Effect of N-palmitoylethanolamine-oxazoline on comorbid neuropsychiatric disturbance associated with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic disorder characterized by inflammation of the gastrointestinal (GI) tract, and it is associated with different neurological disorders. Recent evidence has demonstrated that the gut-brain-axis has a central function in the perpetuation of IBS, and for this reason, it can be considered a possible therapeutic target. N-Palmitoylethanolamine-oxazoline (PEA-OXA) possesses anti-inflammatory and potent neuroprotective effects. Although recent studies have explained the neuroprotective properties of PEA-OXA, nothing is known about its effects on the gut-brain axis during colitis. The aim of this study is to explore the mechanism and the effect of PEA-OXA on the gut-brain axis in rats subjected to experimental colitis induced by oral administration of dextran sulfate sodium (DSS). Daily oral administration of PEA-OXA (10 mg/kg daily o.s.) was able to decrease the body weight loss, macroscopic damage, colon length, histological alteration, and inflammation after DSS induction. Additionally, PEA-OXA administration enhanced neurotrophic growth factor release and decreased the astroglial and microglial activation induced by DSS. Moreover, PEA-OXA restored intestinal permeability and tight junctions (TJs) as well as reduced apoptosis in the colon and brain. In our work, we demonstrated, for the first time, the action of PEA-OXA on the gut-brain axis in a model of DSS-induced colitis and its implication on the "secondary" effects associated with colonic disturbance.

The neuroprotective effects of micronized PEA (PEA-m) formulation on diabetic peripheral neuropathy in mice.

Diabetic peripheral neuropathy (DPN) is a complication of diabetes connected with morbidity and mortality. DPN presents deterioration of peripheral nerves with pain, feebleness, and loss of sensation. Particular medications might display their remedial potential by controlling neuroinflammation. Palmitoylethanolamide (PEA) is an autacoid local injury antagonist distinguished for its neuroprotective, analgesic, and anti-inflammatory properties in numerous experimental models of neuroinflammation. Based on these findings, the goal of this work was to better test the neuroprotective effects of a formulation of micronized PEA (PEA-m) and the probable mechanism of action in a mouse model of DPN induced by streptozotocin (STZ) injection. Diabetic and control animals received PEA-m (10 mg/kg) by oral gavage daily starting 2 wk from STZ injection. After 16 wk, the animals were euthanized, and blood, urine, spinal cord, and sciatic nerve tissues were collected. Our results demonstrated that after diabetes induction, PEA-m was able to reduce mechanical, thermal hyperalgesia, and motor alterations as well as reduce mast cell activation and nerve growth factor expression. In addition, PEA-m decreased neural histologic damage, oxidative and nitrosative stress, cytokine release, angiogenesis, and apoptosis. Moreover, spinal microglia activation (IBA-1), phospho-P38 MAPK, and nuclear factor NF-κB inflammatory pathways were also inhibited. The protective effects of PEA-m could be correlated at least in part to peroxisome proliferator-activated receptor-α activation. In summary, we demonstrated that PEA-m represents a new therapeutic strategy for neuroinflammation pain associated with mixed neuropathies.-Impellizzeri, D., Peritore, A. F., Cordaro, M., Gugliandolo, E., Siracusa, R., Crupi, R., D'Amico, R., Fusco, R., Evangelista, M., Cuzzocrea, S., Di Paola, R. The neuroprotective effects of micronized PEA (PEA-m) formulation on diabetic peripheral neuropathy in mice.

The Protective Effects of Pre- and Post-Administration of Micronized Palmitoylethanolamide Formulation on Postoperative Pain in Rats.

BACKGROUND: Postoperative pain (PO) is a common form of acute pain. Inadequate PO treatment is an important health problem, as it leads to worse outcomes, such as chronic post-surgical pain. Therefore, it is necessary to acquire new knowledge on PO mechanisms to develop therapeutic options with greater efficacy than those available today and to lower the risk of adverse effects. For this reason, we evaluated the ability of micronized palmitoylethanolamide (PEA-m) to resolve the pain and inflammatory processes activated after incision of the hind paw in an animal model of PO. METHODS: The animals were subjected to surgical paw incision and randomized into different groups. PEA-m was administered orally at 10 mg/kg at different time points before or after incision. RESULTS: Our research demonstrated that the pre- and post-treatment with PEA-m reduced the activation of mast cells at the incision site and the expression of its algogenic mediator nerve growth factor (NGF) in the lumbar spinal cord. Furthermore, again at the spinal level, it was able to decrease the activation of phospho-extracellular signal-regulated kinases (p-ERK), ionized calcium binding adaptor molecule 1 (Iba1), glial fibrillary acidic protein (GFAP), and the expression of brain-derived neurotrophic factor (BDNF). PEA-m also reduced the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) spinal pathway, showing a protective effect in a rat model of PO. CONCLUSION: The results obtained reinforce the idea that PEA-m may be a potential treatment for the control of pain and inflammatory processes associated with PO. In addition, pre- and post-treatment with PEA-m is more effective than treatment alone after the surgery and this limits the time of taking the compound and the abuse of analgesics.

Short-latency afferent inhibition and somato-sensory evoked potentials during the migraine cycle: surrogate markers of a cycling cholinergic thalamo-cortical drive?

BACKGROUND: Short-latency afferent inhibition (SAI) consists of motor cortex inhibition induced by sensory afferents and depends on the excitatory effect of cholinergic thalamocortical projections on inhibitory GABAergic cortical networks. Given the electrophysiological evidence for thalamo-cortical dysrhythmia in migraine, we studied SAI in migraineurs during and between attacks and searched for correlations with somatosensory habituation, thalamocortical activation, and clinical features. METHODS: SAI was obtained by conditioning the transcranial magnetic stimulation-induced motor evoked potential (MEP) with an electric stimulus on the median nerve at the wrist with random stimulus intervals corresponding to the latency of individual somatosensory evoked potentials (SSEP) N20 plus 2, 4, 6, or 8 ms. We recruited 30 migraine without aura patients, 16 between (MO), 14 during an attack (MI), and 16 healthy volunteers (HV). We calculated the slope of the linear regression between the unconditioned MEP amplitude and the 4-conditioned MEPs as a measure of SAI. We also measured SSEP amplitude habituation, and high-frequency oscillations (HFO) as an index of thalamo-cortical activation. RESULTS: Compared to HV, SAI, SSEP habituation and early SSEP HFOs were significantly reduced in MO patients between attacks, but enhanced during an attack. There was a positive correlation between degree of SAI and amplitude of early HFOs in HV, but not in MO or MI. CONCLUSIONS: The migraine cycle-dependent variations of SAI and SSEP HFOs are further evidence that facilitatory thalamocortical activation (of GABAergic networks in the motor cortex for SAI), likely to be cholinergic, is reduced in migraine between attacks, but increased ictally.

N-Palmitoylethanolamine-oxazoline (PEA-OXA): A new therapeutic strategy to reduce neuroinflammation, oxidative stress associated to vascular dementia in an experimental model of repeated bilateral common carotid arteries occlusion.

AIM: Recent studies revealed that pharmacological modulation of NAE-hydrolyzing acid amidase (NAAA) can be achieved with PEA oxazoline (PEA-OXA). Hence, the aim of the present work was to thoroughly evaluate the anti-inflammatory and neuroprotective effects of PEA-OXA in an experimental model of vascular dementia (VaD) induced by bilateral carotid arteries occlusion. At 24 h after VaD induction, animals were orally administered with 10 mg/kg of PEA-OXA daily for 15 days. RESULTS: Brain tissues were handled for histological, immunohistochemical, western blot, and immunofluorescence analysis. PEA-OXA treatment evidently reduced the histological alterations and neuronal death induced by VaD and additionally improved behavioral deficits. Further, PEA-OXA decreased GFAP and Iba-1, markers of astrocytes, and microglia activation, as well as increased MAP-2, a marker of neuron development. Moreover, PEA-OXA reduced oxidative stress, modulated Nrf2-mediated antioxidant response, and inhibited the apoptotic process. INNOVATION: Some drugs may demonstrate their healing potential by regulating neuroinflammation, rather than by their habitually attributed actions only. Palmitoylethanolamide (PEA) is a prototype ALIAmide, well-known for its analgesic, anti-inflammatory, and neuroprotective properties. The inhibition of PEA degradation by targeting NAAA, its catabolic enzyme, is a different approach for treating neuroinflammation. This research offers new insight into the mechanism of PEA-OXA-induced neuroprotection. CONCLUSION: Thus, the modulation of intracellular NAAA by PEA-OXA could offer a novel means of controlling neuroinflammatory conditions associated with VaD.

Resting state connectivity between default mode network and insula encodes acute migraine headache.

Background Previous functional MRI studies have revealed that ongoing clinical pain in different chronic pain syndromes is directly correlated to the connectivity strength of the resting default mode network (DMN) with the insula. Here, we investigated seed-based resting state DMN-insula connectivity during acute migraine headaches. Methods Thirteen migraine without aura patients (MI) underwent 3 T MRI scans during the initial six hours of a spontaneous migraine attack, and were compared to a group of 19 healthy volunteers (HV). We evaluated headache intensity with a visual analogue scale and collected seed-based MRI resting state data in the four core regions of the DMN: Medial prefrontal cortex (MPFC), posterior cingulate cortex (PCC), and left and right inferior parietal lobules (IPLs), as well as in bilateral insula. Results Compared to HV, MI patients showed stronger functional connectivity between MPFC and PCC, and between MPFC and bilateral insula. During migraine attacks, the strength of MPFC-to-insula connectivity was negatively correlated with pain intensity. Conclusion We show that greater subjective intensity of pain during a migraine attack is associated with proportionally weaker DMN-insula connectivity. This is at variance with other chronic extra-cephalic pain disorders where the opposite was found, and may thus be a hallmark of acute migraine head pain.

A novel composite formulation of palmitoylethanolamide and quercetin decreases inflammation and relieves pain in inflammatory and osteoarthritic pain models.

BACKGROUND: Osteoarthritis (OA) is a common progressive joint disease in dogs and cats. The goal of OA treatment is to reduce inflammation, minimize pain, and maintain joint function. Currently, non-steroidal anti-inflammatory drugs (e.g., meloxicam) are the cornerstone of treatment for OA pain, but side effects with long-term use pose important challenges to veterinary practitioners when dealing with OA pain. Palmitoylethanolamide (PEA) is a naturally-occurring fatty acid amide, locally produced on demand by tissues in response to stress. PEA endogenous levels change during inflammatory and painful conditions, including OA, i.e., they are typically increased during acute conditions and decreased in chronic inflammation. Systemic treatment with PEA has anti-inflammatory and pain-relieving effects in several disorders, yet data are lacking in OA. Here we tested a new composite, i.e., PEA co-ultramicronized with the natural antioxidant quercetin (PEA-Q), administered orally in two different rat models of inflammatory and OA pain, namely carrageenan paw oedema and sodium monoiodoacetate (MIA)-induced OA. Oral treatment with meloxicam was used as benchmark. RESULTS: PEA-Q decreased inflammatory and hyperalgesic responses induced by carrageenan injection, as shown by: (i) paw oedema reduction, (ii) decreased severity in histological inflammatory score, (iii) reduced activity of myeloperoxidase, i.e., a marker of inflammatory cell infiltration, and (iv) decreased thermal hyperalgesia. Overall PEA-Q showed superior effects compared to meloxicam. In MIA-treated animals, PEA-Q exerted the following effects: (i) reduced mechanical allodynia and improved locomotor function, (ii) protected cartilage against MIA-induced histological damage, and (iii) counteracted the increased serum concentration of tumor necrosis factor alpha, interleukin 1 beta, metalloproteases 1, 3, 9 and nerve growth factor. The magnitude of these effects was comparable to, or even greater than, those of meloxicam. CONCLUSION: The present findings shed new light on some of the inflammatory and nociceptive pathways and mediators targeted by PEA-Q and confirm its anti-inflammatory and pain-relieving effects in rodent OA pain models. The translatability of these observations to canine and feline OA pain is currently under investigation.

Anodal transcranial direct current stimulation over the left temporal pole restores normal visual evoked potential habituation in interictal migraineurs.

BACKGROUND: Neuroimaging data has implicated the temporal pole (TP) in migraine pathophysiology; the density and functional activity of the TP were reported to fluctuate in accordance with the migraine cycle. Yet, the exact link between TP morpho-functional abnormalities and migraine is unknown. Here, we examined whether non-invasive anodal transcranial direct current stimulation (tDCS) ameliorates abnormal interictal multimodal sensory processing in patients with migraine. METHODS: We examined the habituation of visual evoked potentials and median nerve somatosensory evoked potentials (SSEP) before and immediately after 20-min anodal tDCS (2 mA) or sham stimulation delivered over the left TP in interictal migraineurs. RESULTS: Prior to tDCS, interictal migraineurs did not exhibit habituation in response to repetitive visual or somatosensory stimulation. After anodal tDCS but not sham stimulation, migraineurs exhibited normal habituation responses to visual stimulation; however, tDCS had no effect on SSEP habituation in migraineurs. CONCLUSION: Our study shows for the first time that enhancing excitability of the TP with anodal tDCS normalizes abnormal interictal visual information processing in migraineurs. This finding has implications for the role of the TP in migraine, and specifically highlights the ventral stream of the visual pathway as a pathophysiological neural substrate for abnormal visual processing in migraine.

Clinical management of osteoporotic vertebral fracture treated with percutaneous vertebroplasty.

Our study demonstrated percutaneous vertebroplasty (PVP) is an effective procedure to rapidly reduce back pain in patients affected by acute osteoporotic vertebral compression fractures (OVCFs) assessed by MRI. We confirmed in our sample, femoral bone density impacts more deeply than vertebral T-score and/or BMD on bone strenght, as it is less affected by any interferences. We interestingly found the presence of previous osteoporotic fragility fractures and chronic glucocorticoids therapy should especially negatively influence bone health of our patients. On the other hand, even if both FRAX scores for major osteoporotic fractures and for femoral fractures seemed to globally define a population at major risk for fragility fractures, our analysis is retrospectively done. We choose and suggest a multidisciplinary medical management of these patients, considering OP is a multifactorial disease and OVCFs usually produce lots of different important consequences on general health.

Lateral inhibition in the somatosensory cortex during and between migraine without aura attacks: Correlations with thalamocortical activity and clinical features.

BACKGROUND: We studied lateral inhibition in the somatosensory cortex of migraineurs during and between attacks, and searched for correlations with thalamocortical activity and clinical features. PARTICIPANTS AND METHODS: Somatosensory evoked potentials (SSEP) were obtained by electrical stimulation of the right median (M) or ulnar (U) nerves at the wrist or by simultaneous stimulation of both nerves (MU) in 41 migraine without aura patients, 24 between (MO), 17 during attacks, and in 17 healthy volunteers (HVs). We determined the percentage of lateral inhibition of the N20-P25 component by using the formula [(100)-MU/(M + U)*100]. We also studied high-frequency oscillations (HFOs) reflecting thalamocortical activation. RESULTS: In migraine, both lateral inhibition (MO 27.9% vs HVs 40.2%; p = 0.009) and thalamocortical activity (MO 0.5 vs HVs 0.7; p = 0.02) were reduced between attacks, but not during. In MO patients, the percentage of lateral inhibition negatively correlated with days elapsed since the last migraine attack (r = -0.510, p = 0.01), monthly attack duration (r = -0.469, p = 0.02) and severity (r = -0.443, p = 0.03), but positively with thalamocortical activity (r = -0.463, p = 0.02). CONCLUSIONS: We hypothesize that abnormal migraine cycle-dependent dynamics of connectivity between subcortical and cortical excitation/inhibition networks may contribute to clinical features of MO and recurrence of attacks.

Cortical functional correlates of responsiveness to short-lasting preventive intervention with ketogenic diet in migraine: a multimodal evoked potentials study.

BACKGROUND: Here, we aim to identify cortical electrofunctional correlates of responsiveness to short-lasting preventiveintervention with ketogenic diet (KD) in migraine. METHODS: Eighteen interictal migraineurs underwent visual (VEPs) and median nerve somatosensory (SSEPs) evokedpotentials before and after 1 month of KD during ketogenesis. We measured VEPs N1-P1 and SSEPs N20-P25 amplitudes respectively in six and in two sequential blocks of 100 sweeps as well as habituation as theslope of the linear regression between block 1 to 6 for VEPs or between 1 to 2 for SSEPs. RESULTS: After 1-month of KD, a significant reduction in the mean attack frequency and duration was observed (all P< 0.001). The KD did not change the 1st SSEP and VEP block of responses, but significantly inducednormalization of the interictally reduced VEPs and SSEPs (all p < 0.01) habituation during the subsequentblocks. CONCLUSIONS: KD could restore normal EPs habituation curves during stimulus repetition without significantly changing theearly amplitude responses. Thus, we hypothesize that KD acts on habituation regulating the balancebetween excitation and inhibition at the cortical level.

Fentanyl Buccal Tablet: A New Breakthrough Pain Medication in Early Management of Severe Vaso-Occlusive Crisis in Sickle Cell Disease.

BACKGROUND: Sickle cell disease (SCD) is a worldwide distributed hereditary red cell disorder. The principal clinical manifestations of SCD are the chronic hemolytic anemia and the acute vaso-occlusive crisis (VOCs), which are mainly characterized by ischemic/reperfusion tissue injury. Pain is the main symptom of VOCs, and its management is still a challenge for hematologists, requiring a multidisciplinary approach. METHODS: We carried out a crossover study on adult SCD patients, who received two different types of multimodal analgesia during two separate severe VOCs with time interval between VOCs of at least 6 months. The first VOC episode was treated with ketorolac (0.86 mg/kg/day) and tramadol (7.2 mg/kg/day) (TK treatment). In the second VOC episode, fentanyl buccal tablet (FBT; 100 µg) was introduced in a single dose after three hours from the beginning of TK analgesia (TKF treatment). We focused on the first 24 hours of acute pain management. The primary efficacy measure was the time-weighted-sum of pain intensity differences (SPID24). The secondary efficacy measures included the pain intensity difference (PID), the total pain relief (TOTPAR), and the time-wighted sum of anxiety (SAID24). RESULTS: SPID24 was significantly higher in TKF than in TK treatment. All the secondary measures were significantly ameliorated in TKF compared to TK treatment, without major opioid side effects. Patients satisfaction was higher with TKF treatment than with TK one. CONCLUSIONS: We propose that VOCs might require breakthrough pain drug strategy as vaso-occlusive phenomena and enhanced vasoconstriction promoting acute ischemic pain component exacerbate the continuous pain of VOCs. FBT might be a powerful and feasible tool in early management of acute pain during VOCs in emergency departments.

The Pharmacological Treatment of Chronic Pain: From Guidelines to Daily Clinical Practice.

In agreement with the International Association for the Study of Pain, chronic pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. To date, there are several types of pain: nociceptive, neuropathic, and nociplastic. In the present narrative review, we evaluated the characteristics of the drugs used for each type of pain, according to guidelines, and their effects in people with comorbidity to reduce the development of severe adverse events.

Molecular targets for anti-oxidative protection of açaí berry against diabetes myocardial ischemia/reperfusion injury.

Myocardial ischemia/reperfusion injury (MIRI) is the principal cause of death and occurs after prolonged blockage of the coronary arteries. Diabetes represents one of the main factors aggravating myocardial injury. Restoring blood flow is the first intervention against a heart attack, although reperfusion process could cause additional damage, such as the overproduction of reacting oxygen species (ROS). In recent years, açaí berry has gained international attention as a functional food due to its antioxidant and anti-inflammatory properties; not only that but this fruit has shown glucose-lowering effects. Therefore, this study was designed to evaluate the cardioprotective effects of açaí berry on the inflammatory and oxidative responses associated with diabetic MIRI. Diabetes was induced in rats by a single intravenous inoculation of streptozotocin (60 mg/kg) and allowed to develop for 60 days. MIRI was induced by occlusion of the left anterior descending coronary artery for 30 min followed by 2 h of reperfusion. Açaí (200 mg/kg) was administered 5 min before the end of ischemia and 1 h after reperfusion. In this study, we clearly demonstrated that açaí treatment was able to reduce biomarkers of myocardial damage, infarct size, and apoptotic process. Moreover, açaí administrations reduced inflammatory and oxidative response, modulating Nf-kB and Nrf2 pathways. These results suggest that açai berry supplementation could represent a useful strategy for pathological events associated to MIRI.

What Is the Role of Palmitoylethanolamide Co-Ultramicronized with Luteolin on the Symptomatology Reported by Patients Suffering from Long COVID? A Retrospective Analysis Performed by a Group of General Practitioners in a Real-Life Setting.

Long COVID is a recognized post-viral syndrome characterized by neurological, somatic and neuropsychiatric symptoms that might last for long time after SARS-CoV-2 infection. An ever-growing number of patients come to the observation of General Practitioners complaining of mild or moderate symptoms after the resolution of the acute infection. Nine General Practitioners from the Rome area (Italy) performed a retrospective analysis in order to evaluate the role of the supplementation with Palmitoylethanolamide co-ultramicronized with Luteolin (PEALUT) on neurologic and clinical symptoms reported by their patients after COVID-19 resolution. Supplementation with PEALUT helped to improve all patient-reported symptoms, especially pain, anxiety and depression, fatigue, brain fog, anosmia and dysgeusia, leading to an overall improvement in patients' health status. To our knowledge these are the first data presented on Long COVID patients collected in a territorial setting. Despite their preliminary nature, these results highlight the pathogenetic role of "non-resolving" neuroinflammation in Long COVID development and consequently the importance of its control in the resolution of the pathology and put the focus on the General Practitioner as the primary figure for early detection and management of Long COVID syndrome in a real-life setting. Future randomized, controlled, perspective clinical trials are needed to confirm this preliminary observation.

Metabolomics and Microbiomics: New Potential Strategies in Chronic Pain Syndrome.

Chronic pain affects almost 20% of the European adult population and it significantly reduces patients' quality of life. Chronic pain is considered a multidimensional experience determined by the interaction of several genetic and environmental factors. The effect of specific genetic contributions is often unclear, and the interpretation of the results from studies focused on genetic influences on pain has been complicated by the existence of multiple pain phenotypes. A step forward from genetics could be given by the application of metabolomics and microbiomics tools. Metabolomics is a powerful approach for hypothesis generation in biology, and it aims to analyze low molecular weight compounds, either metabolic intermediates or metabolic end-products, resulting from human or microbial metabolism. Microbiomics is a fast-growing field in which all the microbes are examined together, and as a result, its perturbation may indicate the development of chronic diseases. By applying these methodologies for the study of chronic pain, several differences have been identified. The alteration of the choline-PAF pathway is an intriguing finding recognized by several groups. In our opinion, metabolomics and microbiomics techniques will allow significant progress into the medical field. Patients may benefit from the possibility of being stratified and classified based on their metabolic and microbial profile, which, in the next future, may lead to personalized therapy.

Basic guide to chronic pain assessment: from neurophysiology to bedside.

Chronic musculoskeletal pain is a highly prevalent condition that is commonly encountered in both general and specialist practice. Nonetheless, it still represents a significant challenge to the practitioners because of the lack of substantial evidence-based guidance. This review aimed to summarize the main pathophysiological mechanisms of chronic pain offering a mechanism-oriented approach to diagnosis and management. We believe that a basic knowledge of the physical signs and symptoms of these mechanisms could empower the clinician to choose appropriate medication and identify high-risk pain patients. Central sensitization and neuropathic features may arise in previously nociceptive and inflammatory pain syndromes. Central sensitization is a functional remodeling of the spinal cord, where light touch afferents are recruited by nociceptive second-order neurons. Neuropathic features include both negative signs, such as reduced perception of vibration and touch, and positive symptoms, such as paroxysmal electric shock pain, due to ectopic discharge. These phenomena are the neurobiological basis of the commonly defined refractory chronic pain. Early detection and specific treatment of these mechanisms are required in order to restrain the reinforcement of pronociceptive remodeling of the nervous system.

Nurses' Behavior Regarding Pain Treatment in an Emergency Department: A Single-Center Observational Study.

PURPOSE: The aim of this prospective study was to assess the behavior of emergency department (ED) nurses with regard to pain and their role in pain management in a real-life clinical setting. METHODS: A total of 509 consecutive patients were enrolled during a 6-week period. A case-report form was used to collect data on nurses' approaches to pain, time to analgesia provision, and patient-perceived quality of analgesia. RESULTS: Triage nurses actively inquired about pain in almost every case, but they did not estimate pain intensity in a third of patients. In the majority of cases, triage nurses did not report pain-related findings to the physician, who was the only professional that could prescribe analgesia to patients. The assignment of the color-coding of triage by nurses appears to be related to the perceived severity of the clinical case and a more comprehensive evaluation of pain. More than half of patients were at least fairly satisfied with analgesia. CONCLUSION: Pain is increasingly screened during triage, but its comprehensive assessment and management still lack systematic application. We believe that further education and implementation of analgesia protocols may empower nurses to manage ED patients' pain more effectively and in a more timely manner.