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Recent findings indicate that nociceptive nerves are not "free", but similar to touch and pressure sensitive nerves, terminate in an end-organ in mice. This sensory structure consists of the nociceptive nerves and specialized nociceptive Schwann cells forming a mesh-like organ in subepidermis with pain transduction initiated at both these cellular constituents. The intimate relation of nociceptive nerves with nociceptive Schwann cells in mice raises the question whether defects in nociceptive Schwann cells can by itself contribute to pain hyperalgesia, nerve retraction, and peripheral neuropathy. We therefore examined the existence of nociceptive Schwann cells in human skin and their possible contribution to neuropathy and pain hyperalgesia in mouse models. Similar to mouse, human skin contains SOX10+/S100B+/AQP1+ Schwann cells in the subepidermal border that have extensive processes, which are intimately associated with nociceptive nerves projecting into epidermis. The ablation of nociceptive Schwann cells in mice resulted in nerve retraction and mechanical, cold, and heat hyperalgesia. Conversely, ablating the nociceptive nerves led to a retraction of epidermal Schwann cell processes, changes in nociceptive Schwann cell soma morphology, heat analgesia, and mechanical hyperalgesia. Our results provide evidence for a nociceptive sensory end-organ in the human skin and using animal models highlight the interdependence of the nerve and the nociceptive Schwann cell. Finally, we show that demise of nociceptive Schwann cells is sufficient to cause neuropathic-like pain in the mouse.
Learn More >Our study aims to assess improvement with symptomatic treatment of pain-related functional gastrointestinal disorders (FGIDs) in a biopsychosocial construct and evaluate validity of Rome III criteria. Children with chronic abdominal pain diagnosed with an FGID or organic disease were followed for 1 year: 256/334 were diagnosed with an FGID and 78/334 were diagnosed with a possible organic disease due to alarm signs or not meeting Rome III criteria. After 1 year, 251 had true FGID and 46 had organic diseases. Ninety percent of FGID patients improved with symptomatic treatment over an average of 5.4 months. With a 95% confidence interval, Rome criteria predicted FGIDs with sensitivity 0.89, specificity 0.90, positive predictive value 0.98, and negative predictive value 0.59. We conclude that symptomatic treatment of pain-related FGIDs results in clinical improvement and could reduce invasive/expensive testing. Rome III criteria's high specificity and positive predictive value suggest they can rule in a diagnosis of FGID.
Learn More >Quantitative objective measurement of chronic pain is important. We elucidated chronic pain-related cortical neural activity and neural connectivity among pain-related brain regions in complex regional pain syndrome (CRPS). Resting-state magnetoencephalography recordings were performed. Cortical current density and neural connectivity, revealed by amplitude envelope correlation (AEC), were estimated on standardized brain magnetic resonance imaging. Intra-experiment pain was assessed subjectively using a visual analogue scale (VAS). The correlation between current density and VAS scores was calculated for the occipital areas and pain-related cortices. Current density in the primary (SI) and secondary (SII) somatosensory cortex and precuneus in both hemispheres was negatively correlated with the pain VAS score. The AEC and VAS values were significantly correlated for the SII and the precuneus and for the SII and insular cortex in the alpha frequency band in the right hemisphere. In the theta frequency band, the AEC and VAS values correlated for the SII and posterior cingulate cortex in the right hemisphere. Our results suggested that disruption of pain processes and functions in the default mode network occurs in CRPS. Our method targeting the neural mechanism of pain has the potential to offer a clinically objective means of evaluating it.
Learn More >Platelet-activating factor (PAF) is a potent proinflammatory phospholipid mediator that elicits various cellular functions and promotes several pathological events, including anaphylaxis and neuropathic pain. PAF is biosynthesized by two types of lyso-PAF acetyltransferases: lysophosphatidylcholine acyltransferase 1 (LPCAT1) and LPCAT2, which are constitutive and inducible forms of lyso-PAF acetyltransferase, respectively. Because LPCAT2 mainly produces PAF under inflammatory stimuli, understanding the structure of LPCAT2 is important for developing specific drugs against PAF-related inflammatory diseases. Although the structure of LPCAT2 has not been determined, the crystal structure was reported for Thermotoga maritima PlsC, an enzyme in the same gene family as LPCAT2. Here, we identified residues in mouse LPCAT2 essential for its enzymatic activity and a potential acyl-coenzyme A (CoA)-binding pocket, based on homology modeling of mouse LPCAT2 with PlsC. We also found that Ala115 of mouse LPCAT2 was important for acyl-CoA selectivity. In conclusion, these results predict the three-dimensional (3D) structure of mouse LPCAT2. Our findings have implications for the future development of new drugs against PAF-related diseases.
Learn More >A subset of patients with chronic pain who receive exposure in vivo (EXP) treatment experience clinically relevant relief of pain intensity. Although pain relief is not an explicit therapeutic target, it is important to understand how and why this concomitant effect occurs in some patients but not others. This longitudinal study therefore aimed to characterize brain plasticity as well as to explore pretreatment factors related to pain relief.
Learn More >We conducted a systematic review/meta-analysis to evaluate noninvasive brain stimulation (NIBS) efficacy to alleviate pain and improve disability in low back pain (LBP).
Learn More >In Denmark the boundaries between cannabis as an illicit drug and licit medicine have shifted rapidly in recent years, affecting also policy. However, the vast majority of Danes, who use cannabis as medicine (CaM) continue to rely on the unregulated market for supply. This study explores patterns of use and motives for use of CaM in Denmark.
Learn More >Social deprivation is associated with a higher prevalence of chronic pain in children and an under-representation in specialist paediatric chronic pain programs. Our primary objective was to determine if there was a relationship between social deprivation and paediatric chronic pain referrals in Ireland. Secondary objectives included analysing for differences between deprivation groups in pain characteristics and function that are recorded at first clinic visit.
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