Opioids remain a central element of perioperative pain management despite increased utilization of multimodal adjuvant strategies intended to reduce their use. Contemporary use of methadone and buprenorphine, both conceived as opioid analgesics, is dominated by their essential roles in the treatment of opioid use disorder. Compared to usual care opioids, however, they provide improved post-operative pain control while reducing analgesic requirements. These findings argue for their expanded role within perioperative multimodal analgesia strategies.

Background:Chronic low back pain (cLBP) imposes a significant public health burden. Digital health interventions are increasingly used for chronic pain management, yet effective home-based therapies remain limited. We aimed to evaluate a novel, remotely delivered avatar-based video-guided acupuncture imagery treatment (AB-VGAIT) for cLBP. Methods:This parallel-group, randomised, controlled trial was performed at Massachusetts General Hospital (MA USA). Eligible participants, aged 18-75 years, had been experiencing cLBP for over six months and had at least 4/10 clinical pain on the low back pain numeric rating scale ranging from 0 to 10. Enrolled participants were randomly assigned (1:1) to either the AB-VGAIT or the avatar-based video-guided touch imagery treatment (AB-VGTIT; control) group. Participants underwent eight treatment sessions of either AB-VGAIT or AB-VGTIT over a 4-week period, wherein avatar-based, animated videos guided participants to imagine acupuncture (AB-VGAIT) or cotton stabs (AB-VGTIT) stimulation. Outcome evaluators and statisticians were blinded to group assignments, however participant blinding was not feasible due to the visual and interactive nature of the intervention. The primary outcome was the change from baseline in pain bothersomeness after 4 weeks of treatment. This study was registered with ClinicalTrials.gov, NCT03765879. Findings:Between June 22, 2021 and July 27, 2024, 60 participants were enrolled (n = 30 per group). Five (8.33%) participants did not complete the study, two (6.67%) in the AB-VGAIT group and three (10%) in the AB-VGTIT group. Although both groups demonstrated significant reductions in pain bothersomeness from baseline (AB-VGAIT: -1.71 [-2.38 to -1.04], p < 0.001; AB-VGTIT: -1.24 [-1.92 to -0.55], p = 0.001), no between-group difference was observed between AB-VGAIT and AB-VGTIT (-0.47 [-1.43 to 0.49], p = 0.586). Subgroup analyses stratified by sex, age, and baseline pain severity were consistent with the overall between-group findings. No serious adverse events occurred. Interpretation:Short duration, limited treatment frequency, and small sample size may restrict generalisability. No significant difference was observed between AB-VGAIT and AB-VGTIT; although both interventions yielded significant improvements in pain relief, suggesting each may offer a promising remote, self-administered digital intervention for cLBP. The scalable, non-invasive nature may help to bridge treatment gaps, particularly for individuals with limited access to in-person care. Future larger-scale trials are warranted to validate efficacy and generalisability. Funding:National Institutes of Health/National Center for Complementary and Integrative Health.

OBJECTIVE:To identify predictors of persistent opioid use in opioid-naïve individuals undergoing total joint arthroplasty. DESIGN:Retrospective cohort study. SETTING:Maine Health System. SUBJECTS:Opioid-naïve patients who underwent at least one total joint arthroplasty (knee, hip, or shoulder) between 2015 and 2020. METHODS:Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression was used to create a predictive model for persistent opioid use after surgery from a US Electronic Health Record dataset in the Observational Medical Outcomes Partnership Common Data Model format. 75% of the data was used to build the LASSO model using 10-fold cross-validation and 25% of the data was used to determine the optimal probability threshold for predicting the binary outcome. RESULTS:Out of 6432 patients, 12.3% (792) were identified as having persistent opioid use across combined total joint arthroplasties defined as at least one opioid prescription between 90 days and 1 year after surgery. Patients with persistent opioid use were more likely to be current smokers (OR 1.65), use antidepressants (OR 1.76), or have a diagnosis of post-traumatic stress disorder (OR 2.07) or a substance-related disorder (OR 1.69). Other factors associated with persistent opioid use included back pain (OR 1.43), dementia (OR 1.65), and body mass index over 40 (OR 2.50). The probability of persistent opioid use was not associated with age, sex, or ethnicity. CONCLUSIONS:This predictive model for persistent opioid use after total joint arthroplasty shows promise as an evidence-based, validated, and standardized tool for identifying high-risk patients before surgery in order to target strategies and interventions to reduce the reliance on opioids for postoperative pain control.

ABSTRACT:Our group has shown that translocator protein (TSPO) levels, a putative marker of neuroinflammation, are increased in the brain and spinal cord of patients with chronic low back pain (cLBP). Whether neuroinflammation might be a therapeutic target for this condition is unknown. In this phase II double-blind, placebo-controlled, randomized clinical trial, we sought to evaluate whether the tetracycline antibiotic minocycline, which is commonly used as a glial inhibitor in preclinical models, has an effect on brain TSPO levels in adults with cLBP. Participants randomly received 100-mg minocycline or placebo, once a day for 2 weeks. The primary outcome was the change (pretreatment vs posttreatment) in thalamic TSPO levels, measured using [11C]PBR28 positron emission tomography signal (standardized uptake value ratio) and analyzed with a mixed effect model. Secondary outcome measures included the change in Brief Pain Inventory, severity subscore. Among 60 enrolled participants, 48 completed the trial. Of these, 25 received minocycline (age [years], mean ± SD: 44.6 ± 16.9; 9 female), and 23 received placebo (49 ± 17.1; 9 female). The mean thalamic positron emission tomography standard uptake value ratio was very stable across visits in both groups, with no significant group-by-time interaction (P = 0.956). Similarly, both groups demonstrated a comparable decrease over time in Brief Pain Inventory severity scores (P = 0.018) and no significant group-by-time interaction (P = 0.329). Our results suggest that minocycline, at the tested regimen, may neither reduce brain TSPO levels nor have clinically meaningful effects on clinical pain in patients with cLBP.

We report a 30-case series from the Pain Management Center at the Massachusetts General Hospital where we have applied a guideline to convert chronic treatment for pain from full agonist opioids (FAO) to buprenorphine (BUP). Of the patients, 24 (80 percent) elected to continue BUP over FAO. Five conversions were stopped for side effects (fatigue) and/or lack of sufficient pain reduction. One patient elected not to participate on the day that the conversion was to begin. There were no major adverse events. We conclude that conversion to BUP should be considered as an alternative to treat patients on chronic opioids for pain.

The COVID-19 pandemic has exerted a global impact on both physical and mental health, and clinical populations have been disproportionally affected. To date, however, the mechanisms underlying the deleterious effects of the pandemic on pre-existing clinical conditions remain unclear. Here we investigated whether the onset of the pandemic was associated with an increase in brain/blood levels of inflammatory markers and MRIestimated brain age in patients with chronic low back pain (cLBP), irrespective of their infection history. A retrospective cohort study was conducted on 56 adult participants with cLBP (28 'Pre-Pandemic', 28 'Pandemic') using integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) and the radioligand [11C]PBR28, which binds to the neuroinflammatory marker 18 kDa Translocator Protein (TSPO). Image data were collected between November 2017 and January 2020 ('Pre-Pandemic' cLBP) or between August 2020 and May 2022 ('Pandemic' cLBP). Compared to the Pre-Pandemic group, the Pandemic patients demonstrated widespread and statistically significant elevations in brain TSPO levels (P =.05, cluster corrected). PET signal elevations in the Pandemic group were also observed when 1) excluding 3 Pandemic subjects with a known history of COVID infection, or 2) using secondary outcome measures (volume of distribution -VT- and VT ratio DVR) in a smaller subset of participants. Pandemic subjects also exhibited elevated serum levels of inflammatory markers (IL-16; P <.05) and estimated BA (P <.0001), which were positively correlated with [11C]PBR28 SUVR (r's >= 0.35; P's < 0.05). The pain interference scores, which were elevated in the Pandemic group (P <.05), were negatively correlated with [11C]PBR28 SUVR in the amygdala (r = -0.46; P<.05). This work suggests that the pandemic outbreak may have been accompanied by neuroinflammation and increased brain age in cLBP patients, as measured by multimodal imaging and serum testing. This study underscores the broad impact of the pandemic on human health, which extends beyond the morbidity solely mediated by the virus itself.

Background: Hypoxia is not uncommon in elderly patients during painless gastrointestinal endoscopy. This study aimed to determine the effectiveness of transcutaneous electrical acupoint stimulation (TEAS) in reducing the occurrence of hypoxia symptoms in elderly patients.Methods: Patients were randomly and equally grouped into sham control (n = 109) or TEAS group (n = 109) by using the random number table method. Patients in the TEAS group received electrical stimulation at the bilateral ST36 points 30 min before the examination until the end of the painless gastrointestinal endoscopy. Patients in the control group only had electrodes attached to bilateral nonacupoints in a similar pattern as the TEAS group without electrical stimulation. The primary endpoints measured were the incidence of hypoxia and severe hypoxia. The secondary endpoints included propofol dosage, sedation-related adverse events, hemodynamic parameters, surgical duration, patient recovery time, pain score, patient satisfaction, anesthesiologist satisfaction, and endoscopist satisfaction.Results: Of the 251 patients who participated in this study, 218 patients ended up completing the final study. The primary outcome was that, compared with group control, the incidence of hypoxia in group TEAS was reduced by 11% (19.3% vs. 8.3%, p = 0.018) and the incidence of severe hypoxia did not show a significant change (7.3% vs. 2.8%, p = 0.122). And there was a significant decrease in the occurrence of patients requiring emergency airway assistance (increased oxygen flow: 16.5% vs. 6.4%, p = 0.019, jaw thrust: 11.0% vs. 3.7%, p = 0.038, mask-assisted ventilation: 5.5% vs. 1.8%, p = 0.015).Conclusion: TEAS can reduce the incidence of hypoxia in elderly patients undergoing painless gastrointestinal endoscopy.Trial Registration: ClinicalTrials.gov identifier: .

OBJECTIVES:Buprenorphine maintenance for opioid use disorder (OUD) can present potential challenges for acute postoperative pain management. Provider practice and consistency of buprenorphine management strategies within institutions are unknown. This study aims to identify how providers nationwide manage patients on buprenorphine when they present for elective surgery.METHODS:A prospective survey of anesthesiologists was performed nationwide between November 2021 and March 2022. Survey respondents were selected from academic institutions identified using public databases and were also distributed to online social media platforms where members are required to verify medical licensure and hospital affiliation. Survey results were calculated and interpreted as the percentage rate of response.RESULTS:Survey invitations were sent to 190 institutions and returned 54 responses (28% response rate). An additional 12 completed surveys were obtained from online social media distribution resulting in 66 responses. Only 36% of respondents reported an established protocol for perioperative management of buprenorphine at their institution. Regarding consistency of buprenorphine management within institutions, the majority of respondents endorsed buprenorphine continuation without dose reduction in procedures where minimal pain was anticipated. However, there was a large discrepancy in buprenorphine management for surgeries with moderate-severe pain. Perioperative dosing frequency of buprenorphine was also inconsistent.CONCLUSIONS:The majority of institutions surveyed do not have an established protocol for perioperative buprenorphine management. In addition, there is provider variability in buprenorphine dosing for procedures with moderate-severe pain. This study highlights the need for dissemination of consensus guidelines for buprenorphine management.

Abstract Recently, we showed that patients with knee osteoarthritis (KOA) demonstrate alterations in the thalamic concentrations of several metabolites compared with healthy controls: higher myo-inositol (mIns), lower N-acetylaspartate (NAA), and lower choline (Cho). Here, we evaluated whether these metabolite alterations are specific to KOA or could also be observed in patients with a different musculoskeletal condition, such as chronic low back pain (cLBP). Thirty-six patients with cLBP and 20 healthy controls were scanned using 1H-magnetic resonance spectroscopy (MRS) and a PRESS (Point RESolved Spectroscopy) sequence with voxel placement in the left thalamus. Compared with healthy controls, patients with cLBP demonstrated lower absolute concentrations of NAA (P = 0.0005) and Cho (P < 0.05) and higher absolute concentrations of mIns (P = 0.01) when controlling for age, as predicted by our previous work in KOA. In contrast to our KOA study, mIns levels in this population did not significantly correlate with pain measures (eg, pain severity or duration). However, exploratory analyses revealed that NAA levels in patients were negatively correlated with the severity of sleep disturbance (P < 0.01), which was higher in patients compared with healthy controls (P < 0.001). Additionally, also in patients, both Cho and mIns levels were positively correlated with age (P < 0.01 and P < 0.05, respectively). Altogether, these results suggest that thalamic metabolite changes may be common across etiologically different musculoskeletal chronic pain conditions, including cLBP and KOA, and may relate to symptoms often comorbid with chronic pain, such as sleep disturbance. The functional and clinical significance of these brain changes remains to be fully understood.

For over two decades, the United States has grappled with our current opioid use disorder (OUD) epidemic [1]. In response, there has been a significant increase in the utilization of buprenorphine for OUD treatment, in part because of its distinctive pharmacologic properties [2, 3]. Compared to other opioids, buprenorphine has a long half-life, high binding affinity and slow dissociation from opioid receptors. Therefore, it resists displacement from these receptors when other opioids are used in conjunction [4]. The therapeutic doses of buprenorphine used for chronic pain treatment are significantly lower than those required for OUD treatment; therefore, opioid receptors are available when additional opioids are used concomitantly to enhance analgesia [5]. Conversely, when buprenorphine is used for OUD treatment, the diminished availability of opioid receptors resulting from the higher buprenorphine doses required can pose challenges for analgesic management [6]. Although routine practice involves continuing chronic pain buprenorphine formulations when acute pain is anticipated, the prevailing practice until recently has been withholding OUD dosed buprenorphine [4, 7]. Emerging evidence challenges these notions and supports opioid based analgesia can be achieved in parallel with OUD buprenorphine continuation [5, 8, 9]. In our previous retrospective study of surgical patients with OUD comparing patients where buprenorphine was continued or discontinued, we identified significantly higher outpatient opioid dispensing with buprenorphine discontinuation [5]. Similar findings were reported by Li et al., [8] where patients who continued buprenorphine perioperatively at various tapered doses received significantly fewer opioid prescriptions compared to those where buprenorphine was discontinued. Despite these studies, our recent national survey revealed significant variation in perioperative buprenorphine management practices [10]. Among surveyed anesthesiologists, only 36% of institutions had a protocol for buprenorphine management, and over a third endorsed either discontinuing buprenorphine in situations where moderate to severe pain was anticipated or adopting inconsistent management practices because of the lack of an institutional protocol. Premature discontinuation of buprenorphine is associated with an increased risk of opioid-induced relapse, making such practices concerning [11, 12]. The lack of clear guidance for buprenorphine management also extends to the critical care community. The 2018 Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility and Sleep Disruption in Adult Patients in the Intensive Care Unit did not provide recommendations for managing buprenorphine in patients maintained on this medication [13]. In our retrospective study evaluating the relationship between opioid exposure and buprenorphine administration in the intensive care unit, we identified the odds of receiving additional opioids were more than six times higher on days when buprenorphine was not administered compared to when it was given [14]. These findings support continuation of buprenorphine during critical illness, as it is associated with significantly decreased use of supplemental opioids, similar to current best practice established for perioperative populations. The above information reveals that high-level evidence on the analgesic outcomes based on buprenorphine management need to be conducted to establish a consensus for managing patients maintained on this medication [15]. In the face of the opioid crisis, evidence-based practices are crucial to guide clinicians and policymakers in providing the best possible care for patients maintained on buprenorphine. Aurora Quaye: Conceptualization (lead); investigation (equal); writing—original draft (lead); writing—review and editing (equal). Charlotte Crist: Conceptualization (supporting); investigation (supporting); writing—original draft (supporting); writing—review and editing (supporting). Simba Matoi: Conceptualization (supporting); investigation (supporting); writing—original draft (supporting); writing—review and editing (supporting). Yi Zhang: Conceptualization (equal); investigation (equal); writing—original draft (equal); writing—review and editing (equal). The authors would like to thank Janelle Richard for her assistance with formatting this manuscript for publication. None. Data sharing not applicable to this article as no datasets were generated or analysed for this Letter to the Editor.

Introduction: Both preclinical studies, and more recent clinical imaging studies, suggest that glia-mediated neuroinflammation may be implicated in chronic pain, and therefore might be a potential treatment target. However, it is currently unknown whether modulating neuroinflammation effectively alleviates pain in humans. This trial tests the hypothesis that minocycline, an FDA-approved tetracycline antibiotic and effective glial cell inhibitor in animals, reduces neuroinflammation and may reduce pain symptoms in humans with chronic low back pain.Methods and analysis: This study is a randomized, double-blind, placebo-controlled clinical trial. Subjects, aged 18-75, with a confirmed diagnosis of chronic (>= six months) low back pain (cLBP) and a self-reported pain rating of at least four out of ten (for at least half of the days during an average week) are enrolled via written, informed consent. Eligible subjects are randomized to receive a 14-day course of either active drug (minocycline) or placebo. Before and after treatment, subjects are scanned with integrated Positron Emission Tomography/ Magnetic Resonance Imaging (PET/MRI) using [11C]PBR28, a second-generation radiotracer for the 18 kDa translocator protein (TSPO), which is highly expressed in glial cells and thus a putative marker of neuro-inflammation. Pain levels are evaluated via daily surveys, collected seven days prior to the start of medication, and throughout the 14 days of treatment. General linear models will be used to assess pain levels and determine the treatment effect on brain (and spinal cord) TSPO signal.Trial registration number: ClinicalTrials.gov (NCT03106740).

Introduction Chronic pain is a debilitating medical problem that is difficult to treat. Neuroinflammatory pathways have emerged as a potential therapeutic target, as preclinical studies have demonstrated that glial cells and neuroglial interactions play a role in the establishment and maintenance of pain. Recently, we used positron emission tomography (PET) to demonstrate increased levels of 18 kDa translocator protein (TSPO) binding, a marker of glial activation, in patients with chronic low back pain (cLBP). Cannabidiol (CBD) is a glial inhibitor in animal models, but studies have not assessed whether CBD reduces neuroinflammation in humans. The principal aim of this trial is to evaluate whether CBD, compared with placebo, affects neuroinflammation, as measured by TSPO levels. Methods and analysis This is a double-blind, randomised, placebo-controlled, phase II clinical trial. Eighty adults (aged 18–75) with cLBP for >6 months will be randomised to either an FDA-approved CBD medication (Epidiolex) or matching placebo for 4 weeks using a dose-escalation design. All participants will undergo integrated PET/MRI at baseline and after 4 weeks of treatment to evaluate neuroinflammation using [ 11 C]PBR28, a second-generation radioligand for TSPO. Our primary hypothesis is that participants randomised to CBD will demonstrate larger reductions in thalamic [ 11 C]PBR28 signal compared with those receiving placebo. We will also assess the effect of CBD on (1) [ 11 C]PBR28 signal from limbic regions, which our prior work has linked to depressive symptoms and (2) striatal activation in response to a reward task. Additionally, we will evaluate self-report measures of cLBP intensity and bothersomeness, depression and quality of life at baseline and 4 weeks. Ethics and dissemination This protocol is approved by the Massachusetts General Brigham Human Research Committee (protocol number: 2021P002617) and FDA (IND number: 143861) and registered with ClinicalTrials.gov. Results will be published in peer-reviewed journals and presented at conferences. Trial registration number NCT05066308 ; ClinicalTrials.gov.

Study objective: VVZ-149 is a small molecule that inhibits the glycine transporter type 2 and the serotonin receptor 5-hydroxytryptamine 2A. In the present study, we investigated the efficacy and safety of VVZ-149 as a single-use injectable analgesic for treating moderate to severe postoperative pain after colorectal surgery. Design: Randomized, parallel group, double-blind Phase 2 clinical trial (NCT02489526). Setting: 3 academic institutions in the United States. Patients: 60 patients undergoing laparoscopic colorectal surgery. Interventions: A continuous 8-h intravenous infusion of VVZ-149 Injections (n = 40) or placebo (n = 20) administered after emergence from anesthesia. Measurements: The outcome measures included pain intensity (PI), opioid consumption via patient-controlled analgesia (PCA), and rescue dosing provided "as needed". Early rescue dosing with opioids postoperatively was associated with preoperative negative affect (anxiety, depression, and pain catastrophizing), enabling it to be used as an indirect measure of the affective component of pain. Efficacy outcomes were compared between treatment groups based on preoperative negative affect and early rescue dosing of opioids. Main results: Postoperative PI was non-significantly lower in patients receiving VVZ-149 compared to those receiving placebo. The VVZ-149 group had a 34.2% reduction in opioid consumption for 24 h post-dose, along with fewer PCA demands. Somnolence and headache was higher in the intervention group. For patients characterized by high levels of preoperative negative affect, the VVZ-149 group experienced a significant pain reduction and 40% less opioid use compared to the placebo group. Conclusions: VVZ-149 resulted in a non-significant reduction of postoperative pain during the first 8 h after surgery. Post hoc analysis indicates that VVZ-149 may benefit patients with negative affect who otherwise have higher postoperative opioid use.

Introduction Chronic pain is an extremely prevalent public health issue. However, the underlying mechanisms are poorly understood, thus limiting effective treatment options. Both preclinical studies, and more recent clinical imaging studies, suggest that glia-mediated neuroinflammation may be implicated in chronic pain, and therefore might be a potential treatment target. However, it is currently unknown whether modulating neuroinflammation effectively alleviates pain in humans. This trial tests the hypothesis that minocycline, an FDA-approved tetracycline antibiotic and effective glial cell inhibitor in animals, reduces neuroinflammation and may reduce pain symptoms in humans with chronic low back pain.Methods and analysis This study is a randomized, double-blind, placebo-controlled clinical trial. Subjects, aged 18-65, with a confirmed diagnosis of chronic (≥ six months) low back pain (cLBP) and a self-reported pain rating of at least four out of ten (for at least half of the days during an average week) are enrolled via written, informed consent. Eligible subjects are randomized to receive a 14-day course of either active drug (minocycline) or placebo. Before and after treatment, subjects are scanned with integrated Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) using [[11][1]C]PBR28, a second-generation radiotracer for the 18 kDa translocator protein (TSPO), which is highly expressed in glial cells and thus a putative marker of neuroinflammation. Pain levels are evaluated via daily surveys, collected seven days prior to the start of medication, and throughout the 14 days of treatment. General linear models are used to assess pain levels and determine the treatment effect on brain (and spinal cord) TSPO signal.Ethics and dissemination This study was approved by the Massachusetts General Hospital Institutional Review Board (Protocol Number: 2017P000179) and the U.S. Food and Drug Administration (IND Number: 142546). The results of the study will be disseminated via publications in peer-reviewed journals, presentations at conferences globally, and through various media.Trial registration number [ClinicalTrials.gov][2] ([NCT03106740][3])Strengths and limitations of this study ### Competing Interest StatementThe authors have declared no competing interest.### Clinical TrialIND142546, [NCT03106740][3]### Funding StatementThis work was supported by 1R01NS095937-01A1, awarded by the National Institute of Health (NIH). This grant supported all subject study-related drugs, devices, procedures, tests, and visits.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:Massachusetts General Brigham Institutional Review Board (Protocol: 2017P000179)I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data and materials used in the analyses may be provided by Marco L. Loggia and Massachusetts General Hospital, pending scientific review and a completed data use agreement/material transfer agreement beginning one year after publication of the results. Requests for all materials should be submitted to Marco L. Loggia at marco.loggia{at}mgh.harvard.edu. [1]: #ref-11 [2]: http://ClinicalTrials.gov [3]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03106740&atom=%2Fmedrxiv%2Fearly%2F2022%2F06%2F26%2F2022.06.22.22276757.atom

We recently showed elevated levels of the 18kDa translocator protein (TSPO), a marker of neuroinflammation, in chronic low back pain patients (cLBP) compared to healthy controls(Loggia et al., 2015). Here, we test whether TSPO signal 1) can further subtype cLBP patients based on their clinical presentation, and 2) is associated with functional connectivity measures (because neuroinflammation may affect neuronal communication(Clark et al., 2015)). Patients with axial (cLBPAX; n=26; 43.7±16.6 y.o.) or radicular cLBP (cLBPRAD; n=28; 48.3±13.2 y.o.) received an integrated PET/MRI scan with the TSPO ligand [11C]PBR28. TSPO signal was quantified using standardized uptake values normalized by whole-brain signal (SUVR). Functional connectivity from primary somatosensory cortex (S1) (i.e., a region significant in the PET group comparison) was calculated from BOLD resting-state fMRI data. Connectivity and PET measures were compared across groups, correlated with and against each other and against the Fibromyalgia Screening Questionnaire (FSQ) scores, measure of pain "centralization". Because two different scanners were used (BrainPET: 10 cLBPAX, 15 cLBPRAD; Biograph mMR: 16 cLBPAX, 13 cLBPRAD), scanner was included as a covariate in all analyses. Moreover, PET analyses also included Ala147Thr TSPO genotype, which predicts binding affinity to [11C]PBR28. In S1, TSPO signal and functional connectivity to the thalamus were: 1) higher in cLBPRAD compared to cLBPAX; 2) positively correlated with each other and 3) positively correlated with FSQ scores. Our data support the existence of different "neuroinflammatory signatures" in patients with different clinical presentation and that S1 neuroinflammatory signal is more pronounced in patients with higher pain "centralization". Further, because S1 TSPO signal was correlated to S1-thalamus connectivity, our data support an association between neuroinflammatory changes and changes in neuronal communication, possibly indicating that the observed alterations reflect "neurogenic neuroinflammation". Future studies are needed to determine whether neuroinflammation and related connectivity changes are possible therapeutic targets for chronic pain. 1R21NS087472-01A1; 1R01NS095937-01A; 1R01NS094306-01A1; W81XWH-14-1-0543.

We report a case in which sublingual buprenorphine was used to help transition a patient off intravenous (IV) opioid analgesics medications post-multiple abdominal procedures. Intravenous opioids are commonly used in inpatient surgical pain management for patients with severe pain who are unable to take oral medications. Typically, a short course of IV analgesics is used, followed by transition to oral analgesic regimen. However, in patients with poor gastrointestinal absorption, pain control can be challenging. We present this case to highlight how sublingual buprenorphine can be a useful agent for acute pain management, especially when conventional strategies provide suboptimal responses.