplasty (PKP) on osteoporotic thoraco‐lumbar burst fractures.

Methods

46 patients with osteoporotic thoraco‐lumbar burst fractures were treated by PKP in our hospital from January 2016 to January 2017. The height of posterior wall (HPW), the height of anterior wall (HAW)and kyphotic angle (KA) were measured via x‐ray radiographs before surgery, one day after surgery and at final follow‐up. Visual analogue scale (VAS) score and the oswestry disability index (ODI) score were evaluated preoperatively, post‐operatively and at final follow‐up. All the patients with osteoporotic thoraco‐lumbar burst fractures were treated by unilateral PKP. Radiological evaluation (anteroposterior and lateral x‐ray radiographs and CT) were performed.

Results

All patients were followed up, and the mean follow up was 28.8 ± 7.0 months. The preoperative HAW was 20.1 ± 2.3 mm, and the HAW was significantly improved to 22.9 ± 2.4 mm after operation (p < .05), and at the final follow up, the HAW was 19.9 ± 2.1 mm, which was lower than the post‐operative HAW. The HPW was also significantly corrected after surgery (p < .05). There were no significant differences between postoperative HPW and the HPW at the final follow up(p > .05). The KA was significantly corrected after operation(p < .05), but relapse occurred at the final follow‐up, and at the final follow‐up, the average of KA was 19.4 ± 1.6 degree. The VAS and ODI were significantly improved at the final follow up compared to the preoperative period (p < .05). Cement leakage was found in 8 patients, and adjacent vertebral fracture was found in 2 patients.

Conclusions

Our present results showed that unilateral PKP acquired satisfactory treatments effect and pain relief in the management of osteoporotic thoraco‐lumbar burst fractures. Meticulous evaluation of preoperative images and careful repetitious injection of cement are important to prevent the cement leakage.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/35RPnpv
via IFTTT

ZNRD1‐AS and RP11‐819C21.1 long non‐coding RNA changes following painful laser stimulation correlate with laser‐evoked potential amplitude and habituation in healthy subjects: A pilot study

Abstract

Long non‐coding RNAs (lncRNAs) are a group of non‐coding RNAs that act as regulators of gene expression; they are implicated in various human diseases and have been reported to be involved in the modulation of pain. We aimed to study whether: 1) lncRNAs modifications could be found in an experimental model of pain and 2) there was a correlation between lncRNA changes and laser evoked potential (LEP) amplitude/laser‐pain rating.

LEPs were recorded from 11 healthy subjects to both left hand and perioral region stimulation. Three consecutive averages were calculated for each stimulation site in order to investigate the LEP amplitude habituation. Blood samples were obtained immediately before LEP recording (pre‐pain) and 30‐min after the recording of the last LEP average (post‐pain). Eighty‐four lncRNAs, involved in autoimmunity and human inflammatory response, were screened. The criteria used for lncRNAs analysis were fold change > 2 and p < .05.

By Real‐Time PCR, we identified 2 lncRNAs up‐regulated at the post‐pain time, as compared to thepre‐pain time: RP11‐819C21.1 (fold change = 8.2; p = .038) and ZNRD1 antisense RNA 1 non‐protein coding (ZNRD1‐AS) (fold change = 6.3; p = .037). The ZNRD1‐AS up‐regulation was directly correlated with the N1 amplitude, while the RP11‐819C21.1 increase after pain showed a correlation with the reduced N2/P2 amplitude and laser‐pain habituation.

This is the first study showing lncRNA changes in a human experimental phasic pain model. The correlation between lncRNA changes and LEP amplitude and habituation suggests that RP11‐819C21.1 and ZNRD1‐AS could be involved in the pathophysiology of painful diseases characterized by abnormal excitability of the cerebral cortex.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/2XVY53c
via IFTTT

Rethinking “long term” opioid therapy

Long term opioid therapy for non-cancer pain has been much debated because of concerns that the harms may outweigh benefits. What has received less attention is how long term should be defined and...

from Latest headlines from BMJ https://ift.tt/2XZnPvi
via IFTTT

[Perspectives] Liz Grant: prioritising palliative care and planetary health

At a rural hospital in Kenya in the late 1990s, Liz Grant saw diseases like cancer and HIV/AIDS destroy lives. “Patients were dying in severe pain, chewing paracetamol—there wasn't sufficient morphine…The voice of one woman still lives with me: ‘I want to go to sleep and wake up dead’”, says Grant, who has worked tirelessly ever since to improve access to palliative care in low-income and middle-income countries (LMICs). The low priority given to end-of-life care means “it has been an uphill struggle”, says Grant, Assistant Principal and Professor of Global Health and Director of the Global Health Academy at the UK's University of Edinburgh.

from The Lancet https://ift.tt/2OXc7NK
via IFTTT

[Clinical Picture] Now you see it: progressive radiographic findings in avascular necrosis of the hip

A 68-year-old woman presented to our hospital with pain in her left hip. She said it had started 2 weeks previously and had gradually worsened. She gave no history of trauma; however, she did have a history of rheumatoid arthritis, which was well controlled with weekly injections of methotrexate. There was no history of corticosteroid use. She also had a history of squamous cell carcinoma of the anus, which had been treated with chemotherapy. The woman had finished a course of adjuvant external beam pelvic radiotherapy 6 months before seeing us.

from The Lancet https://ift.tt/2R00RD6
via IFTTT

IFNβ treatment inhibits nerve injury-induced mechanical allodynia and MAPK signaling by activating ISG15 in mouse spinal cord

Interferons (IFNs) are a class of cytokines originally detected in immunological cells, but have since been shown to be produced during non-immunological responses of both central and peripheral origins. IFNs regulate antiviral and immunomodulatory responses as well as cell growth in immune cells (lymphocytes and macrophages) and non-immune target cells from epithelial and nervous tissues.10,12,34,61,62 There are two major types of IFNs: type I consists chiefly of IFNα and IFNβ, and also IFNω, IFNδ, and IFNτ, whereas type II consists of a single type, IFNγ.

from The Journal of Pain https://ift.tt/37IYVF2
via IFTTT

Investigation of the Involvement of the Endocannabinoid System in TENS-induced Antinociception

Pain is a complex and subjective symptom that involves quantitative and qualitative factors that directly interfere with public health and incurs an economic cost for its control.39 Pharmacological treatment is currently the most used method for controlling pain; however, it produces many side effects and is highly expensive.43 In this context, nonpharmacological treatments, such as transcutaneous electrical nerve stimulation (TENS), have been increasingly used for the treatment of various types of pain, including cancer pain.

from The Journal of Pain https://ift.tt/34sisaC
via IFTTT

Between placebo and nocebo: Response to control treatment is mediated by amygdala activity and connectivity response to control treatment is mediated by amygdala activity and connectivity

Abstract

In experimental placebo and nocebo studies, neutral control treatments are often administered for comparison with active treatments, but are of little interest, as, on average, they result in little change. Yet, when considered at an individual level, they fluctuate between baseline and subsequent measurements and may reveal important information about participants’ placebo/nocebo responding tendencies.

In a paradigm involving application of creams paired with positive, negative and neutral expectations, some subjects rated identical stimuli in the neutral condition as more painful while others as less painful after treatment with inert cream. We divided subjects into two groups based on the median split in these pre‐post responses in the neutral control condition, and investigated 1) fMRI signal differences (post minus pre) between the two groups in neutral condition, and 2) seed‐based resting state connectivity of the bilateral amygdala, known to be involved in emotional self‐regulation, as well as ambiguous stimulus processing and aversive learning.

The results suggested that subjects who rated the same pain stimuli after treatment with explicitly neutral cream as more painful showed stronger fMRI activation of the amygdala during the experiment and had higher connectivity between the left amygdala and the striatum at rest. Neutral pre‐post changes predicted behavioral placebo/nocebo response in this and 2 independent datasets. These findings suggest that measuring pre‐post change in the neutral control condition might provide important information about subjects’ individual differences in placebo/nocebo response.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/33mY6y4
via IFTTT

Is there evidence of efficacy of nonpharmacological interventions in the acute pain management during the laser retinal photocoagulation of patients with diabetic retinopathy?

Abstract

Complications of diabetes mellitus (DM) have had an important impact on public health; in particular, diabetic retinopathy (DR), which can cause blindness and visual impairment, has an annual incidence ranging from 2.2% to 12.7% (Sabanayagam et al., 2018). Laser retinal photocoagulation (LRP) is the first‐line treatment for DR (Evans et al., 2014). Despite the use of anaesthetic eye drops, pain intolerance during LRP may compromise its efficacy by impacting patient adherence to treatment. A study by Chen et al. (2012) revealed that music may be useful for reducing anxiety but not pain during treatment with intravitreal injection (Chen et al., 2012).

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/35yl1I8
via IFTTT

Effects of spicy stimulation and spicy-food consumption on human pain sensitivity: A healthy volunteer study

Spice, one of the most popular food additives, has long been used for flavoring, and coloring of food in countries around the world. In China, spicy foods are the most popular nationwide.41 Spicy foods such as chili peppers have antibacterial properties5,26 and can reduce the risk of obesity43,44 and cancer.1,29 Two recent large population-based prospective studies found an inverse relationship between spicy-food consumption and mortality from all causes, cancer, and respiratory and cardiovascular diseases.

from The Journal of Pain https://ift.tt/37DKBNS
via IFTTT

Lower SRS Mental Health Scores are Associated With Greater Preoperative Pain in Patients With Adolescent Idiopathic Scoliosis

Study Design. Retrospective review of a prospectively collected multicenter database. Objective. The aim of this study was to investigate factors associated with low preoperative SRS pain scores. Summary of Background Data. The prevalence of preoperative pain in patients with adolescent idiopathic scoliosis (AIS) has become increasingly evident and is a primary concern for patients and families. Greater preoperative pain is associated with more postoperative pain; however, less is understood about what contributes to preoperative pain. Methods. A prospectively collected, multicenter database was queried for patients with AIS. Patients were divided into 2 cohorts based on preoperative SRS pain scores: ≤ 3 (Pain cohort), 4 to 5 (No Pain cohort). Univariate analysis was performed identifying which factors were associated with a low preoperative SRS score and used for a CART analysis. Results. Of 2585 patients total, 2141 (83%) patients had SRS pain scores of 4 to 5 (No Pain) and 444 (17%) had SRS pain scores ≤3 (Pain). Female sex, older age, greater % body mass index, larger lumbar curves, greater T5–12 kyphosis, and lower mental health scores were associated with greater preoperative pain. In multivariate CART analysis, lower mental health SRS scores (P = 0.04) and older age (P = 0.003) remained significant, with mental health scores having the greatest contribution. In subdividing the mental health component questions, anxiety-related questions appeared to have the greatest effect followed by mood/depression (SRS Question 13: OR 2.04; Q16: OR 1.35; Q7: OR 1.31; Q3: OR 1.20). Conclusion. Anxiety and mood are potentially modifiable risk factors that have the greatest impact on pre- and postoperative pain. These results can be used to identify higher-risk patients and develop preoperative therapeutic protocols to improve postoperative outcomes. Level of Evidence: 3

from Spine - Featured Articles - Featured Articles https://ift.tt/2KQjENf
via IFTTT

Validation of the Disabilities of the Arm, Shoulder, and Hand in Patients Undergoing Cervical Spine Surgery

Study Design. Retrospective cohort study. Objective. To evaluate the performance and convergent validity of the disabilities of the arm, shoulder, and hand (DASH) in comparison with the visual analog scale (VAS) for pain, and neck disability index (NDI) in patients undergoing cervical spine surgery. Summary of Background Data. Neck-specific disability scales do not adequately assess concurrent upper extremity involvement in patients with cervical spine disorders. The DASH is a patient-reported outcomes (PRO) instrument designed to measure functional disability due to upper extremity conditions but has additionally been shown to perform well in patients with neck disorders. Methods. We identified patients who underwent cervical spine surgery at our institution between 2013 and 2016. We collected demographic information, clinical characteristics, and PRO measures—DASH, VAS, NDI—preoperatively, as well as early and late postoperatively. We calculated descriptive statistics and changes from baseline in PROs. Correlation coefficients were used to quantify the association between PRO measures. The analysis was stratified by radiculopathy and myelopathy diagnoses. Results. A total of 1046 patients (52.8% male) with PROs data at baseline were included in the analysis. The mean age at surgery ± SD was 57.2 ± 11.3 years, and postoperative follow-up duration 12.7 ± 10.7 months. The most common surgical procedure was anterior cervical discectomy and fusion (71.1%). Patients experienced clinically meaningful postoperative improvements in all PRO measures. The DASH showed moderate positive correlations with VAS preoperatively (Spearman rho = 0.43), as well as early (rho = 0.48) and late postoperatively (rho = 0.60). DASH and NDI scores were strongly positively correlated across operative states (Preoperative rho = 0.74, Early Postoperative rho = 0.78, Late Postoperative rho = 0.82). Stratified analysis by preoperative diagnosis showed similar within-groups trends and pairwise correlations. However, radiculopathy patients experienced larger magnitude early and late change scores. Conclusion. The DASH is a valid and responsive PRO measure to evaluate disabling upper extremity involvement in patients undergoing cervical spine surgery. Level of Evidence: 3

from Spine - Featured Articles - Featured Articles https://ift.tt/2Dag1gW
via IFTTT

Complications with Minimally Invasive Transforaminal Lumbar Interbody Fusion for Degenerative Spondylolisthesis in the Obese Population

Study Design. A level-3 retrospective cohort analysis. Objective. The aim of this study was to describe obesity's effect on complications and outcomes in degenerative spondylolisthesis patients treated by minimally invasive transforaminal lumbar interbody fusion (MI TLIF). Summary of Background Data. Obesity is associated with a greater complication rate among lumbar spine surgery patients. Poor clinical outcomes might likewise be supposed, but the association is not well established. Minimally invasive techniques have been developed to reduce complications and improve clinical outcomes in comparison to traditional open techniques. Methods. We reviewed 134 consecutive patients with degenerative spondylolisthesis undergoing MI TLIF. Subjects were grouped into nonobese (N = 65) and obese (N = 69) cohorts. The obese group was further subdivided by BMI. Patient demographics, perioperative complications, and outcome scores were collected over a minimum of 24 months. Four periods (intraoperative, postoperative hospitalization, 6-month, and 24-month postoperative) were assessed. Results. Cohort demographics were not significantly different, but it was noted that obese patients had more major comorbidities than nonobese patients. There was no difference in intraoperative complications between the two groups. The in-hospital complication rate was significantly greater in the obese group. The 6-month postoperative complication rate was not different between cohorts. Wound drainage was most common and noted only in the obese cohort. Complications at 24 months were not different but did trend toward significance in the obese for recurrence of symptoms and total complications. Functional outcome was better among nonobese subjects compared with obese subjects at every interval (significant at 6 and 12 months). Back pain scores were significantly better among nonobese subjects than obese subjects at 24 months, but Leg Pain scores were not different. Conclusions. MI TLIF can be safely performed in the obese population despite a higher in-hospital complication rate. Knowledge of common complications will help the treatment team appropriately manage obese patients with degenerative spondylolisthesis. Level of Evidence: 3

from Spine - Featured Articles - Featured Articles https://ift.tt/2XLoOz7
via IFTTT

Delivery Methods and Dosage of Pain Neuroscience Education, Cognitive Behavioral Therapy, and Mindfulness

Publication date: December 2019

Source: Archives of Physical Medicine and Rehabilitation, Volume 100, Issue 12

Author(s): Lisa Spiker, Zachary Walston, Patricia Pruszynski, Matthew Wronsky, Alex Lettner

from ScienceDirect Publication: Archives of Physical Medicine and Rehabilitation https://ift.tt/2KKWsjy
via IFTTT

A Scoping Review of Falls and Physical Activity among Community-Dwelling Older Adults with Pain

Publication date: December 2019

Source: Archives of Physical Medicine and Rehabilitation, Volume 100, Issue 12

Author(s): Libbey Bowen, Mari Griffioen

from ScienceDirect Publication: Archives of Physical Medicine and Rehabilitation https://ift.tt/2OH4riH
via IFTTT

[Clinical Picture] Seeing red degeneration in uterine fibroids in pregnancy: proceed with caution

A 32-year-old pregnant woman was admitted to our hospital at 18 weeks of gestation with a 5-day history of severe, sharp, and constant abdominal pain. She had no significant medical history and prior to this pain, the pregnancy had been uneventful. On admission, the woman looked pale and was in severe discomfort. Her vital signs were normal. At physical examination we found tenderness in the right lower quadrant of her abdomen but no peritonism. The gravid uterus was soft with a palpable mass at the fundus: there was no vaginal bleeding.

from The Lancet https://ift.tt/33ca1Pc
via IFTTT

Integrated behavioral treatment for Veterans with co-morbid chronic pain and hazardous opioid use: A randomized controlled pilot trial

Chronic pain, defined as pain that persists longer than three months, is common, costly, and debilitating.10,26,35,50 The preponderance of the available evidence suggests that problems associated with chronic pain have been exacerbated by exponential increases in prescribed opioids over the past few decades.3,4 Overall opioid prescription rates have doubled in this century, from 11% to 20% of all pain-related ambulatory and office-based medical visits, while overall rates of pain as a primary symptom and prescription rates of non-opioid analgesics remained unchanged.

from The Journal of Pain https://ift.tt/37qJuRB
via IFTTT

Investigating the Influence and a Potential Mechanism of Self-compassion on Experimental Pain: Evidence from a Compassionate Self-talk Protocol and Heart Rate Variability

Self-compassion is conceptualized as the ability to be kind and caring toward oneself in times of suffering, failure, or perceived inadequacy.35,36 A number of studies have demonstrated the role of self-compassion in protecting emotional well-being against negative life events.3,4,30-32,52,57 In the field of pain research, increasing evidence has identified a positive association between self-compassion and emotional well-being in people with chronic pain,5,15,20,46,56 while the effects of self-compassion on pain perception are mixed.

from The Journal of Pain https://ift.tt/349AkqJ
via IFTTT

A pain in the neck

A 39 year old woman presented with a one week history of progressive swelling and pain on the right side of her neck that was aggravated by eating. She had no relevant dental history. She was...

from Latest headlines from BMJ https://ift.tt/2D4jLQV
via IFTTT

Perioperative intravenous low‐dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo‐controlled study

Abstract

Background

Chronic pain after major lower back surgery is frequent. We investigated in adults the effect of perioperative low‐dose ketamine on neuropathic lower back pain, assessed by the DN4 questionnaire, six and 12 months after major lower back surgery.

Methods

In this single‐centre randomized trial, 80 patients received intravenous ketamine 0.25 mg/kg preoperatively, followed by 0.25 mg/kg hr^‐1 intraoperatively, and 0.1 mg/kg hr^‐1 from 1 hr before the end of surgery until the end of recovery room stay; 80 controls received placebo.

Results

Preoperatively, 47.4% of patients in the ketamine group and 46.3% in the placebo group had neuropathic pain; 10% and 3.8%, respectively, were using strong opioids. At the end of the infusion, the median cumulative dose of ketamine was 84.8 mg (IQR 67.4–106.7) and the median plasma level was 97 ng/ml (IQR 77.9–128.0). At six months, 28.8% of patients in the ketamine group and 23.5% in the placebo group had neuropathic pain (absolute difference, 5.2%; 95% CI −10.7 to 21.1; p = .607). At 12 months, 26.4% of patients in the ketamine group and 17.9% in the placebo group had neuropathic pain (absolute difference 8.5%; 95% CI −6.7 to 23.6; p = .319).

Conclusions

In this patient population with a high prevalence of neuropathic lower back pain undergoing major lower back surgery, a perioperative intravenous low‐dose ketamine infusion did not have an effect on the prevalence of neuropathic lower back pain at six or 12 months postoperatively.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/331z47t
via IFTTT

Diagnosis and treatment of sciatica

What you need to knowSciatica is a clinical diagnosis based on symptoms of radiating pain in one leg with or without associated neurological deficits on examinationMost patients improve over time...

from Latest headlines from BMJ https://ift.tt/2CVvqkX
via IFTTT

Refractory dependence on opioid analgesics

Refractory dependence on opioid analgesics

from PAIN - Featured Articles - Current Issue Highlights https://ift.tt/2rUT3I9
via IFTTT

Epidermal expression of human TRPM8, but not of TRPA1 ion channels, is associated with sensory responses to local skin cooling

Human cold perception and nociception play an important role in persisting pain. However, species differences in the target temperature of thermosensitive ion channels expressed in peripheral nerve endings have fueled discussions about the mechanism of cold nociception in humans. Most frequently implicated thermosensors are members of the transient receptor potential (TRP) ion channel family TRPM8 and TRPA1. Regularly observed, distinct cold pain phenotype groups suggested the existence of interindividually differing molecular bases. In 28 subjects displaying either high or medium sensitivity to local cooling of the skin, the density at epidermal nerve fibers of TRPM8, but not that of TRPA1 expression, correlated significantly with the cold pain threshold. Moreover, reproducible grouping of the subjects, based on high or medium sensitivity to cooling, was reflected in an analogous grouping based on high or low TRPM8 expression at epidermal nerve fibers. The distribution of TRPM8 expression in epidermal nerve fibers provided an explanation for the previously observed (bi)modal distribution of human cold pain thresholds which was reproduced in this study. In the light of current controversies on the role of human TRPA1 ion channels in cold pain perception, the present observations demonstrating a lack of association of TRPA1 channel expression with cold sensitivity–related measures reinforce doubts about involvement of this channel in cold pain in humans. Since TRP inhibitors targeting TRPM8 and TRPA1 are currently entering clinical phases of drug development, the existence of known species differences, in particular in the function of TRPA1, emphasizes the increasing importance of new methods to directly approach the roles of TRPs in humans.

from PAIN - Featured Articles - Current Issue Highlights https://ift.tt/2XrXyFL
via IFTTT

Fatty acid suppression of glial activation prevents central neuropathic pain after spinal cord injury

About half of patients with spinal cord injury (SCI) develop debilitating central neuropathic pain (CNP), with no effective treatments. Thus, effective, safe, and novel therapies are needed urgently. Previously, docosahexaenoic acid (DHA) was reported to confer neuroprotection in preclinical SCI models. However, its therapeutic potential on SCI-CNP remains to be elucidated. Here, we demonstrated for the first time that intravenous DHA administrations with 3-day intervals (250 nmol/kg; starting 30 minutes after injury and maintained for 6 weeks) effectively prevented SCI-CNP development in a clinically relevant rat contusion model. SCI-CNP was assessed by a novel sensory profiling approach combining evoked pain measures and pain-related ethologically relevant rodent behaviours (burrowing, thigmotaxis, and place/escape avoidance) to mimic those for measuring human (sensory, affective, cognitive, and spontaneous) pain. Strikingly, already established SCI-CNP could be abolished partially by similar DHA administrations, starting from the beginning of week 4 after injury and maintained for 4 weeks. At spinal (epicenter and L5 dorsal horns) and supraspinal (anterior cingulate cortex) levels, both treatment regimens potently suppressed microglial and astrocyte activation, which underpins SCI-CNP pathogenesis. Spinal microgliosis, a known hallmark associated with neuropathic pain behaviours, was reduced by DHA treatments. Finally, we revealed novel potential roles of peroxisome proliferator–activated and retinoid X receptors and docosahexaenoyl ethanolamide (DHA's metabolite) in mediating DHA's effects on microglial activation. Our findings, coupled with the excellent long-term clinical safety of DHA even in surgical and critically ill patients, suggest that systemic DHA treatment is a translatable, effective, safe, and novel approach for preventing and managing SCI-CNP.

from PAIN - Featured Articles - Current Issue Highlights https://ift.tt/2NXf15Z
via IFTTT

A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy

Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, using a rodent model of experimental homocysteinemia, we report the causal association between homocysteine and the development of mechanical allodynia. Homocysteinemia-induced mechanical allodynia was reversed on pharmacological inhibition of T-type calcium channels. In addition, our in vitro studies indicate that homocysteine enhances recombinant T-type calcium currents by promoting the recycling of Cav3.2 channels back to the plasma membrane through a protein kinase C–dependent signaling pathway that requires the direct phosphorylation of Cav3.2 at specific loci. Altogether, these results reveal an unrecognized signaling pathway that modulates the expression of T-type calcium channels, and may potentially contribute to the development of peripheral neuropathy associated with homocysteinemia.

from PAIN - Featured Articles - Current Issue Highlights https://ift.tt/2O368bb
via IFTTT

Recurrent low back pain patients demonstrate facilitated pronociceptive mechanisms when in pain, and impaired antinociceptive mechanisms with and without pain

Low back pain (LBP) has been inconsistently associated with enhanced pronociceptive and impaired antinociceptive mechanisms. It remains unknown whether alterations are causal, consequential, or coincidental to pain presence. This study investigated pronociceptive and antinociceptive mechanisms in recurrent LBP (RLBP) patients across painful and pain-free periods, compared with age/sex-matched asymptomatic controls. During a painful episode (day 0) and when pain-free (day 28), 30 RLBP patients were assessed and compared with 30 controls over the same timeframe. Pressure pain thresholds were recorded bilaterally on the arm, back, and leg. Cuff algometry was used to assess cuff pressure pain detection threshold and cuff pain tolerance threshold on the lower legs, as well as temporal summation of pain (10 repeated painful cuff test stimuli on the dominant leg scored on a visual analogue scale) and conditioned pain modulation ([CPM]: cuff pain detection/tolerance threshold on dominant leg, before vs during painful cuff conditioning on the contralateral leg). Recurrent LBP patients displayed reduced pressure pain thresholds at the arm and back on day 0 compared with day 28 (P < 0.047) and with controls on day 0 (P < 0.049). Cuff pain detection threshold was reduced, and ratings of suprathreshold test stimuli were increased in RLBP patients on day 0 compared with day 28 (P < 0.02). Temporal summation of pain magnitude (increase in visual analogue scale scores) was enhanced in RLBP participants on day 0 compared with day 28 (P = 0.027) and with controls on day 0 (P = 0.039). Conditioned pain modulation magnitude (increased threshold during conditioning) was lower overall in RLBP participants than in controls (P = 0.021). Enhanced pronociceptive mechanisms were observed in RLBP patients. When pain-free, measures returned to similar levels as controls, except for CPM, which remained impaired.

from PAIN - Featured Articles - Current Issue Highlights https://ift.tt/2O0GWSD
via IFTTT

Effects of Fitness Level and Exercise Intensity on Pain and Mood Responses

Abstract

Background

The phenomenon of exercise‐induced hypoalgesia and concomitant mood changes is well established. How exercise‐induced hypoalgesia and affective responses are shaped by the intensity of an acute exercise bout and individual fitness levels is as yet not well understood. This study investigates whether heat pain threshold (PTh), pain tolerance (PTol), and affective parameters are modulated by the intensity of an acute exercise bout and/or individuals' fitness level. Stronger analgesic responses are hypothesized after high‐intensity exercise in physically fitter subjects, possibly in sync with concomitant mood changes.

Methods

Thirty‐three healthy men were recruited (sedentary: N=17 or recreational: N=14; mean age: 25.3±4.4 years). After a fitness assessment on a cycle ergometer, subjects underwent three experimental conditions on separate days: high (20 minutes exercise 20% above lactate threshold), low (20 minutes exercise 20% below lactate threshold) and control (seated rest). Before and after each intervention Positive and Negative Affect Schedule, PTh and PTol (cold water emersion test) were assessed.

Results

Results indicate an increase of the Positive Affect Scale (high: 26.7±9.0 vs. 32.9±7.1, p<0.001; low: 26.3±7.2 vs. 32.0±7.0, p<0.001) and PTh (high: 45.1±3.1 °C vs. 46.0±2.6 °C, p=0.003; low: 45.4±2.7 °C vs. 45.9±2.6 °C, p=0.012) after both exercise conditions. In an exploratory analysis, PTol significantly increased only after the high exercise condition (51.2±33.7 sec. vs. 72.4±64.0 sec., p=0.045). Fitness level was positively correlated with the increase in PTol from pre to post high‐intensity exercise (r=0.59, p(one‐tailed)=0.002).

Conclusion

Exercise‐induced hypoalgesia depends on exercise intensity and appears to be influenced by individual fitness status, independent of mood responses.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/37hsqxu
via IFTTT

[Correspondence] Time to revisit indications for cholecystectomy

Aafke van Dijk and colleagues1 presented the findings from their multicentre, randomised, non-inferiority trial (SECURE), designed to compare a conventional indication for cholecystectomy with a more restrictive and criteria-based strategy in patients with abdominal pain and ultrasound-proven gallstones. At 12-month follow-up, non-inferiority of restrictive strategy regarding pain improvement was not shown compared with standard of care.1

from The Lancet https://ift.tt/2NM41rS
via IFTTT

[Correspondence] Time to revisit indications for cholecystectomy – Author's reply

We thank Dimitrios Moris and Theodore Pappas for their comments and suggestions to further optimise the selection criteria for laparoscopic cholecystectomy in patients with abdominal pain and gallstones. We accept the concerns about the protocol violations. The SECURE trial1 was designed to better select patients for cholecystectomy, but it stops short of answering the question of how to treat patients with abdominal symptoms and gallstones.

from The Lancet https://ift.tt/33Qe3hg
via IFTTT

[Clinical Picture] Trigeminal neuralgia plus hemifacial spasm caused by a dilated artery: a case of painful tic convulsif syndrome

A 61-year-old woman came to our neurosurgery clinic complaining of spasms and episodic pain on the left side of her face; the spasms had been present for 20 years and the pain for 5 years. She said that initially the facial spasms affected only the corner of her left eye but over the years progressed to involve most of the muscles of the lower left side of her face. For the past 7 years, she had been given botulinum toxin injections twice per year, which had provided some relief. The pain, which developed alongside the spasms, was characterised by frequent episodes of excruciating, lancinating pain—rated by the patient as very severe using a visual analogue pain scale—along the ophthalmic and maxillary branches of the trigeminal nerve.

from The Lancet https://ift.tt/2poRoda
via IFTTT

The context of values in pain control: understanding the price effect in placebo analgesia

Placebo effects, a sum of different factors including non-specific effects, regression to the mean, natural history, and placebo responses, substantially contribute to clinical outcomes in diseases such as Parkinson's disease, depression, and immune function, as well as in acute and chronic pain conditions.10,33 Recent studies on placebo effects implicate the importance of informational context relative to medical treatments, most of which have no direct therapeutic effects on the body.42 One distinct feature of every therapeutic intervention is price, or treatment cost.

from The Journal of Pain https://ift.tt/2O8x8EN
via IFTTT

Sex differences in interleukin-6 responses over time following laboratory pain testing among patients with knee osteoarthritis

Knee osteoarthritis (KOA) is a chronic pain condition that is one of the leading causes of physical impairment and disability across the world.40 The prevalence of KOA is expected to continuously escalate due to population aging and increases in obesity rates.63 Women are particularly at-risk for developing chronic pain and KOA.20,43 Further, women generally report higher pain-related symptoms (including KOA symptoms57), evoked-pain sensitivity, and lower pain tolerance compared to men.20,43

from The Journal of Pain https://ift.tt/3724qOG
via IFTTT

Sensitivities to Thermal and Mechanical Stimuli: Adults with Sickle Cell Disease Compared to Healthy, Pain-free African American Controls

Until recent findings that sickle cell disease (SCD) pain has characteristics consistent with central or peripheral sensitization,12,27,28,43 it was typically viewed as acute or persistent pain and treated mostly with opioids. Often the etiology of SCD pain is thought to be only episodic, driven by vaso-occlusion and somatic or visceral tissue damage,1,2,4 however, it has become increasingly clear that adults with SCD also experience chronic pain. A growing body of evidence now supports,12,27,28,40,43, but is not conclusive, that sensitization contributes to chronic pain in some adults with SCD.

from The Journal of Pain https://ift.tt/2XepywM
via IFTTT

Nociception Coma Scale Revised allows to identify patients with preserved neural basis for pain experience.

The Nociception Coma Scale-Revised (NCS-R) was developed to help assess pain in patients with disorders of consciousness (DOC). Several studies have shown its sensitivity in assessing response to acute noxious stimuli. However, they failed to determine a reliable cut-off score that could be used to infer pain processing in these patients.This retrospective cross-sectional study aimed to determine a NCS-R cut-off score supporting preserved neural basis for pain experience, based on brain metabolism preservation as measured by fluorodeoxyglucose positron emission tomography (FDG-PET).

from The Journal of Pain https://ift.tt/2Xd4B53
via IFTTT

Ectopic pregnancy and miscarriage: diagnosis and initial management: summary of updated NICE guidance

What you need to knowThe guideline now includes new recommendations on the ultrasound features for diagnosis of a tubal ectopic pregnancyWomen without pain who have small ectopic pregnancies, low...

from Latest headlines from BMJ https://ift.tt/33I7kpz
via IFTTT

Efficacy and harms of orally, intramuscularly or intravenously administered glucocorticoids for sciatica: A systematic review and meta‐analysis

Abstract

Background

Sciatica can be a debilitating condition and there is limited guidance on the use of glucocorticoids administered via the oral, intramuscular or intravenous route for this condition. These represent viable treatment options in the primary care setting.

Objective

To evaluate the evidence on efficacy and harms of oral, IM and IV glucocorticoid administration for sciatica.

Databases and Data Treatment

MEDLINE, EMBASE, CENTRAL, CINAHL, PsycINFO (inception to October 2018) were searched for randomised placebo‐controlled trials evaluating oral, IV or IM glucocorticoid administration for sciatica. Two authors extracted outcomes data. Continuous pain and disability outcomes were converted to a 0 (no pain/disability) to 100 (worst pain/disability) scale. Data were pooled using a random effects model. Overall quality of evidence was assessed using GRADE. Primary outcomes were leg pain and disability. Primary follow‐up period was the immediate‐term (<2 weeks from administration). We also considered adverse events.

Results

Nine trials were eligible. One study [n=27] provided low quality evidence of a small reduction in disability with early administration of oral prednisone (within 1 week); MD ‐13.4 [‐23.3, ‐3.5] but not for pain MD ‐2.5 [‐16.9, 11.9]. There was low quality evidence from one study [n=78] of moderate reduction in disability and small reduction in pain with early (within 72‐hours of symptom onset) single intramuscular administration of methylprednisolone acetate; MD ‐24.5 [‐38.8, ‐10.2] and ‐14.0 [‐27.4, ‐0.6] respectively. There were no immediate‐term benefits with IV administration. There is moderate quality evidence from one study [n=267] that oral prednisone doubles the risk of adverse events compared with the placebo group; RR 95% CI 2.1 [1.4, 3.1].

Conclusion

The effects of glucocorticoids on immediate‐term leg pain or disability are uncertain. Future large high quality trials are needed to resolve this uncertainty.

from Wiley: European Journal of Pain: Table of Contents https://ift.tt/32LLG2J
via IFTTT

Most of the world’s population lacks access to opioid drugs for pain control

Smith and colleagues say that opioid prescribing is rising in many countries,1 with the result that use is “widespread.” While this may be true in high income countries, we must remember that lack of...

from Latest headlines from BMJ https://ift.tt/33HxoBf
via IFTTT