To compare results from analysis of averaged and single-sweep evoked brain potentials (EPs) by visual inspection and spectral analysis in order to identify an objective measure for the analgesic effect of buprenorphine and fentanyl. Twenty-two healthy males were included in a randomized study to assess the changes in EPs after 110 sweeps of painful electrical stimulation to the median nerve following treatment with buprenorphine, fentanyl or placebo patches. Bone pressure, cutaneous heat and electrical pain ratings were assessed. EPs and pain assessments were obtained before drug administration, 24, 48, 72 and 144 h after beginning of treatment. Features from EPs were extracted by three different approaches: (i) visual inspection of amplitude and latency of the main peaks in the average EPs, (ii) spectral distribution of the average EPs and (iii) spectral distribution of the EPs from single-sweeps. Visual inspection revealed no difference between active treatments and placebo (all P > 0.05). Spectral distribution of the averaged potentials showed a decrease in the beta (12-32 Hz) band for fentanyl (P = 0.036), which however did not correlate with pain ratings. Spectral distribution in the single-sweep EPs revealed significant increases in the theta, alpha and beta bands for buprenorphine (all P < 0.05) as well as theta band increase for fentanyl (P = 0.05). For buprenorphine, beta band activity correlated with bone pressure and cutaneous heat pain (both P = 0.04, r = 0.90). In conclusion single-sweep spectral band analysis increases the information on the response of the brain to opioids and may be used to identify the response to analgesics.

Inflammatory bowel disease (IBD), encompassing Crohn’s disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30–50% of patients or cause significant side effects, emphasizing the need for new treatments. Targeting the innate immune system and enhancing drug delivery to inflamed gut regions are promising strategies. Neutrophils play a central role in IBD by releasing reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) —DNA-based structures with cytotoxic proteins—that contribute to mucosal damage and inflammation. Recent studies linking ROS production, DNA repair, and NET formation have identified NETs as potential therapeutic targets, with preclinical models showing positive outcomes from NET inhibition. Innovative oral drug delivery systems designed to target gut inflammation directly—without systemic absorption—could improve treatment precision and reduce side effects. Advanced formulations utilize properties such as particle size, surface modifications, and ROS-triggered release to selectively target the distal ileum and colon. A dual strategy that combines a deeper understanding of IBD pathophysiology to identify inflammation-related therapeutic targets with advanced drug delivery systems may offer significant promise. For instance, pairing NET inhibition with ROS-responsive nanocarriers could enhance treatment efficacy, though further research is needed. This synergistic approach has the potential to greatly improve outcomes for IBD patients.

During the last decades there has been a tremendous development of non-invasive methods for assessment of brain activity following visceral pain. Improved methods for neurophysiological and brain imaging techniques have vastly increased our understanding of the central processing of gastrointestinal sensation and pain in both healthy volunteers as well as in patients suffering from gastrointestinal disorders. The techniques used are functional magnetic resonance imaging (fMRI), positron emission tomography (PET), electroencephalography (EEG)/evoked brain potentials (EPs), magnetoencephalography (MEG), single photon emission computed tomography (SPECT), and the multimodal combinations of these techniques. The use of these techniques has brought new insight into the complex brain processes underlying pain perception, including a number of subcortical and cortical regions, and paved new ways in our understanding of acute and chronic pain. The pathways are dynamic with a delicate balance between facilitatory and inhibitory pain mechanisms, and with modulation of the response to internal or external stressors with a high degree of plasticity. Hence, the ultimate goal in imaging of pain is to follow the stimulus response throughout the neuraxis. Brain activity measured by fMRI is based on subtracting regional changes in blood oxygenation during a resting condition from the signal during a stimulus condition, and has high spatial resolution but low temporal resolution. SPECT and PET are nuclear imaging techniques where radiolabeled molecules are injected with visualization of the distribution, density and activity of receptors in the brain allowing not only assessment of brain activity but also study of receptor sites. EEG is based on assessment of electrical activity in the brain, and recordings of the resting EEG and evoked potentials following an external stimulus are used to study normal visceral pain processing, alterations of pain processing in different patient groups and the effect of pharmacological intervention. EEG has high temporal resolution, but relative poor spatial resolution, which however to some extent can be overcome by applying inverse modelling algorithms and signal decomposition procedures. MEG is based on recording the magnetic fields produced by electrical currents in the brain, has high spatial resolution and is especially suitable for the study cortical activation. The treatment of chronic abdominal pain is often ineffective and dissapointing, which leads to search for optimized treatment achieved on the basis of a better understanding of underlying pain mechanisms. Application of the recent improvements in neuroimaging on the visceral pain system may likely in near future contribute substantially to our understanding of the functional and structural pathophysiology underlying chronic visceral pain disorders, and pave the road for optimized individual and mechanism based treatments. The purpose of this review is to give a state-of-the-art overview of these methods, with focus on EEG, and especially the advantages and limitations of the single methods in clinical gastrointestinal pain esearch including examples from relevant studies.

Background. Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a complex inflammatory condition affecting the intestinal tract. Currently, immune-modulating treatments are inadequate for 30–50% of patients and often cause significant side effects, highlighting the urgent need for a personalized medicine approach. Real-world data and archived gut biological material from clinical repositories could be a resource for identifying new drug candidates and biomarkers. This study assesses the extent of stored formalin-fixed, paraffin-embedded (FFPE) gut biopsies from patients with IBD that could be leveraged for research efforts. Methods. Data from the Danish National Patient Register and the Danish Pathology Register were used to construct a cohort of patients diagnosed with IBD between 1 January 2005, and 30 June 2013, and followed for five years. Results. Among 14,512 IBD patients, 13,936 (96%) had at least one biopsy visit within five years after their initial diagnosis (CD 94%, UC 97%), and 13,598 (94%) had their first biopsy visit as part of the diagnostic process. Biopsies were taken from the colon (82%) or multiple locations (46%). Patients with severe disease had more biopsy visits than those with non-severe disease (IBD 3.3 vs. 2.0 visits, CD 2.9 vs. 1.9 visits, UC 3.6 vs. 2.0 visits). Conclusions. Thus, the vast majority of patients with IBD have biopsies taken. These findings demonstrate the feasibility and applicability of combining real-world data and archived gut biopsies for research, highlighting it as a valuable but underutilized resource for identifying new drug candidates and biomarkers, with huge potential for enhancing personalized medicine within IBD for the benefit of patients and society.

Despite considerable progress in pain management, recommended systemic pharmacotherapy often comes with a high risk of serious side effects adversely affecting quality of life. Hence, topical routes of drug administration are currently gaining popularity in painful conditions such as diabetic peripheral neuropathy. Voltage-gated sodium channels (Nav) are expressed in peripheral nerves and are crucial for development and maintenance of neuropathic pain. Subtypes Nav1.7, 1.8, and 1.9 are highly expressed in nociceptors and are therefore interesting targets for topical pharmacotherapeutics. The aim of this study was to assess pharmacologically modulated excitability of peripheral sensory nerves using the human experimental perception threshold tracking technique, an indirect method for measuring the excitability of peripheral nerves. This randomized, placebo-controlled, and double-blinded study included 20 healthy participants. A novel electrical stimulation protocol—the Sodium channel Excitability Nociceptor Testing protocol—was used to identify alterations in Nav1.7, 1.8, and 1.9 after applying 3 (5% lidocaine, 10% phenytoin, and 2% mepyramine) topical pharmacological drugs. There was a significant difference in the relative increase in the perception threshold after drug application between drugs ( P < 0.01) and between drugs and placebo ( P < 0.01), except for phenytoin ( P = 0.22). The computational model suggests that lidocaine and mepyramine caused different alterations of the Nav1.7, 1.8, and 1.9 currents. The Sodium channel Excitability Nociceptor Testing protocol can be used to investigate differential pharmacological alterations of specific Nav subtypes. This may lead to better insight of neurophysiological mechanisms of sensory afferents, forming the basis for targeted drug development, leading the way to stratified treatment regimens of peripheral pain.