Pain Pathways Research Articles

Integrated hip surveillance pathways for pain, function and quality of life in children with Cerebral Palsy: A systematic literature review.

To determine the effectiveness of integrated hip surveillance pathways on pain, function and quality of life (QOL) in children with Cerebral Palsy (CP). A systematic literature review, designed, conducted and reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. confirmed CP diagnosis, management under recognised international hip surveillance pathways, outcome measures of hip displacement plus at least one other relevant to pain, function or QOL. 100 articles were identified. 12 full text articles were screened, and four were included. Reduced range of movement was associated with hip pain in children with CP. Increasing age, Gross Motor Function Classification Score (GMFCS) and migration percentage (MP) were associated with increased hip pain. General health declined with increased age. Increased MP and GMFCS level were associated with interruption to activities of daily living. Outcomes relating to function and QOL are under-researched in the current integrated hip surveillance pathway evidence-base. Wider outcomes related to function and QOL need to be included to capture the wider impact on children who are at risk of hip dislocation. Increased pain was associated with reduced joint range and increased migration percentage. Pain also increased with greater age and Gross Motor Function Classification Score. Early orthopaedic intervention for hip displacement may not successfully mitigate pain. Effectiveness of integrated pathways on function and quality of life is under-evidenced. Studies investigating integrated pathways and holistic outcomes are needed to inform practice.

Sleep Efficiency Mediates the Association Between Neighborhood Disadvantage and Knee Osteoarthritis Pain: Findings from the Understanding Pain and Limitations in Osteoarthritic Disease Study 2.

The objective was to examine potential pathways linking neighborhood disadvantage to pain severity in individuals with knee pain consistent with or at risk for Knee Osteoarthritis (KOA). The current investigation is a cross-sectional analysis. Data were collected from 140 mid-to older non-Hispanic White and non-Hispanic Black adults from the Understanding Pain and Limitations in Osteoarthritic Disease Study 2 (UPLOAD 2). Relationships among neighborhood disadvantage, sleep efficiency, pain catastrophizing, and pain severity were assessed. Neighborhood disadvantage was quantified using the Area Deprivation Index (ADI) and actigraphy data were used to assess sleep efficiency. The Coping Strategies Questionnaire-Revised catastrophizing subscale and WOMAC (Western Ontario and McMaster Universities Arthritis Index) pain severity scale were used to assess pain catastrophizing, and pain severity, respectively. A serial mediation model assessed the neighborhood➔sleep➔catastrophizing➔pain pathway, as well as neighborhood➔sleep➔pain, and neighborhood➔catastrophizing➔pain pathways. Greater neighborhood disadvantage was associated with worse sleep efficiency, ultimately contributing to greater pain severity. While neither neighborhood disadvantage nor sleep efficiency were associated with pain catastrophizing, pain catastrophizing itself was associated with greater KOA pain. Neighborhood disadvantage impacts KOA pain outcomes through sleep efficiency, but not pain catastrophizing, thereby highlighting environmental aspects that impact sleep as potential targets for intervention.

The use of a point of care high sensitivity troponin in the investigation of patients presenting to the Emergency Department with undifferentiated chest pain

Abstract Background In 2012 in a hospital, New Zealand, a chest pain pathway was instituted for the use in patients presenting to the Emergency Department (ED) with undifferentiated chest pain. This reduced hospital admissions and ED length of stay (LOS) without adversely affecting outcomes. The pathway consists of risk stratification combined with ECG and troponin testing. The pathway suggests, but does not enforce, that low risk patients can be discharged after a single troponin, intermediate risk patients are for serial troponins (which can be done in ED or the next day in the community), with further testing if appropriate, and high risk patients are reviewed by Cardiology or General medicine. In August 2023, Siemens point of care high sensitivity troponin I (POC-hsTnI) was introduced for the use in ED, although Beckman laboratory troponin I (Lab–hsTnI) is still available. A POC test reduces result turnaround times but until recently there has been a lack of POC assays fulfilling criteria for "high sensitivity". Purpose To ascertain whether the availability of a POC-hsTnI in the ED is a viable option for use in the chest pain pathway Methods A 1 month "snap shot" of all consecutive patients presenting to the ED with chest pain was undertaken and the patients followed for adverse events using electronic notes review. October 2023 was selected for the post POC-hsTnI period and compared with April 2022. Results There were 688 patients presenting to ED with undifferentiated chest pain during October 2023 with a type 1 acute myocardial infarction (AMI) rate of 80 (11.6%), median age 58 (41-72), female 335 (48.7%). POC-hsTnI was used in isolation in 377 (54.8%), in conjunction with Lab-hsTnI in 218 (31.7%) and Lab-hsTnI was used alone in 93 (13.5%). The median turnaround time for POC-hsTnI was 11 minutes (10-11) compared with Lab-hsTnI 87 minutes (61-129). The POC-hsTnI was less sensitive for AMI than the Lab-hsTnI on presentation using the upper reference limit, 72.1% (60.6-81.6) versus 91.5% (83.0-96.4). However, when used with risk stratification, there were no excess adverse events (cardiac death or AMI) at 4 months in patients discharged with a diagnosis of non-cardiac chest pain – 7 (1.4%) (n=495) versus 5 (1.2%), (n=424) in 2022. Median LOS in the ED was 4.4 hours (2.9-6.2) versus 4.0h (3.0-5.9) in 2022. However, a higher proportion of patients had a second cTn: 414 (60.2%) versus 309 (48.4%) and a lower proportion had their second troponin the next day in the community, 28 (6.7%) versus 56 (18.1%). Conclusion The use of a POC-hsTnI is a practical solution to reduce turnaround times for troponin results and has the potential to reduce LOS or allow serial troponins to be measured in a timely manner during their ED visit, obviating the need for a next day community troponin. Whilst POC-hsTnI has a lower early sensitivity for AMI, the use of POC-hsTnI as part of a pathway does not adversely affect outcomes.

Analysis of Chemical Composition, Antioxidant Capacity, Acute Toxicity, and Antinociceptive Properties of Aqueous Extract of Origanum majorana L.

Phytotherapy, the use of plant-derived compounds for medicinal purposes, is increasingly recognized as a vital component of modern therapeutics. This study investigates the aqueous extract of Origanum majorana L. (AEOM), evaluating its phytochemical composition, safety, antioxidant activity, and pharmacological effects. Analysis via LC-MS/MS identified a variety of phenolic compounds, with gallic acid, caffeic acid, and chlorogenic acid standing out for their pronounced bioactive properties. Quantitative analysis revealed that AEOM contains significant amounts of polyphenols (186.06 ± 0.1 mg GAE/g), flavonoids (72.3 ± 0.9 mg QE/g), and condensed tannins (4.49 ± 0.08 mg CE/g). The extract exhibited strong antioxidant activity, with an IC₅₀ value of 2.23 ± 0.03 mg/mL in the DPPH assay, and demonstrated considerable reducing power (FRAP value of 1.9 ± 0.01 mg Fe²⁺/g). Pharmacological evaluation showed that AEOM significantly reduced pain in an animal model, suggesting potential analgesic properties. Acute toxicity studies indicated no adverse effects on kidney and liver function or blood parameters at doses up to 800 mg/kg. The analgesic effect is likely mediated by flavonoids in the extract, which may inhibit pain pathways. These findings suggest that O. majorana has promising therapeutic applications, particularly as a natural analgesic agent.

Metabotropic Glutamate Receptor 5: A Potential Target for Neuropathic Pain Treatment.

Neuropathic pain, a multifaceted and incapacitating disorder, impacts a significant number of individuals globally. Despite thorough investigation, the development of efficacious remedies for neuropathic pain continues to be a formidable task. Recent research has revealed the potential of metabotropic glutamate receptor 5 (mGlu5) as a target for managing neuropathic pain. mGlu5 is a receptor present in the central nervous system that has a vital function in regulating synaptic transmission and the excitability of neurons. This article seeks to investigate the importance of mGlu5 in neuropathic pain pathways, analyze the pharmacological approach of targeting mGlu5 for neuropathic pain treatment, and review the negative allosteric mGlu5 modulators used to target mGlu5. By comprehending the role of mGlu5 in neuropathic pain, we can discover innovative treatment approaches to ease the distress endured by persons afflicted with this incapacitating ailment.

Identification of the TRPA1 cannabinoid-binding site

Chronic pain accounts for nearly two-thirds of conditions eligible for medical cannabis licenses, yet the mechanisms underlying cannabis-induced analgesia remain poorly understood. The principal phytocannabinoids, the psychoactive Δ9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD), exhibit comparable efficacy in pain management. Notably, THC functions as an agonist of cannabinoid receptor 1 (CB1), whereas CBD shows minimal activity on CB1 and CB2 receptors. Elucidating the molecular targets through which phytocannabinoids modulate the pain system is required for advancing our understanding of the pain pathway and optimizing medical cannabis therapies. Transient receptor potential ankyrin 1 (TRPA1), a pivotal chemosensor in the pain pathway, has been identified as a phytocannabinoid target. Unlike most TRPA1 activators, phytocannabinoid activation is not mediated through the electrophilic binding site, suggesting an alternative mechanism. Here, we identified the human TRPA1 channel cannabinoid-binding site (CBS) and demonstrated that mutations at residue Y840 abolished responses to both THC and CBD at saturating concentrations, indicating a shared primary binding site. Molecular modeling revealed distinct interactions of THC and CBD with the Y840 residue within the CBS. Additionally, CBD binds to the adjacent general anesthetic binding site at oversaturating concentrations. Our findings define the CBS of TRPA1 as overlapping with and adjacent to binding sites for other allosteric activators, suggesting that TRPA1 possesses a highly adaptable domain for binding non-electrophilic activators. This underscores its unique role as a chemosensor in the pain pathway. Furthermore, our results provide new insights into the molecular mechanisms of cannabinoid-induced analgesia and identify novel targets for pain management therapies.

Onabotulinumtoxin A for the Treatment of Post-Traumatic Headache: Is It Better than Anti-CGRP Antibodies?

Post-traumatic headache (PTH) is a common and debilitating consequence of traumatic brain injury (TBI), often resembling migraine and tension-type headaches. Despite its prevalence, the optimal treatment for PTH remains unclear, with current strategies largely extrapolated from other headache disorders. This review evaluates the use of onabotulinumtoxin A (ONA) and anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) in the treatment of PTH. A comprehensive literature search was conducted on PubMed, including studies published up to September 2024, focusing on the efficacy, safety, and mechanisms of onabotulinumtoxin A and anti-CGRP mAbs in PTH. Both clinical trials and observational studies were reviewed. ONA, widely recognized for its efficacy in chronic migraine, has shown limited benefits in PTH with only one trial involving abobotulinumtoxin A in a cohort of 40 subjects. A phase 2 trial with fremanezumab, an anti-CGRP monoclonal antibody, failed to demonstrate significant efficacy in PTH, raising questions about the utility of targeting CGRP in this condition. ONA may offer advantages over anti-CGRP mAbs, not only in terms of its broader mechanism of action but also in cost-effectiveness and higher patient adherence. Both ONA and anti-CGRP mAbs are potential options for the management of PTH, but the current evidence is insufficient to establish clear guidelines. The negative results from the fremanezumab trial suggest that CGRP inhibition may not be sufficient for treating PTH, whereas onabotulinumtoxin A's ability to target multiple pain pathways may make it a more promising candidate.

Targeting the Main Sources of Reactive Oxygen Species Production: Possible Therapeutic Implications in Chronic Pain.

Humans have long been combating chronic pain. In clinical practice, opioids are firstchoice analgesics, but long-term use of these drugs can lead to serious adverse reactions. Finding new, safe and effective pain relievers that are useful treatments for chronic pain is an urgent medical need. Based on accumulating evidence from numerous studies, excess reactive oxygen species (ROS) contribute to the development and maintenance of chronic pain. Some antioxidants are potentially beneficial analgesics in the clinic, but ROS-dependent pathways are completely inhibited only by scavenging ROS directly targeting cellular or subcellular sites. Unfortunately, current antioxidant treatments do not achieve this effect. Furthermore, some antioxidants interfere with physiological redox signaling pathways and fail to reverse oxidative damage. Therefore, the key upstream processes and mechanisms of ROS production that lead to chronic pain in vivo must be identified to discover potential therapeutic targets related to the pathways that control ROS production in vivo. In this review, we summarize the sites and pathways involved in analgesia based on the three main mechanisms by which ROS are generated in vivo, discuss the preclinical evidence for the therapeutic potential of targeting these pathways in chronic pain, note the shortcomings of current research and highlight possible future research directions to provide new targets and evidence for the development of clinical analgesics.

Community breast pain clinics can provide safe, quality care for women presenting with breast pain.

Breast pain is not typically a symptom of breast cancer, yet nationally 20% of 2-week wait (2WW) breast referrals are breast pain alone. The East Midlands Breast Pain Pathway improves patient experience and frees capacity in secondary care diagnostic breast clinics, managing women with breast pain only in a community setting. We report the results of implementation of community breast pain clinics (CBPCs) at sites in Derbyshire (catchment population ~1 million), with 12 months follow-up data. 1036 patients were seen at CBPCs between June 2021 and February 2023. The median patient age was 49 (range 16-88) years. 993 patients (95.8%) were discharged from the clinic with breast pain management advice. 43 (4.2%) patients were referred for further assessment at a 2WW breast diagnostic clinic. Objective family history risk assessment identified 124 patients (12.3%) above population risk of breast cancer, who were offered referral to familial cancer services for ongoing management. Seven patients were diagnosed with breast cancer at or within 12 months of CBPC attendance. Five patients were diagnosed through attending the CBPC, one patient was subsequently referred to 2WW clinic with a new symptom and had a mammographically occult tumour and one was diagnosed following a subsequent routine breast screening invitation. Two of the five patients had a personal history of breast cancer which was a stated exclusion criterion for the CBPC. Breast cancer incidence in women with breast pain only and fulfilling CBPC referral criteria was 4.8/1000, confirming that this population is at low risk of developing breast cancer.Patient service satisfaction was high with 99% (n=1022) 'extremely likely or likely' to recommend the service. The results confirm the pathway is the first to demonstrate women can be safely managed with breast pain alone in a community setting with high levels of patient satisfaction.

A patient-centric chest pain management approach utilizing a high sensitivity Troponin-I assay

ObjectiveThe purpose of this study was to assess the impact of adoption of a new cardiac chest pain pathway that included hs-cTnI in the emergency department (ED) when evaluating chest pain patients. MethodsA new pathway incorporating both hs-cTnI testing (Seimens Healthineers Atellica) and risk stratification tools was developed. The impact of the new algorithm was assessed through a retrospective observational review of patients admitted to the ED with chest pain before implementation and after implementation. Before implementation, the conventional Seimens troponin Vista assay was utilized without a defined algorithmic approach. Bivariate analyses were performed comparing the time periods to determine differences in patient discharge dispositions, length of stay, outcomes, and rate of diagnostic cardiac catheterization. ResultsThe proportion of patients discharged from the ED increased while the proportion of patients placed in observation or admitted as in-patient decreased. Variation amongst providers regarding patient disposition decreased. The stress testing rate of patients placed in observation decreased over baseline. There was no change in 30-day MACE rate, but there was a decrease in 30-day MI rate. ConclusionsThe new standardized hs-cTnI algorithm approach is safe as demonstrated by no change in 30-day MACE and is also more appropriate and efficient for patients presenting to the ED with chest pain compared to the non-standardized approach with cTnI used previously.

Physiotherapy-led care versus physician-led care for persons with low back pain: A systematic review

Objective To summarise the evidence on the effect of physiotherapy-led versus physician-led care on clinical outcomes, healthcare use, and costs in persons with low back pain. Data sources PubMed, Web of Science, CINAHL, Embase, and PEDro were systematically searched with the latest search performed in July 2024. Reference lists of articles were hand-searched. Review methods Studies comparing clinical outcomes, healthcare use, or costs between adults with low back pain first consulting a physiotherapist and those first consulting a physician were included. Methodological quality was assessed with the Newcastle-Ottawa Scale. Study design, clinical setting, patient characteristics, and group effects were extracted. Findings on outcomes assessed in two or more studies were synthesised narratively. Certainty of evidence was determined using the GRADE approach. Results Eighteen studies comprising 1,481,980 persons with low back pain were included. Most studies were non-randomised retrospective or prospective cohort studies. In primary care (15 studies), consistent evidence, though of mostly very low certainty, indicated that physiotherapy-led care leads to higher patient satisfaction, less use of medication, injections and imaging, fewer physician's visits, lower total healthcare costs, and less sick leave compared to physician-led care, without increased harm. In emergency care (three studies), evidence of very low certainty showed that physiotherapy-led care leads to shorter waiting and treatment times, and fewer hospital admissions. Conclusion Physiotherapy-led care is a clinically, time- and cost-effective care pathway for low back pain, although the certainty of evidence was overall very low. Further high-quality research with a greater focus on clinical outcomes is warranted.

Present and Future of Pharmacological Management for Acute Moderate-to-Severe Postoperative, Traumatic, or Musculoskeletal Pain in Europe: A Narrative Review.

Acute moderate-to-severe pain is common after surgery, trauma, or musculoskeletal injury, but its management remains suboptimal. Current single-agent treatments are limited by safety concerns, narrow therapeutic windows, and abuse potential, leaving substantial unmet needs. Here, we aimed to review guidelines for the management of acute moderate-to-severe post-surgical, trauma-related, or musculoskeletal pain in adults and discuss existing and potential future analgesics in this setting. We searched PubMed to identify relevant guidelines and existing analgesics for acute pain. To identify compounds in development, we searched ClinicalTrials.gov and the European Union Clinical Trials Register. Guidelines universally recognize the limitations of single-agent analgesics (particularly those with a single mechanism of action [MoA]) and recommend a multimodal approach as an established standard for acute pain. The benefit-risk profiles of traditional treatments, including paracetamol (acetaminophen), nonsteroidal anti-inflammatory drugs, selective cyclooxygenase-2 inhibitors, and opioids, can be improved by combining agents targeting different pain pathways. In multimodal approaches, lower doses of constituent agents can be used to achieve the same or superior analgesic effects relative to the individual agents. In some cases, novel formulations and co-crystal technology offer enhanced physicochemical and pharmacokinetic properties over individual agents. Lastly, initiatives to increase patient awareness and education around pain management may improve treatment satisfaction and quality of life, and hasten recovery. In conclusion, management of acute moderate-to-severe pain remains inadequate. Multimodal analgesics may offer advantages over traditional single-agent treatments (that often have a single MoA) for acute moderate-to-severe post-surgical, trauma-related, or musculoskeletal pain in adults. Multimodal analgesics, combined with patient education initiatives and non-pharmacological measures, when necessary, offer promise in addressing unmet needs in this setting.

Oxytocin shortens spreading depolarization-induced periorbital allodynia

BackgroundMigraine is among the most prevalent and burdensome neurological disorders in the United States based on disability-adjusted life years. Cortical spreading depolarization (SD) is the most likely electrophysiological cause of migraine aura and may be linked to trigeminal nociception. We previously demonstrated, using a minimally invasive optogenetic approach of SD induction (opto-SD), that opto-SD triggers acute periorbital mechanical allodynia that is reversed by 5HT1B/1D receptor agonists, supporting SD-induced activation of migraine-relevant trigeminal pain pathways in mice. Recent data highlight hypothalamic neural circuits in migraine, and SD may activate hypothalamic neurons. Furthermore, neuroanatomical, electrophysiological, and behavioral data suggest a homeostatic analgesic function of hypothalamic neuropeptide hormone, oxytocin. We, therefore, examined the role of hypothalamic paraventricular nucleus (PVN) and oxytocinergic (OXT) signaling in opto-SD-induced trigeminal pain behavior.MethodsWe induced a single opto-SD in adult male and female Thy1-ChR2-YFP transgenic mice and quantified fos immunolabeling in the PVN and supraoptic nucleus (SON) compared with sham controls. Oxytocin expression was also measured in fos-positive neurons in the PVN. Periorbital mechanical allodynia was tested after treatment with selective OXT receptor antagonist L-368,899 (5 to 25 mg/kg i.p.) or vehicle at 1, 2, and 4 h after opto-SD or sham stimulation using von Frey monofilaments.ResultsOpto-SD significantly increased the number of fos immunoreactive cells in the PVN and SON as compared to sham stimulation (p < 0.001, p = 0.018, respectively). A subpopulation of fos-positive neurons also stained positive for oxytocin. Opto-SD evoked periorbital mechanical allodynia 1 h after SD (p = 0.001 vs. sham), which recovered quickly within 2 h (p = 0.638). OXT receptor antagonist L-368,899 dose-dependently prolonged SD-induced periorbital allodynia (p < 0.001). L-368,899 did not affect mechanical thresholds in the absence of opto-SD.ConclusionsThese data support an SD-induced activation of PVN neurons and a role for endogenous OXT in alleviating acute SD-induced trigeminal allodynia by shortening its duration.

Rapid outpatient evaluationforemergency department patientswithintermediate risk chest pain safely reduces admissions.

This study aims to assess the safety of an outpatient chest pain pathway (OCPP) for patients presenting to the emergency department (ED) with chest pain and a HEART score of 4 or 5. This is a retrospective, observational, non-inferiority study assessing the impact of the OCPP on the management and outcomes of ED patients with HEART score of 4 or 5. The study compared patients evaluated in the pre-OCPP (January‒May 2018) and the post-OCPP period (January‒October 2022). Data were collected via non-blinded chart review. The primary outcome was the rate of acute myocardial infarction (AMI) and death in patients utilizing the OCPP compared to patients with HEART score 4 or 5 in 2018. Secondary outcomes included admission rates before and after the implementation of this pathway. Non-inferiority of the post-intervention study epoch for the AMI/death composite outcome was assessed via the two one-sided tests (TOST), procedure. After implementing the OCPP, rates of patients with ED HEART score of 4 or 5 admitted from the ED decreased from 85.1% (605/711) to 74.1% (1239/1671) in 2022. Of the 432 total patients discharged in 2022, 237 (54.6%) patients were referred to emergent cardiology follow-up via the OCPP. The 30-day rate of AMI/death for patients discharged via the OCPP was 0.4% (1/237), as compared to 2.2% (8/368) in 2018. When compared to rates of AMI/death for all patients with HEART score 4 or 5 in 2018, outcomes for OCPP patients were found to be non-inferior. The OCPP resulted in non-inferior rates of AMI/death in patients with HEART scores of 4 or 5 as compared to usual care.

Neuropharmacology of Neuropathic Pain: A Systematic Review.

Neuropathic pain, a debilitating condition, remains challenging to manage effectively. An insight into neuropharmacological mechanisms is critical for optimizing treatment strategies. This systematic review aims to evaluate the role of neuropharmacological agents based on their efficacy, involved neurotransmitters, and receptors. A manual literature search was undertaken in PubMed including Medline, Cochrane Library, Google Scholar, Plos One, Science Direct, and clinicaltrials.gov from 2013 until 2023. Out of the 13 included studies, seven evaluated the role of gabapentinoids. Two main drugs from this group, gabapentin and pregabalin, function by binding voltage-gated calcium channels, lowering neuronal hyperexcitability and pain signal transmission, thereby relieving neuropathic pain. Four of the pooled studies reported the use of tricyclic antidepressants (TCAs) including amitriptyline and nortriptyline which work by blocking the reuptake of norepinephrine and serotonin, their increased concentration is thought to be central to their analgesic effect. Three articles assessed the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) and reported them as effective as the TCAs in managing neuropathic pain. They work by augmenting serotonin and norepinephrine. Three studies focused on the use of selective serotonin reuptake inhibitors (SSRIs), modulating their effect by increasing serotonin levels; however, they were reported as not a highly effective treatment option for neuropathic pain. One of the studies outlined the use of cannabinoids for neuropathic pain by binding to cannabinoid receptors with only mild adverse effects. It is concluded that gabapentinoids, TCAs, and SNRIs were reported as the most effective therapy for neuropathic pain; however, for trigeminal neuralgia, anticonvulsants like carbamazepine were considered the most effective. Opioids were considered second-line drugs for neuropathic pain as they come with adverse effects and a risk of dependence. Ongoing research is exploring novel drugs like ion channels and agents modulating pain pathways for neuropathic pain management. Our review hopes to inspire further research into patient stratification by their physiology, aiding quicker and more accurate management of neuropathic pain while minimizing inadvertent side effects.

Role of Cav2.3 (R-type) Calcium Channel in Pain and Analgesia: A Scoping Review.

Voltage-gated calcium channels (VGCCs) play an important role in pain development and maintenance. As Cav2.2 and Cav3.2 channels have been identified as potential drug targets for analgesics, the participation of Cav2.3 (that gives rise to R-type calcium currents) in pain and analgesia remains incompletely understood. Identify the participation of Cav2.3 in pain and analgesia. To map research in this area as well as to identify any existing gaps in knowledge on the potential role of Cav2.3 in pain signalling, we conducted this scoping review. We searched PubMed and SCOPUS databases, and 40 articles were included in this study. Besides, we organized the studies into 5 types of categories within the broader context of the role of Cav2.3 in pain and analgesia. Some studies revealed the expression of Cav2.3 in pain pathways, especially in nociceptive neurons at the sensory ganglia. Other studies demonstrated that Cav2.3-mediated currents could be inhibited by analgesic/antinociceptive drugs either indirectly or directly. Some articles indicated that Cav2.3 modulates nociceptive transmission, especially at the pre-synaptic level at spinal sites. There are studies using different rodent pain models and approaches to reduce Cav2.3 activity or expression and mostly demonstrated a pro-nociceptive role of Cav2.3, despite some contradictory findings and deficiencies in the description of study design quality. There are three studies that reported the association of single-nucleotide polymorphisms in the Cav2.3 gene (CACNA1E) with postoperative pain and opioid consumption as well as with the prevalence of migraine in patients. Cav2.3 is a target for some analgesic drugs and has a pro-nociceptive role in pain.

A critical view: Examining disparities regarding timely cholecystectomy

BackgroundImplicit bias may prevent patients with abdominal pain from receiving optimal workup and treatment. We hypothesized that patients from socially disadvantaged backgrounds would be more likely to experience delays in receiving operative treatment for cholecystitis. To study this question, we examined factors related to having a prior emergency department presentation for abdominal pain (prior emergency department visit) within 3 months of urgent cholecystectomy. MethodsWe performed a retrospective analysis of consecutive patients who received an urgent cholecystectomy at an urban safety net public hospital between July 2019 and December 2022. The main outcome of interest was prior emergency department visit within 3 months of index cholecystectomy. We examined patient age, sex, race, ethnicity, preferred language, insurance, and employment status. Bivariate comparisons and logistic regression were used to determine the relationship between patient factors and prior emergency department visit. ResultsOf 508 cholecystectomy patients, 138 (27.2%) had a prior emergency department visit in the 3 months preceding their surgery. In bivariate analysis, younger age, Black race, Hispanic ethnicity, non-English preferred language, and type of insurance (P < .05) were associated with prior emergency department visit. In regression, younger age, Black race, Hispanic ethnicity, and having Medicare or being uninsured were associated with higher odds of having a prior emergency department visit. ConclusionMore than 1 in 4 patients had an evaluation for abdominal pain within 3 months of having an urgent cholecystectomy, and these patients were more likely to be from socially disadvantaged backgrounds. Standardized evaluation pathways for abdominal pain are needed to reduce disparities from institutional or implicit bias.

Morphine-responsive neurons that regulate mechanical antinociception.

Opioids are widely used, effective analgesics to manage severe acute and chronic pain, although they have recently come under scrutiny because of epidemic levels of abuse. While these compounds act on numerous central and peripheral pain pathways, the neuroanatomical substrate for opioid analgesia is not fully understood. By means of single-cell transcriptomics and manipulation of morphine-responsive neurons, we have identified an ensemble of neurons in the rostral ventromedial medulla (RVM) that regulates mechanical nociception in mice. Among these, forced activation or silencing of excitatory RVMBDNF projection neurons mimicked or completely reversed morphine-induced mechanical antinociception, respectively, via a brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)-dependent mechanism and activation of inhibitory spinal galanin-positive neurons. Our results reveal a specific RVM-spinal circuit that scales mechanical nociception whose function confers the antinociceptive properties of morphine.

Pain Management in Animals with Oncological Disease: Opioids as Influencers of Immune and Tumor Cellular Balance.

Advancements in understanding pain physiopathology have historically challenged animals' absence of pain senses. Studies have demonstrated that animals have comparable neural pain pathways, suggesting that cats and dogs likely experience pain similarly to humans. Understanding brain circuits for effective pain control has been crucial to adjusting pain management to the patient's individual responses and current condition. The refinement of analgesic strategies is necessary to better cater to the patient's demands. Cancer pain management searches to ascertain analgesic protocols that enhance patient well-being by minimizing or abolishing pain and reducing its impact on the immune system and cancer cells. Due to their ability to reduce nerve sensitivity, opioids are the mainstay for managing moderate and severe acute pain; however, despite their association with tumor progression, specific opioid agents have immune-protective properties and are considered safe alternatives to analgesia for cancer patients.

Natural pain killers from marine sources: a new frontier in neurosurgical pain management.

The development of new analgesics for the management of neurosurgical pain is a great opportunity in marine environments. Particular secondary metabolites with strong biological activity that have developed for defense are produced by marine bioresources. The analgesic potential of marine-derived peptides, alkaloids, terpenes and polyketides-such as discodermolide from marine sponges and ziconotide from cone snail venom-is highlighted in this letter. These substances work through novel methods that minimize the negative effects associated with conventional analgesics while focusing on particular pain pathways. Despite obstacles in sustainable sourcing and regulatory validation, the development of these marine-derived analgesics requires interdisciplinary collaboration to fulfill their potential in enhancing pain management.