A bifunctional-biased mu-opioid agonist–neuropeptide FF receptor antagonist as analgesic with improved acute and chronic side effects
Opioid analgesics, such as morphine, oxycodone, and fentanyl, are the cornerstones for treating moderate to severe pain. However, on chronic administration, their efficiency is limited by prominent side effects such as analgesic tolerance and dependence liability. Neuropeptide FF (NPFF) and its receptors (NPFF1R and NPFF2R) are recognized as an important pronociceptive system involved in opioid-induced hyperalgesia and analgesic tolerance. In this article, we report the design of multitarget peptidomimetic compounds that show high-affinity binding to the mu-opioid receptor (MOPr) and NPFFRs. In vitro characterization of th...
Source: Pain - August 23, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Perioperative lidocaine infusions for the prevention of chronic postsurgical pain: a systematic review and meta-analysis of efficacy and safety
Chronic postsurgical pain (CPSP) occurs in 12% of surgical populations and is a high priority for perioperative research. Systemic lidocaine may modulate several of the pathophysiological processes linked to CPSP. This systematic review aims to identify and synthesize the evidence linking lidocaine infusions and CPSP. The authors conducted a systematic literature search of the major medical databases from inception until October 2017. Trials that randomized adults without baseline pain to perioperative lidocaine infusion or placebo were included if they reported on CPSP. The primary outcome was the presence of procedure-re...
Source: Pain - August 23, 2018 Category: Anesthesiology Tags: Systematic Review and Meta-Analysis Source Type: research

Pain as a threat to the social self: a motivational account
No abstract available (Source: Pain)
Source: Pain - August 23, 2018 Category: Anesthesiology Tags: Topical Review Source Type: research

Reproducible and replicable pain research: a critical review
No abstract available (Source: Pain)
Source: Pain - August 23, 2018 Category: Anesthesiology Tags: Topical Review Source Type: research

Perspective: update on pain education
No abstract available (Source: Pain)
Source: Pain - August 23, 2018 Category: Anesthesiology Tags: Perspectives Source Type: research

Chronic pain and opioid receptor availability: disentangling the molecular contributions and the “chicken or the egg” dilemma
No abstract available (Source: Pain)
Source: Pain - August 23, 2018 Category: Anesthesiology Tags: Commentary Source Type: research

Lidocaine infusions and preventative analgesia: can the answer to our prayers be hiding right under our noses?
No abstract available (Source: Pain)
Source: Pain - August 23, 2018 Category: Anesthesiology Tags: Commentary Source Type: research

Spinal GABAA receptors for pain control—lost in translation?
No abstract available (Source: Pain)
Source: Pain - August 23, 2018 Category: Anesthesiology Tags: Commentary Source Type: research

Interleukin-6 trans-signaling and pathological low back pain in patients with Paget disease of bone
The interleukin (IL)-6 biological system plays a key role in the pathogenesis of Paget disease (PD) of bone and pathological bone pain. Bone pain, particularly in the lower back region, is the most frequent symptom in patients with PD. This case–control study aimed to evaluate the relationship between the IL-6 system and low back pain (LBP) in patients with PD. We evaluated 85 patients with PD, with the disease localized in the lumbar spine, pelvis, and/or sacrum, and classified them based on the presence or absence of LBP, before and after aminobisphosphonate treatment. We also examined 32 healthy controls without L...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Chemokine (c-c motif) receptor 2 mediates mechanical and cold hypersensitivity in sickle cell disease mice
Approximately one-third of individuals with sickle cell disease (SCD) develop chronic pain. This debilitating pain is inadequately treated because the underlying mechanisms driving the pain are poorly understood. In addition to persistent pain, patients with SCD are also in a tonically proinflammatory state. Previous studies have revealed that there are elevated plasma levels of many inflammatory mediators including chemokine (c-c motif) ligand 2 (CCL2) in individuals with SCD. Using a transgenic mouse model of SCD, we investigated the contributions of CCL2 signaling to SCD-related pain. Inhibition of chemokine receptor 2 ...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Mice lacking Kcns1 in peripheral neurons show increased basal and neuropathic pain sensitivity
Voltage-gated potassium (Kv) channels are increasingly recognised as key regulators of nociceptive excitability. Kcns1 is one of the first potassium channels to be associated with neuronal hyperexcitability and mechanical sensitivity in the rat, as well as pain intensity and risk of developing chronic pain in humans. Here, we show that in mice, Kcns1 is predominantly expressed in the cell body and axons of myelinated sensory neurons positive for neurofilament-200, including Aδ-fiber nociceptors and low-threshold Aβ mechanoreceptors. In the spinal cord, Kcns1 was detected in laminae III to V of the dorsal horn wh...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Development of pain in older adults: a latent class analysis of biopsychosocial risk factors
In this study, latent class analysis was used to identify biopsychosocial risk classes in people aged 50 years and older, from The Irish Longitudinal Study on Ageing, who reported not often being troubled by pain at wave 1 and completed the 2-year follow-up at wave 2 (n = 4458). Four classes were identified based on 11 potential risk factors at wave 1. These classes were characterised as “Low Risk,” “Physical Health Risk,” “Mental Health Risk,” and “High Risk.” The Low-Risk class accounted for over half the sample (51.2%), whereas the High-Risk class represented 7.8% of the s...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Patients with chronic pain exhibit a complex relationship triad between pain, resilience, and within- and cross-network functional connectivity of the default mode network
Resilience is a psychological trait that strongly predicts chronic pain–related health outcomes. The neural correlates of both pain and trait resilience are critical to understand the brain–behaviour relationship in chronic pain; yet, neural correlates of resilience in chronic pain states are unknown. However, measures of pain perception and a wide range of psychological health measures have been linked to function of the default mode network (DMN). Thus, we aimed to determine the relationships between resilience, pain perception, and functional connectivity (FC) within the DMN and between the DMN and other bra...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Mu-opioid receptors in nociceptive afferents produce a sustained suppression of hyperalgesia in chronic pain
The latent sensitization model of chronic pain reveals that recovery from some types of long-term hyperalgesia is an altered state in which nociceptive sensitization persists but is suppressed by the ongoing activity of analgesic receptors such as μ-opioid receptors (MORs). To determine whether these MORs are the ones present in nociceptive afferents, we bred mice expressing Cre-recombinase under the Nav1.8 channel promoter (Nav1.8cre) with MOR-floxed mice (flMOR). These Nav1.8cre/flMOR mice had reduced MOR expression in primary afferents, as revealed by quantitative PCR, in situ hybridization, and immunofluorescence co...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Cortical astrocytes prime the induction of spine plasticity and mirror image pain
Peripheral nerve injury causes maladaptive plasticity in the central nervous system and induces chronic pain. In addition to the injured limb, abnormal pain sensation can appear in the limb contralateral to the injury, called mirror image pain. Because synaptic remodeling in the primary somatosensory cortex (S1) has critical roles in the induction of chronic pain, cortical reorganization in the S1 ipsilateral to the injured limb may also accompany mirror image pain. To elucidate this, we conducted in vivo 2-photon calcium imaging of neuron and astrocyte activity in the ipsilateral S1 after a peripheral nerve injury. We fou...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Downregulation of adenosine and adenosine A1 receptor contributes to neuropathic pain in resiniferatoxin neuropathy
This study examined this system at the level of ligand (through the ectonucleotidase activity of prostatic acid phosphatase [PAP]) and adenosine A1 receptors (A1Rs) in resiniferatoxin (RTX) neuropathy, a peripheral neurodegenerative disorder that specifically affects nociceptive nerves expressing transient receptor potential vanilloid type 1 (TRPV1). We conducted immunohistochemistry on dorsal root ganglion (DRG) neurons, high-performance liquid chromatography for functional assays, and pharmacological interventions to alter PAP and A1Rs in mice with RTX neuropathy. In DRG of RTX neuropathy, PAP(+) neurons were reduced com...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Dyadic analysis of siblings' relationship quality, behavioural responses, and pain experiences during experimental pain
This study examined whether sibling relationship quality was related to siblings' behaviours during experimental pain, and whether the behaviours of an observing sibling were related to children's pain outcomes. Ninety-two sibling dyads between 8 and 12 years old completed both observational and questionnaire measures of sibling relationship quality. Children took turns completing the cold-pressor task (CPT) in a counterbalanced order with their sibling present. Pain outcomes (intensity, fear, and tolerance) were recorded for each sibling, and the behaviour of the observing and participating siblings during the CPT were co...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Clinical indications associated with opioid initiation for pain management in Ontario, Canada: a population-based cohort study
Concerns over prescription opioids contributing to high levels of opioid use disorder and overdose have led policymakers and clinicians to seek means to reduce inappropriate and high-dose initial prescriptions. To inform such efforts, we sought to describe the clinical indications associated with opioid initiation and the characteristics of the initial prescriptions and patients through a retrospective population-based cohort study. Our cohort included Ontarians initiating prescription opioids for pain management between April 1, 2015, and March 31, 2016. We identified the apparent clinical indication for opioid initiation...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Neural pathways in medial septal cholinergic modulation of chronic pain: distinct contribution of the anterior cingulate cortex and ventral hippocampus
This study examined the contribution of MS cholinergic neurons and 2 neural pathways: MS–rostral anterior cingulate cortex (rACC) and MS–ventral hippocampal CA1 (vCA1), in modulating perceptual and affective pain behaviors in a mouse model of chronic inflammatory pain. We found that chronic pain activated MS cholinergic neurons and pyramidal neurons in the rACC, but suppressed pyramidal neuronal activities in the vCA1, all of which contributed to the maintenance of pathological pain. Chemogenetic inhibition of MS cholinergic neurons or the MS–rACC pathway inhibited rACC pyramidal neuronal activities and a...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Sources of opioid medication for misuse in older adults: results from a nationally representative survey
Despite increasing rates of prescription opioid (PO) misuse in adults 50 years of age and older, little research has investigated such misuse in this population. This work aimed to examine sources of misused opioid medication in adults 50 years and older, with comparisons to younger groups. Data were from the 2009 to 2014 National Survey on Drug Use and Health surveys. Prevalence rates of PO sources, misuse, and PO use disorder (POUD) symptoms were estimated. Design-based logistic regression investigated age-based differences in these factors and the association of sources with POUD symptoms and other concurrent substance ...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Modality-specific effects of aversive expectancy in the anterior insula and medial prefrontal cortex
We presented participants with visual cues predicting either a painful heat or disgusting odor, and assessed how they affected the subsequent subjective experience of stimuli from the same (within-modality) or opposite (cross-modal) modality. We found a reliable influence of expectancy on the subjective experience of stimuli whose modality matched that of the previous cue. At the brain level, this effect was mediated by the intermediate dysgranular section of the insula, whereas it was suppressed by more anterior agranular portions of the same region. Instead, no expectancy modulation was observed when the modality of the ...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Cognitive impairment in a rat model of neuropathic pain: role of hippocampal microtubule stability
We report here that rats exhibited memory deficits after spared nerve injury (SNI). We found that levels of stable microtubule (MT) were increased in the hippocampus of the rats with memory deficits. This increase in stable MT is marked by α-tubulin hyperacetylation. Paclitaxel, a pharmacological MT stabilizer, increased the level of stable MT in the hippocampus and induced learning and memory deficits in normal rats. Furthermore, paclitaxel reduced long-term potentiation in hippocampal slices and increased stable MT (evidenced by α-tubulin hyperacetylation) levels in hippocampal neuronal cells. Intracerebroven...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Comparison of the psychometric properties of 3 pain scales used in the pediatric emergency department: Visual Analogue Scale, Faces Pain Scale-Revised, and Colour Analogue Scale
Appropriate pain measurement relies on the use of valid, reliable tools. The aim of this study was to determine and compare the psychometric properties of 3 self-reported pain scales commonly used in the pediatric emergency department (ED). The inclusion criteria were children aged 6 to 17 years presenting to the ED with a musculoskeletal injury and self-reported pain scores ≥30 mm on the mechanical Visual Analogue Scale (VAS). Self-reported pain intensity was assessed using the mechanical VAS, Faces Pain Scale-Revised (FPS-R), and Colour Analogue Scale (CAS). Convergent validity was assessed by Pearson correlations and...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Altered prefrontal correlates of monetary anticipation and outcome in chronic pain
Chronic pain may alter both affect- and value-related behaviors, which represents a potentially treatable aspect of chronic pain experience. Current understanding of how chronic pain influences the function of brain reward systems, however, is limited. Using a monetary incentive delay task and functional magnetic resonance imaging (fMRI), we measured neural correlates of reward anticipation and outcomes in female participants with the chronic pain condition of fibromyalgia (N = 17) and age-matched, pain-free, female controls (N = 15). We hypothesized that patients would demonstrate lower positive arousal, as well as altere...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Wind-up in lamina I spinoparabrachial neurons: a role for reverberatory circuits
Wind-up is a frequency-dependent increase in the response of spinal cord neurons, which is believed to underlie temporal summation of nociceptive input. However, whether spinoparabrachial neurons, which likely contribute to the affective component of pain, undergo wind-up was unknown. Here, we addressed this question and investigated the underlying neural circuit. We show that one-fifth of lamina I spinoparabrachial neurons undergo wind-up, and provide evidence that wind-up in these cells is mediated in part by a network of spinal excitatory interneurons that show reverberating activity. These findings provide insight into...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Associations between onset of effort-reward imbalance at work and onset of musculoskeletal pain: analyzing observational longitudinal data as pseudo-trials
Existing evidence of an association between effort-reward imbalance (ERI) at work and musculoskeletal pain is limited, preventing reliable conclusions about the magnitude and direction of the relation. In a large longitudinal study, we examined whether the onset of ERI is associated with subsequent onset of musculoskeletal pain among those free of pain at baseline, and vice versa, whether onset of pain leads to onset of ERI. Data were from the Swedish Longitudinal Occupational Survey of Health (SLOSH) study. We used responses from 3 consecutive study phases to examine whether exposure onset between the first and second pha...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Efficacy of the Nav1.7 blocker PF-05089771 in a randomised, placebo-controlled, double-blind clinical study in subjects with painful diabetic peripheral neuropathy
The effect of PF-05089771, a selective, peripherally restricted Nav1.7 sodium channel blocker on pain due to diabetic peripheral neuropathy was investigated in a randomised, placebo and active-controlled parallel group clinical trial (NCT02215252). A 1-week placebo-run in the period was followed by a 4-week treatment period and a 1-week placebo run-out/taper-down period. Single-blind placebo was administered throughout run-in and run-out periods. Subjects were randomised to receive either PF-05089771 150 mg twice daily, pregabalin 150 mg twice daily, or placebo during the 4-week treatment period. One hundred thirty-five su...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Early workplace dialogue in physiotherapy practice improved work ability at 1-year follow-up—WorkUp, a randomised controlled trial in primary care
Workplace involvement in rehabilitation for patients with musculoskeletal pain may improve work ability. Convergence Dialogue Meeting (CDM) is a model aimed at helping the patient, the care giver, and the employer to support work ability and return-to-work. Our aim was to study the effect on work ability when adding a workplace dialogue according to CDM in physiotherapy practice for patients with pain in ordinary primary care. We conducted a prospective pairwise cluster randomised controlled trial (ClinicalTrials.gov ID: NCT02609750) in primary care involving 20 primary care rehabilitation units with 1-year follow-up. Adul...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Endogenous pain modulation in chronic orofacial pain: a systematic review and meta-analysis
This study aimed to provide, through a qualitative and quantitative synthesis of the available literature, overall estimates for TSP/CPM responses in patients with OFP relative to controls. MEDLINE, Embase, and the Cochrane databases were searched, and references were screened independently by 2 raters. Twenty-six studies were included for qualitative review, and 22 studies were included for meta-analysis. Traditional meta-analysis and robust variance estimation were used to synthesize overall estimates for standardized mean difference. The overall standardized estimate for TSP was 0.30 (95% confidence interval: 0.11-0.49;...
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Systematic Review and Meta-Analysis Source Type: research

A crucial administration timing separates between beneficial and counterproductive effects of opioids on postoperative pain
No abstract available (Source: Pain)
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Topical Review Source Type: research

Human T-lymphotrophic virus—a neglected cause of chronic pain?
No abstract available (Source: Pain)
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Topical Review Source Type: research

Importance of being collaborative for return to work with back pain
No abstract available (Source: Pain)
Source: Pain - July 26, 2018 Category: Anesthesiology Tags: Commentary Source Type: research

Chronic pain and fatigue: timescale, feedback, and overrides
No abstract available (Source: Pain)
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Correspondence Source Type: research

Reply
No abstract available (Source: Pain)
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Correspondence Source Type: research

Sense and sensibility—logical approaches to profiling in animal models
No abstract available (Source: Pain)
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Correspondence Source Type: research

Functional imaging in microfluidic chambers reveals sensory neuron sensitivity is differentially regulated between neuronal regions
Primary afferent sensory neurons are incredibly long cells, often traversing distances of over 1 m in humans. Cutaneous sensory stimuli are transduced in the periphery by specialised end organs or free nerve endings, which code the stimulus into electrical action potentials that propagate towards the central nervous system. Despite significant advances in our knowledge of sensory neuron physiology and ion channel expression, many commonly used techniques fail to accurately model the primary afferent neuron in its entirety. In vitro experiments often focus on the cell somata and neglect the fundamental processes of peripher...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Chronic pain impairs cognitive flexibility and engages novel learning strategies in rats
Cognitive flexibility, the ability to adapt behavior to changing outcomes, is critical to survival. The prefrontal cortex is a key site of cognitive control, and chronic pain is known to lead to significant morphological changes to this brain region. Nevertheless, the effects of chronic pain on cognitive flexibility and learning remain uncertain. We used an instrumental paradigm to assess adaptive learning in an experimental model of chronic pain induced by tight ligation of the spinal nerves L5/6 (spinal nerve ligation model). Naive, sham-operated, and spinal nerve ligation (SNL) rats were trained to perform fixed-ratio, ...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Hyperpolarization-activated cyclic nucleotide–gated channels contribute to spontaneous activity in L4 C-fiber nociceptors, but not Aβ-non-nociceptors, after axotomy of L5-spinal nerve in the rat in vivo
Peripheral neuropathic pain associated with partial nerve injury is believed to be driven partly by aberrant spontaneous activity (SA) in both injured and uninjured dorsal root ganglion (DRG) neurons. The underlying ionic mechanisms are not fully understood, but hyperpolarization-activated cyclic nucleotide–gated (HCN) channels which underlie the excitatory Ih current have been implicated in SA generation in axotomized A-fiber neurons after L5-spinal nerve ligation/axotomy (SNL/SNA). Here, using a modified model of SNA (mSNA) which involves, in addition to L5-SNA, loose ligation of the L4-spinal nerve with neuroinfla...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Bivalent ligand MCC22 potently attenuates nociception in a murine model of sickle cell disease
In this study, we used the Townes transgenic mouse model of SCD to investigate the antinociceptive efficacy of the bivalent ligand, MCC22, and compared its effectiveness with morphine. MCC22 consists of a mu-opioid receptor agonist and a chemokine receptor-5 (CCR5) antagonist that are linked through a 22-atom spacer. Our results show that intraperitoneal administration of MCC22 produced exceptionally potent dose-dependent antihyperalgesia as compared to morphine, dramatically decreased evoked responses of nociceptive dorsal horn neurons, and decreased expression of proinflammatory cytokines in the spinal cord. Moreover, to...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Machine-learned analysis of the association of next-generation sequencing–based human TRPV1 and TRPA1 genotypes with the sensitivity to heat stimuli and topically applied capsaicin
Heat pain and its modulation by capsaicin varies among subjects in experimental and clinical settings. A plausible cause is a genetic component, of which TRPV1 ion channels, by their response to both heat and capsaicin, are primary candidates. However, TRPA1 channels can heterodimerize with TRPV1 channels and carry genetic variants reported to modulate heat pain sensitivity. To address the role of these candidate genes in capsaicin-induced hypersensitization to heat, pain thresholds acquired before and after topical application of capsaicin and TRPA1/TRPV1 exomic sequences derived by next-generation sequencing were assesse...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Gray matter correlates of pressure pain thresholds and self-rated pain sensitivity: a voxel-based morphometry study
Individual differences in sensitivity to pain are large and have clinical and scientific importance. Although heavily influenced by situational factors, they also relate to genetic factors and psychological traits, and are reflected by differences in functional activation in pain-related brain regions. Here, we used voxel-based morphometry to investigate if individual pain sensitivity is related to local gray matter volumes. Pain sensitivity was determined using (1) index finger pressure pain thresholds (PPTs) and (2) pain intensity ratings of imagined painful situations as assessed by the Pain Sensitivity Questionnaire (P...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Temporal dynamics of pain: an application of regime-switching models to ecological momentary assessments in patients with rheumatic diseases
This study examined whether regime-switching models, which capture processes characterized by recurrent shifts between different states, provide clinically relevant information for characterizing individuals based on their temporal pain patterns. Patients with rheumatic diseases (N = 116) provided 7 to 8 momentary pain ratings per day for 2 weekly periods, separated by 3 months. Regime-switching models extracted measures of Average pain (mean level over time), Amplitude (magnitude of shifts in pain levels), Persistence (average duration of pain states), and Dominance (relative duration of higher vs lower pain states) for e...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Comparative transcriptome profiling of the human and mouse dorsal root ganglia: an RNA-seq–based resource for pain and sensory neuroscience research
We present our work as an online, searchable repository (https://www.utdallas.edu/bbs/painneurosciencelab/sensoryomics/drgtxome), creating a valuable resource for the community. Our analyses provide insight into DRG biology for guiding development of novel therapeutics and a blueprint for cross-species transcriptomic analyses. (Source: Pain)
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

How central is central poststroke pain? The role of afferent input in poststroke neuropathic pain: a prospective, open-label pilot study
Central poststroke pain (CPSP) is a neuropathic pain disorder, the underlying mechanisms of which are not well understood. It has been suggested that stroke-associated loss of inhibitory neurons in the spinothalamic tract causes disinhibition of thalamic neurons, which autonomously generate ectopic nociceptive action potentials responsible for the pain experience. We hypothesized that CPSP is a result of misinterpretation of afferent sensory input by the sensitized neurons within the brain, rather than generated spontaneously by the damaged central nervous system (CNS) neurons. To test this hypothesis, we prospectively rec...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Chemokine CCL2 and its receptor CCR2 in the dorsal root ganglion contribute to oxaliplatin-induced mechanical hypersensitivity
Activation of innate immune mechanisms within the dorsal root ganglion and spinal dorsal horn has been shown to play a key role in the development of neuropathic pain including paclitaxel-related chemotherapy-induced peripheral neuropathy (CIPN). Here, we tested whether similar mechanisms are generalizable to oxaliplatin-induced CIPN. After a single intraperitoneal injection of 3 mg/kg oxaliplatin, mechanical withdrawal threshold and the expression of C-C chemokine ligand 2 (CCL2) and its receptor, CCR2, in the dorsal root ganglion were measured by behavioral testing and immunohistochemical staining, respectively. Mechanic...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Spinal manipulation and exercise for low back pain in adolescents: a randomized trial
Low back pain (LBP) is common in adolescence, but there is a paucity of high-quality research to inform care. We conducted a multicenter randomized trial comparing 12 weeks of spinal manipulative therapy (SMT) combined with exercise therapy (ET) to ET alone. Participants were 185 adolescents aged 12 to 18 years with chronic LBP. The primary outcome was LBP severity at 12, 26, and 52 weeks. Secondary outcomes included disability, quality of life, medication use, patient- and caregiver-rated improvement, and satisfaction. Outcomes were analyzed using longitudinal linear mixed effect models. An omnibus test assessing differen...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Quantitative sensory testing after macroreplantation: evidence for a specific somatosensory profile
A comprehensive functional recovery is one of the criteria for successful replantation of an amputated limb. Functionality of a replanted limb is strongly dependent on its regained sensibility. In previous studies concerning the sensibility of replanted limbs, only a few somatosensory submodalities were examined in small samples. The purpose of this study is to provide a full pattern of somatosensory symptoms after replantation. Quantitative sensory testing was performed according to a standardized protocol in a sample of 15 patients who underwent replantation of their upper limb proximal to the radiocarpal joint (macrorep...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Sustained and repeated mouth opening leads to development of painful temporomandibular disorders involving macrophage/microglia activation in mice
This study suggests that mouth opening for an extended period during dental treatments or oral intubations may risk the development of chronic TMD and inflammation associated with macrophage and microglia in the tissue and trigeminal system contributes to the development of TMD pain. (Source: Pain)
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Reduced selective learning in patients with fibromyalgia vs healthy controls
This study is the first in directly assessing differences in selective learning between patients with FM and HCs using a blocking procedure. (Source: Pain)
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research

Protease-activated receptor 1 is implicated in irritable bowel syndrome mediators–induced signaling to thoracic human sensory neurons
Proteases and protease-activated receptors (PARs) are major mediators involved in irritable bowel syndrome (IBS). Our objectives were to decipher the expression and functionality (calcium signaling) of PARs in human dorsal root ganglia (DRG) neurons and to define mechanisms involved in human sensory neuron signaling by IBS patient mediators. Human thoracic DRG were obtained from the national disease resource interchange. Expression of PAR1, PAR2, and PAR4 was assessed by immunohistochemistry and quantitative reverse transcription PCR (RT-qPCR) in whole DRG or in primary cultures of isolated neurons. Calcium signaling in re...
Source: Pain - June 26, 2018 Category: Anesthesiology Tags: Research Paper Source Type: research