Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat

Background Earlier studies show that endogenous sphingolipids can induce pain hypersensitivity, activation of spinal astrocytes, release of proinflammatory cytokines and activation of TRPM3 channel. Here we studied whether the development of pain hypersensitivity induced by sphingolipids in the spinal cord can be prevented by pharmacological inhibition of potential downstream mechanisms that we hypothesized to include TRPM3, sigma(1) and NMDA receptors, gap junctions and D-amino acid oxidase. Methods Experiments were performed in adult male rats with a chronic intrathecal catheter for spinal drug administrations. Mechanical nociception was assessed with monofilaments and heat nociception with radiant heat. N,N-dimethylsphingosine (DMS) was administered to induce pain hypersensitivity. Ononetin, isosakuranetin, naringenin (TRPM3 antagonists), BD-1047 (sigma(1) receptor antagonist), carbenoxolone (a gap junction decoupler), MK-801 (NMDA receptor antagonist) and AS-057278 (inhibitor of D-amino acid oxidase, DAAO) were used to prevent the DMS-induced hypersensitivity, and pregnenolone sulphate (TRPM3 agonist) to recapitulate hypersensitivity. Results DMS alone produced within 15 min a dose-related mechanical hypersensitivity that lasted at least 24 h, without effect on heat nociception. Preemptive treatments with ononetin, isosakuranetin, naringenin, BD-1047, carbenoxolone, MK-801 or AS-057278 attenuated the development of the DMS-induced hypersensitivity, but had no effects when administered alone. Pregnenolone sulphate (TRPM3 agonist) alone induced a dose-related mechanical hypersensitivity that was prevented by ononetin, isosakuranetin and naringenin. Conclusions Among spinal pronociceptive mechanisms activated by DMS are TRPM3, gap junction coupling, the sigma(1) and NMDA receptors, and DAAO.Peer reviewe

TRPA1 antagonists for pain relief

Peer reviewe

Accelerometer-Based Method for Extracting Respiratory and Cardiac Gating Information for Dual Gating during Nuclear Medicine Imaging

Both respiratory and cardiac motions reduce the quality and consistency of medical imaging specifically in nuclear medicine imaging. Motion artifacts can be eliminated by gating the image acquisition based on the respiratory phase and cardiac contractions throughout the medical imaging procedure. Electrocardiography (ECG), 3-axis accelerometer, and respiration belt data were processed and analyzed from ten healthy volunteers. Seismocardiography (SCG) is a noninvasive accelerometer-based method that measures accelerations caused by respiration and myocardial movements. This study was conducted to investigate the feasibility of the accelerometer-based method in dual gating technique. The SCG provides accelerometer-derived respiratory (ADR) data and accurate information about quiescent phases within the cardiac cycle. The correct information about the status of ventricles and atria helps us to create an improved estimate for quiescent phases within a cardiac cycle. The correlation of ADR signals with the reference respiration belt was investigated using Pearson correlation. High linear correlation was observed between accelerometer-based measurement and reference measurement methods (ECG and Respiration belt). Above all, due to the simplicity of the proposed method, the technique has high potential to be applied in dual gating in clinical cardiac positron emission tomography (PET) to obtain motion-free images in the future.</p

Amygdaloid administration of tetrapentylammonium attenuates development of pain and anxiety-like behavior following peripheral nerve injury

Background: The central amygdaloid nucleus (CeA) is involved in processing and descending regulation of pain. Amygdaloid mechanisms underlying pain processing and control are poorly known. Here we tested the hypothesis that perioperative CeA administration of tetrapentylammonium (TPA), a non-selective THIK-1 channel blocker and thereby inhibitor of microglia, attenuates development of chronic neuropathic pain and comorbid anxiety-like behavior. Methods: Rats with a spared nerve injury (SNI) model of neuropathy or sham operation had a chronic cannula for drug microinjections into the CeA or a control injection site. Monofilament test was used to evaluate pain, and light-dark box (LDB) to assess anxiety. Results: Perioperative CeA treatment with TPA (30 mu g/day up to the third postoperative day, D3) significantly attenuated the development of pain and anxiety-like behavior. In the late phase (> D14), CeA administration of TPA (3-30 mu g) failed to influence pain. Perioperative minocycline (microglia inhibitor; 25 mu g), MK-801 (an N-Methyl-D-aspartate receptor antagonist; 0.1 mu g), vehicle or TPA in a control injection site failed to attenuate pain development. Conclusions: Perioperative treatment of the CeA with TPA delayed development of neuropathic pain and comorbid anxiety-like behavior, while TPA treatment failed to influence maintenance of established neuropathic pain. The failures to attenuate pain development with CeA administrations of minocycline or MK-801 do not support the hypothesis that the TPA-induced prophylactic effect was due to inhibition of amygdaloid microglia or N-methyl-D-aspartate receptors. While TPA in the CeA proved to have a prophylactic effect on SNI-induced pain behavior, the underlying mechanism still remains to be studied. (c) 2018 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.Peer reviewe

Spinal TRPA1 Contributes to the Mechanical Hypersensitivity Effect Induced by Netrin-1

Netrin-1, a chemoattractant expressed by floor plate cells, and one of its receptors (deleted in colorectal cancer) has been associated with pronociceptive actions in a number of pain conditions. Here, we addressed the question of whether spinal TRPC4/C5 or TRPA1 are among the downstream receptors contributing to pronociceptive actions induced by netrin-1. The experiments were performed on rats using a chronic intrathecal catheter for administration of netrin-1 and antagonists of TRPC4/C5 or TRPA1. Pain sensitivity was assessed behaviorally by using mechanical and heat stimuli. Effect on the discharge rate of rostral ventromedial medullary (RVM) pain control neurons was studied in lightly anesthetized animals. Netrin-1, in a dose-related fashion, induced mechanical hypersensitivity that lasted up to three weeks. Netrin-1 had no effect on heat nociception. Mechanical hypersensitivity induced by netrin-1 was attenuated by TRPA1 antagonist Chembridge-5861528 and by the control analgesic compound pregabalin both during the early (first two days) and late (third week) phase of hypersensitivity. TRPC4/C5 antagonist ML-204 had a weak antihypersensitivity effect that was only in the early phase, whereas TRPC4/C5 antagonist HC-070 had no effect on hypersensitivity induced by netrin-1. The discharge rate in pronociceptive ON-like RVM neurons was increased by netrin-1 during the late but not acute phase, whereas netrin-1 had no effect on the discharge rate of antinociceptive RVM OFF-like neurons. The results suggest that spinal TRPA1 receptors and pronociceptive RVM ON-like neurons are involved in the maintenance of submodality-selective pronociceptive actions induced by netrin-1 in the spinal cord

Spinal TRPA1 Contributes to the Mechanical Hypersensitivity Effect Induced by Netrin-1

Netrin-1, a chemoattractant expressed by floor plate cells, and one of its receptors (deleted in colorectal cancer) has been associated with pronociceptive actions in a number of pain conditions. Here, we addressed the question of whether spinal TRPC4/C5 or TRPA1 are among the downstream receptors contributing to pronociceptive actions induced by netrin-1. The experiments were performed on rats using a chronic intrathecal catheter for administration of netrin-1 and antagonists of TRPC4/C5 or TRPA1. Pain sensitivity was assessed behaviorally by using mechanical and heat stimuli. Effect on the discharge rate of rostral ventromedial medullary (RVM) pain control neurons was studied in lightly anesthetized animals. Netrin-1, in a dose-related fashion, induced mechanical hypersensitivity that lasted up to three weeks. Netrin-1 had no effect on heat nociception. Mechanical hypersensitivity induced by netrin-1 was attenuated by TRPA1 antagonist Chembridge-5861528 and by the control analgesic compound pregabalin both during the early (first two days) and late (third week) phase of hypersensitivity. TRPC4/C5 antagonist ML-204 had a weak antihypersensitivity effect that was only in the early phase, whereas TRPC4/C5 antagonist HC-070 had no effect on hypersensitivity induced by netrin-1. The discharge rate in pronociceptive ON-like RVM neurons was increased by netrin-1 during the late but not acute phase, whereas netrin-1 had no effect on the discharge rate of antinociceptive RVM OFF-like neurons. The results suggest that spinal TRPA1 receptors and pronociceptive RVM ON-like neurons are involved in the maintenance of submodality-selective pronociceptive actions induced by netrin-1 in the spinal cord.Peer reviewe

Valkoposkihanhi pääkaupunkiseudulla

Valkoposkihanhesta on tullut vajaassa parissa kymmenessä vuodessa pääkaupunkiseudun nurmikoita ja rantoja näkyvästi hallitseva laji. Ilmiö ei ole irrallaan samanlaisesta kehityksestä koko Itämeren piirissä. Valkoposkihanhi on asettunut jäädäkseen alueen linnustoon. Tämän julkaisun tarkoitus on koota yhteen Helsingin yliopiston metsäekologian laitoksen tekemän ja ohjaaman valkoposkihanhen seurannan tulokset ja kokemukset erilaisista menetelmistä niiden aiheuttamien haittojen torjunnassa. Tarkoitus on ollut hakea lintudirektiivin tarkoittamaa muuta tyydyttävää ratkaisua sen sijaan, että ongelmia ratkaistaisiin poikkeamalla valkoposkihanhea koskevista rauhoitussäännöksistä. Ennaltaehkäisyn keinoja tulisikin ottaa käyttöön ja kehittää niitä edelleen