Difference of pain vulnerability in adult and juvenile rodents: the role of SIRT1-mediated ClC-3 trafficking in sensory neurons
Adults are more likely to suffer from chronic pain than minors, and its underlying mechanism remains unclear. SIRT1 an important age-related protein with function of lifespan extension; whether SIRT1 plays a role in the different pain vulnerability of adult and juvenile remains unclear. Here, we found that the expression level of SIRT1 in dorsal root ganglia (DRG) was related to the pain vulnerability. After nerve injury, the expression of SIRT1 in DRG was decreased in adult rodents whereas increased in juvenile rodents. Differential manipulation of SIRT1 abolished the different pain vulnerability between adult and juvenil...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Sphingomyelin is involved in multisite musculoskeletal pain: evidence from metabolomic analysis in 2 independent cohorts
This study sought to identify metabolic marker(s) for MSMP by metabolomic analysis. The Tasmanian Older Adult Cohort Study (TASOAC) provided the discovery cohort with the Newfoundland Osteoarthritis Study (NFOAS) providing the replication cohort. Multisite musculoskeletal pain was assessed by a self-reported pain questionnaire and defined as painful sites ≥4 in both the TASOAC and the NFOAS. Furthermore, MSMP was also defined as painful sites ≥7, whereas non-MSMP was defined as either painful sites (Source: Pain)
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

A peptide encoded within a 5′ untranslated region promotes pain sensitization in mice
Translational regulation permeates neuronal function. Nociceptors are sensory neurons responsible for the detection of harmful stimuli. Changes in their activity, termed plasticity, are intimately linked to the persistence of pain. Although inhibitors of protein synthesis robustly attenuate pain-associated behavior, the underlying targets that support plasticity are largely unknown. Here, we examine the contribution of protein synthesis in regions of RNA annotated as noncoding. Based on analyses of previously reported ribosome profiling data, we provide evidence for widespread translation in noncoding transcripts and regul...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Projections from the lateral parabrachial nucleus to the lateral and ventral lateral periaqueductal gray subregions mediate the itching sensation
In this study, lateral parabrachial nucleus (LPB), one of the most crucial relay stations in the ascending pathway, was taken as the input nucleus to examine the modulatory effect of l/vlPAG neurons that received LPB projections. Anatomical tracing, chemogenetic, optogenetic, and local pharmacological approaches were used to investigate the participation of the LPB-l/vlPAG pathway in itch and pain sensation in mice. First, morphological evidence for projections from vesicular glutamate transporter-2-containing neurons in the LPB to l/vlPAG involved in itch transmission has been provided. Furthermore, chemogenetic and optog...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Revisiting patient-related barriers to cancer pain management in the context of the US opioid crisis
Patient fear of addiction is a well-documented barrier to the use of analgesic medications for cancer pain control. Over the past 2 decades in the United States, an “opioid crisis” has arisen, accompanied by risk messages delivered through news outlets, public health education, and patient–provider communication. The purpose of this study was to determine if patient-related barriers to cancer pain management–specifically, fears of addiction–and related pain outcomes (pain severity, pain interference with daily life, and adequacy of pain management) have worsened over the last 20 years. A sampl...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Conditioned open-label placebo for opioid reduction after spine surgery: a randomized controlled trial
Placebo effects have traditionally involved concealment or deception. However, recent evidence suggests that placebo effects can also be elicited when prescribed transparently as “open-label placebos” (OLPs), and that the pairing of an unconditioned stimulus (eg, opioid analgesic) with a conditioned stimulus (eg, placebo pill) can lead to the conditioned stimulus alone reducing pain. In this randomized control trial, we investigated whether combining conditioning with an OLP (COLP) in the immediate postoperative period could reduce daily opioid use and postsurgical pain among patients recovering from spine surg...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Demise of nociceptive Schwann cells causes nerve retraction and pain hyperalgesia
Recent findings indicate that nociceptive nerves are not “free”, but similar to touch and pressure sensitive nerves, terminate in an end-organ in mice. This sensory structure consists of the nociceptive nerves and specialized nociceptive Schwann cells forming a mesh-like organ in subepidermis with pain transduction initiated at both these cellular constituents. The intimate relation of nociceptive nerves with nociceptive Schwann cells in mice raises the question whether defects in nociceptive Schwann cells can by itself contribute to pain hyperalgesia, nerve retraction, and peripheral neuropathy. We therefore e...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Empirically derived back pain subgroups differentiated walking performance, pain, and disability
Low back pain (LBP) is a leading cause of disability. However, the processes contributing to disability are not well understood. Therefore, this study (1) empirically derived LBP subgroups and (2) validated these subgroups using walking performance, pain, and disability measures. Seventy adults with LBP underwent testing for a priori determined sensory (temporal summation; conditioned pain modulation), psychological (positive affect/coping; negative coping), and motor (trunk extensor muscle activation during forward bending and walking) measures. A hierarchical cluster analysis determined subgroups that were then validated...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Ultrasound-guided transversus abdominis plane block vs trigger point injections for chronic abdominal wall pain: a randomized clinical trial
The primary aim of this randomized clinical trial is to investigate the effects of ultrasound-guided transversus abdominis plane (TAP) vs ultrasound-guided trigger point injections (TPIs) on numerical rating scale pain scores at month 3 follow-up in patients with a chronic abdominal wall pain. The primary outcome measure was the difference in mean numeric rating scale pain scores between the TAP and TPI groups at month 3 in an intent-to-treat (ITT) analysis. A total of 60 patients were randomized 1:1 to receive an ultrasound-guided TAP block (n = 30) or an ultrasound-guided TPI (n = 30). No significant group differences in...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Brainstem trigeminal fiber microstructural abnormalities are associated with treatment response across subtypes of trigeminal neuralgia
Neurosurgical treatments for trigeminal neuralgia (TN) can provide long-lasting pain relief; however, some patients fail to respond and undergo multiple, repeat procedures. Surgical outcomes can vary depending on the type of TN, but the reasons for this are not well understood. Neuroimaging studies of TN point to abnormalities in the brainstem trigeminal fibers; however, whether this is a common characteristic of treatment nonresponse across different subtypes of TN is unknown. Here, we used diffusion tensor imaging (DTI) to determine whether the brainstem trigeminal fiber microstructure is a common biomarker of surgical r...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Generalization of placebo pain relief
Efficacy of treatment is heavily dependent on experience and expectations. Moreover, humans can generalize from one experience to a perceptually similar but novel situation. We investigated whether and how this applies to pain relief, using ecologically valid tonic pain stimuli treated by surreptitiously lowering the applied temperature. Using different face cues, participants experienced better treatment from one physician than another. Participants were then tested on 6 additional face cues perceptually lying between both faces. Our data from 2 independent samples (N = 18 and N = 39) show a treatment experience effect, i...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Nonlinear increase of pain in distance-based and area-based spatial summation
When nociceptive stimulation affects a larger body area, pain increases. This effect is called spatial summation of pain (SSp). The aim of this study was to describe SSp as a function of the size or distance of a stimulated area(s) and to test how this function is shaped by the intensity and SSp test paradigm. Thirty-one healthy volunteers participated in a within-subject experiment. Participants were exposed to area-based and distanced-based SSp. For area-based SSp, electrocutaneous noxious stimuli were applied by up to 5 electrodes (5 areas) forming a line-like pattern; for distance-based SSp, the same position and lengt...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Two independent mouse lines carrying the Nav1.7 I228M gain-of-function variant display dorsal root ganglion neuron hyperexcitability but a minimal pain phenotype
Small-fiber neuropathy (SFN), characterized by distal unmyelinated or thinly myelinated fiber loss, produces a combination of sensory dysfunction and neuropathic pain. Gain-of-function variants in the sodium channel Nav1.7 that produce dorsal root ganglion (DRG) neuron hyperexcitability are present in 5% to 10% of patients with idiopathic painful SFN. We created 2 independent knock-in mouse lines carrying the Nav1.7 I228M gain-of-function variant, found in idiopathic SFN. Whole-cell patch-clamp and multielectrode array recordings show that Nav1.7 I228M knock-in DRG neurons are hyperexcitable compared with wild-type litterm...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Brief preoperative mind–body therapies for total joint arthroplasty patients: a randomized controlled trial
Abstract: Although knee and hip replacements are intended to relieve pain and improve function, up to 44% of knee replacement patients and 27% of hip replacement patients report persistent postoperative joint pain. Improving surgical pain management is essential. We conducted a single-site, 3-arm, parallel-group randomized clinical trial conducted at an orthopedic clinic, among patients undergoing total joint arthroplasty (TJA) of the hip or knee. Mindfulness meditation (MM), hypnotic suggestion (HS), and cognitive-behavioral pain psychoeducation (cognitive-behavioral pain psychoeducation) were each delivered in a sing...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Phenotyping peripheral neuropathic pain in male and female adolescents: pain descriptors, somatosensory profiles, conditioned pain modulation, and child–parent reported disability
Neuropathic pain (NeuP) can be difficult to diagnose and manage in children. Data regarding prevalence and sex-dependent differences are limited, and more detailed phenotyping is needed. This observational cohort study recruited adolescents (10-17 years) with NeuP or complex regional pain syndrome (CRPS). After pain history and NeuP questionnaires, quantitative sensory testing was performed. Individual z-score plots were calculated with body-region control measures and matched to mechanism-related sensory profiles (sensory loss, thermal hyperalgesia, and mechanical hyperalgesia). Conditioned pain modulation was assessed wi...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Chronic pain susceptibility is associated with anhedonic behavior and alterations in the accumbal ubiquitin-proteasome system
It remains unknown why on similar acute/subacute painful conditions, pain persists in some individuals while in others it resolves. Genetic factors, mood, and functional alterations, particularly involving the mesolimbic network, seem to be key. To explore potential susceptibility or resistance factors, we screened a large population of rats with a peripheral neuropathy and we isolated a small subset ( (Source: Pain)
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Long-term inflammatory pain does not impact exploratory behavior and stress coping strategies in mice
Pain puts patients at risk for developing psychiatric conditions such as anxiety and depression. Preclinical mouse models of pain-induced affective behavior vary widely in methodology and results, impairing progress towards improved therapeutics. To systematically investigate the effect of long-term inflammatory pain on exploratory behavior and stress coping strategy, we assessed male C57BL/6J mice in the forced swim test (FST), elevated zero maze, and open field test at 4 and 6 weeks postinjection of Complete Freund's Adjuvant, while controlling for testing order and combination. Inflammatory pain did not induce a passive...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Quantitative language features identify placebo responders in chronic back pain
Although placebo effect sizes in clinical trials of chronic pain treatments have been increasing, it remains unknown if characteristics of individuals' thoughts or previous experiences can reliably infer placebo pill responses. Research using language to investigate emotional and cognitive processes has recently gained momentum. Here, we quantified placebo responses in chronic back pain using more than 300 semantic and psycholinguistic features derived from patients' language. This speech content was collected in an exit interview as part of a clinical trial investigating placebo analgesia (62 patients, 42 treated; 20 not ...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Voluntary wheel running improves outcomes in an early life stress–induced model of urologic chronic pelvic pain syndrome in male mice
Patients with a history of early life stress (ELS) exposure have an increased risk of developing chronic pain and mood disorders later in life. The severity of ELS in patients with urologic chronic pelvic pain syndrome (UCPPS) is directly correlated with symptom severity and increased comorbidity, and is inversely related to likelihood of improvement. Voluntary exercise improves chronic pain symptoms, and our group and others have shown that voluntary wheel running can improve outcomes in stress-induced UCPPS models, suggesting that exercise may negate some of the outcomes associated with ELS. Here, we provide further evid...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Altered nociception in Alzheimer disease is associated with striatal-enriched protein tyrosine phosphatase signaling
Alzheimer disease (AD) is the most common form of dementia, accounting for approximately 60% of cases. In addition to memory loss, changes in pain sensitivity are found in a substantial proportion of patients with AD. However, the mechanism of nociception deficits in AD is still unclear. Here, we hypothesize that the nociception abnormality in AD is due to the aberrant activation of striatal-enriched protein tyrosine phosphatase (STEP) signaling, which modulates proteins related to nociception transduction. Our results indicated that the transgenic mice carrying human amyloid precursor protein (APP) gene had lower sensitiv...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Effect of anodal high-definition transcranial direct current stimulation on the pain sensitivity in a healthy population: a double-blind, sham-controlled study
High-definition transcranial direct current stimulation (HD-tDCS) of brain areas related to pain processing may provide analgesic effects evident in the sensory detection and pain thresholds. The somatosensory sensitivity was assessed after HD-tDCS targeting the primary motor cortex (M1) and/or the dorsolateral prefrontal cortex (DLPFC). Eighty-one (40 females) subjects were randomly assigned to 1 of 4 anodal HD-tDCS protocols (20 minutes) applied on 3 consecutive days: Sham-tDCS, DLPFC-tDCS, M1-tDCS, and DLPFC&M1-tDCS (simultaneous transcranial direct current stimulation [tDCS] of DLPFC and M1). Subjects and experimen...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Impact of pain and catastrophizing on the long-term course of depression in the general population: the HUNT pain study
In this study, a random cohort from the general population (n = 4764) answered questions about pain, catastrophizing, and depression at 5 assessments in yearly intervals. Linear mixed models showed that within persons, increases in pain intensity and catastrophizing were independently associated with increases in depressive symptoms {mean change = −1.12, 95% confidence interval (CI) [−1.32 to −0.91] and −1.29, 95% CI [−1.52 to −1.05], respectively}. In prospective analyses restricted to individuals without depression above cutoff at baseline, chronic pain increased the risk of endorsing ...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Enhancing analgesic spinal cord stimulation for chronic pain with personalized immersive virtual reality
Spinal cord stimulation (SCS) is an approved treatment for truncal and limb neuropathic pain. However, pain relief is often suboptimal and SCS efficacy may reduce over time, requiring sometimes the addition of other pain therapies, stimulator revision, or even explantation. We designed and tested a new procedure by combining SCS with immersive virtual reality (VR) to enable analgesia in patients with chronic leg pain. We coupled SCS and VR by linking SCS-induced paresthesia with personalized visual bodily feedback that was provided by VR and matched to the spatiotemporal patterns of SCS-induced paresthesia. In this cross-s...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Developing clinical prediction models for nonrecovery in older patients seeking care for back pain: the back complaints in the elders prospective cohort study
This study aimed to develop and internally validate 3 clinical prediction models for nonrecovery in this population. A prospective cohort study in general practice was conducted (Back Complaints in the Elders, Netherlands), including 675 patients>55 years with a new episode of care for back pain. Three definitions of nonrecovery were used combining 6-month and 12-month follow-up data: (1) persistent back pain, (2) persistent disability, and (3) perceived nonrecovery. Sample size calculation resulted in a maximum of 14 candidate predictors that were selected from back pain prognostic literature and clinical experience. M...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Fear-avoidance beliefs are associated with reduced lumbar spine flexion during object lifting in pain-free adults
There is a long-held belief that physical activities such as lifting with a flexed spine is generally harmful for the back and can cause low back pain (LBP), potentially reinforcing fear-avoidance beliefs underlying pain-related fear. In patients with chronic LBP, pain-related fear has been shown to be associated with reduced lumbar range of motion during lifting, suggesting a protective response to pain. However, despite short-term beneficial effects for tissue health, recent evidence suggests that maintaining a protective trunk movement strategy may also pose a risk for (persistent) LBP due to possible pronociceptive con...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Photobiomodulation therapy is not better than placebo in patients with chronic nonspecific low back pain: a randomised placebo-controlled trial
Photobiomodulation therapy (PBMT) has been used in several musculoskeletal disorders to reduce pain, inflammation, and promoting tissue regeneration. The current evidence about the effects of PBMT on low back pain (LBP) is still conflicting. We aimed to evaluate the effects of PBMT against placebo on pain intensity and disability in patients with chronic nonspecific LBP. This was a prospectively registered, randomised placebo-controlled trial, with blinded patients, therapists, and assessors. The study was conducted on an outpatient physical therapy clinic in Brazil, between April 2017 and May 2019. A total of 148 patients...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Upsurges in the joblessness and opioid epidemics in the United States after the COVID-19 epidemic: the plight of the jobless patient in the clinic
No abstract available (Source: Pain)
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Perspective Source Type: research

Prognostic factors for adolescent knee pain: an individual participant data meta-analysis of 1281 patients
Adolescent knee pain has a propensity for chronicity, impacting physical activity and health into adulthood. The aim of this study is to investigate prognostic factors in adolescents with knee pain using individual participant data (IPD) meta-analysis. Studies were identified through a systematic search and a collaborative group. We included IPD from prospective studies of adolescents (age 10-19 years) with nontraumatic knee pain (13 studies and 1516 adolescents with 1281 unique participants). Primary outcomes were pain intensity and function (Knee Injury and Osteoarthritis Outcome Score “Sport/Rec” subscale). ...
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Systematic Review and Meta-Analysis Source Type: research

Pivoting to virtual delivery for managing chronic pain with nonpharmacological treatments: implications for pragmatic research
No abstract available (Source: Pain)
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: Topical Review Source Type: research

Photobiomodulation therapy for chronic low back pain: time to move on
No abstract available (Source: Pain)
Source: Pain - May 27, 2021 Category: Anesthesiology Tags: PAIN Source Type: research

A novel human surrogate model of noninjurious sharp mechanical pain: Erratum
No abstract available (Source: Pain)
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Erratum Source Type: research

Intrathecal patient-controlled analgesia has nothing to do with breakthrough cancer pain
No abstract available (Source: Pain)
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Correspondence Source Type: research

Timeline of pain before dementia diagnosis: a 27-year follow-up study
In conclusion, these findings suggest that pain is a correlate or prodromal symptom rather than a cause of dementia. (Source: Pain)
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Therapeutic targeting of nitroglycerin-mediated trigeminovascular neuronal hypersensitivity predicts clinical outcomes of migraine abortives
Cranial hypersensitivity is a prominent symptom of migraine, exhibited as migraine headache exacerbated with physical activity, and cutaneous facial allodynia and hyperalgesia. The underlying mechanism is believed to be, in part, activation and sensitization of dural-responsive trigeminocervical neurons. Validated preclinical models that exhibit this phenotype have great utility for understanding putative mechanisms and as a tool to screen therapeutics. We have previously shown that nitroglycerin triggers cranial allodynia in association with migraine-like headache, and this translates to neuronal cranial hypersensitivity ...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

The effect of early procedural pain in preterm infants on the maturation of electroencephalogram and heart rate variability
This study describes the maturation of electroencephalogram (EEG) signals and heart rate variability in a prospective cohort of 92 preterm infants ( (Source: Pain)
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Reduction in movement-evoked pain and fatigue during initial 30-minute transcutaneous electrical nerve stimulation treatment predicts transcutaneous electrical nerve stimulation responders in women with fibromyalgia
We previously showed that 1 month of transcutaneous electrical nerve stimulation (TENS) reduces movement-evoked pain and fatigue in women with fibromyalgia (FM). Using data from this study (Fibromyalgia Activity Study with TENS [FAST]), we performed a responder analysis to identify predictors of clinical improvement in pain and fatigue with TENS, validated these models using receiver operator characteristic, and determined number needed to treat and number needed to harm. Participants were randomly assigned to active-TENS (2-125 Hz; highest-tolerable intensity), placebo-TENS, or no-TENS for 1 month. At the end of the rando...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Predicting pain: differential pain thresholds during self-induced, externally induced, and imagined self-induced pressure pain
During self-induced pain, a copy of the motor information from the body's own movement may help predict the painful sensation and cause downregulation of pain. This phenomenon, called sensory attenuation, enables the distinction between self-produced stimuli vs stimuli produced by others. Sensory attenuation has been shown to occur also during imagined self-produced movements, but this has not been investigated for painful sensations. In the current study, the pressure pain thresholds of 40 healthy participants aged 18 to 35 years were assessed when pain was induced by the experimenter (other), by themselves (self), or by ...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Phenotypic profile clustering pragmatically identifies diagnostically and mechanistically informative subgroups of chronic pain patients
Traditional classification and prognostic approaches for chronic pain conditions focus primarily on anatomically based clinical characteristics not based on underlying biopsychosocial factors contributing to perception of clinical pain and future pain trajectories. Using a supervised clustering approach in a cohort of temporomandibular disorder cases and controls from the Orofacial Pain: Prospective Evaluation and Risk Assessment study, we recently developed and validated a rapid algorithm (ROPA) to pragmatically classify chronic pain patients into 3 groups that differed in clinical pain report, biopsychosocial profiles, f...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Open-label placebo for chronic low back pain: a 5-year follow-up
Long-term follow-up of patients treated with open-label placebo (OLP) are nonexistent. In this article, we report a 5-year follow-up of a 3-week OLP randomized controlled trial (RCT) in patients with chronic low back pain. We recontacted the participants of original RCT and reassessed their pain, disability, and use of pain medication. We obtained follow-up data from 55 participants (82% of those who took OLP during the parent RCT), with a mean elapsed time between the end of the 3 weeks placebo trial and the follow-up interview of 55 months (SD = 7.85). We found significant reductions in both pain and disability between t...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Long-term trajectories of chronic musculoskeletal pain: a 21-year prospective cohort latent class analysis
In conclusion, chronic pain was common in the population including 6% reporting persistent CWP, although the majority persistently reported NCP. Most people had stable pain status, but some had ongoing change in pain status over time including people who improved from chronic pain. It was possible to identify clinically relevant factors, characterizing trajectories of chronic pain development, that can be useful for identifying individuals at risk and potential targets for intervention. (Source: Pain)
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Intranasal delivery of an antisense oligonucleotide to the RNA-binding protein HuR relieves nerve injury-induced neuropathic pain
Neuropathic pain remains an undertreated condition and there is a medical need to develop effective treatments. Accumulating evidence indicates that posttranscriptional regulation of gene expression is involved in neuropathic pain; however, RNA processing is not clearly investigated. Our study investigated the role of HuR, an RNA binding protein, in promoting neuropathic pain and trauma-induced microglia activation in the spared nerve injury mouse model. To this aim, an antisense oligonucleotide (ASO) knockdown of HuR gene expression was used. Antisense oligonucleotides poorly cross the blood–brain barrier and an int...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Increase in trigeminal ganglion neurons that respond to both calcitonin gene–related peptide and pituitary adenylate cyclase–activating polypeptide in mouse models of chronic migraine and posttraumatic headache
A large body of animal and human studies indicates that blocking peripheral calcitonin gene–related peptide (CGRP) and pituitary adenylate cyclase–activating polypeptide (PACAP) signaling pathways may prevent migraine episodes and reduce headache frequency. To investigate whether recurring migraine episodes alter the strength of CGRP and PACAP signaling in trigeminal ganglion (TG) neurons, we compared the number of TG neurons that respond to CGRP and to PACAP (CGRP-R and PACAP-R, respectively) under normal and chronic migraine-like conditions. In a mouse model of chronic migraine, repeated nitroglycerin (NTG) a...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

IL-5 mediates monocyte phenotype and pain outcomes in fibromyalgia
Fibromyalgia (FM) is characterized by widespread chronic pain, fatigue, and somatic symptoms. The influence of phenotypic changes in monocytes on symptoms associated with FM is not fully understood. The primary aim of this study was to take a comprehensive whole-body to molecular approach in characterizing relationships between monocyte phenotype and FM symptoms in relevant clinical populations. Lipopolysaccharide-evoked and spontaneous secretion of IL-5 and other select cytokines from circulating monocytes was higher in women with FM compared to women without pain. In addition, greater secretion of IL-5 was significantly ...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Hippocampus shape deformation: a potential diagnostic biomarker for chronic back pain in women
Sex differences in the quality and prevalence of chronic pain are manifold, with women generally presenting higher incidence and severity. Uncovering chronic pain–related sex differences inform neural mechanisms and may lead to novel treatment routes. In a multicenter morphological study (total n = 374), we investigated whether the shape of subcortical regions would reflect sex differences in back pain. Given the hormone-dependent functions of the hippocampus, and its role in the transition to chronic pain, this region constituted our primary candidate. We found that the anterior part of the left hippocampus (alHP) p...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Headache in girls and boys growing up from age 11 to 20 years: the Prevention and Incidence of Asthma and Mite Allergy birth cohort study
The striking difference between men and women in headache prevalence is suggested to develop in adolescence. Although headaches are common and affect quality of life and daily functioning, the evidence needed to develop effective counselling and preventive approaches is still limited. Using data collected at age 11, 14, 17, and 20 years in the Dutch Prevention and Incidence of Asthma and Mite Allergy birth cohort study (n = 3064 with ≥ 1 questionnaire), we assessed headache prevalence and incidence in girls and boys and explored associations with early life, environmental, lifestyle, health, and psychosocial factors. As...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

G protein–coupled receptor GPR151 is involved in trigeminal neuropathic pain through the induction of Gβγ/extracellular signal-regulated kinase-mediated neuroinflammation in the trigeminal ganglion
Trigeminal nerve injury–induced neuropathic pain is a debilitating chronic orofacial pain syndrome but lacks effective treatment. G protein–coupled receptors (GPCRs), especially orphan GPCRs (oGPCRs) are important therapeutic targets in pain medicine. Here, we screened upregulated oGPCRs in the trigeminal ganglion (TG) after partial infraorbital nerve transection (pIONT) and found that Gpr151 was the most significantly upregulated oGPCRs. Gpr151 mRNA was increased from pIONT day 3 and maintained for more than 21 days. Furthermore, GPR151 was expressed in the neurons of the TG after pIONT. Global mutation or kno...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Characterizing chronic pain phenotypes in multiple sclerosis: a nationwide survey study
Chronic pain is highly prevalent in multiple sclerosis (MS). Pain heterogeneity may contribute to poor treatment outcomes. The aim of this study was to characterize pain phenotypes distributions in persons with MS and compare pain phenotypes in terms of pain intensity, frequency of chronic overlapping pain conditions, and use and analgesic effects of different classes of pain medications. Data were collected through a national web-based survey with measures of neuropathic (painDETECT) and nociplastic pain (Fibromyalgia Survey Criteria), chronic overlapping pain conditions, and pain medication use and pain relief. In a samp...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Cage-lid hanging behavior as a translationally relevant measure of pain in mice
The development of new analgesic drugs has been hampered by the inability to translate preclinical findings to humans. This failure is due in part to the weak connection between commonly used pain outcome measures in rodents and the clinical symptoms of chronic pain. Most rodent studies rely on the use of experimenter-evoked measures of pain and assess behavior under ethologically unnatural conditions, which limits the translational potential of preclinical research. Here, we addressed this problem by conducting an unbiased, prospective study of behavioral changes in mice within a natural homecage environment using convent...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

C5a complement and cytokine signaling mediate the pronociceptive effects of complex regional pain syndrome patient IgM in fracture mice
It has been proposed that complex regional pain syndrome (CRPS) is a posttraumatic autoimmune disease. Previously, we observed that B cells contribute to CRPS-like changes in a mouse tibia fracture model, and that early (12 months duration) CRPS patient IgM (but not IgG) caused nociceptive sensitization in muMT fracture mice, but intraplantar injection of chronic CRPS IgM or IgG had no effect. We postulate that CRPS IgM antibodies bind to neoantigens in the fracture limb skin and corresponding spinal cord to activate C5a complement signaling in macrophages and microglia, evoking proinflammatory cytokine expression contribu...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research

Brain imaging signature of neuropathic pain phenotypes in small-fiber neuropathy: altered thalamic connectome and its associations with skin nerve degeneration
Small-fiber neuropathy (SFN) has been traditionally considered as a pure disorder of the peripheral nervous system, characterized by neuropathic pain and degeneration of small-diameter nerve fibers in the skin. Previous functional magnetic resonance imaging studies revealed abnormal activations of pain networks, but the structural basis underlying such maladaptive functional alterations remains elusive. We applied diffusion tensor imaging to explore the influences of SFN on brain microstructures. Forty-one patients with pathology-proven SFN with reduced skin innervation were recruited. White matter connectivity with the th...
Source: Pain - April 22, 2021 Category: Anesthesiology Tags: Research Paper Source Type: research