Sidos 2013 : Katsaus kansainvälisen liiketoiminnan ja kulttuurin toimialan työelämäläheisyyteen

Sidos 2013 esittelee Kymenlaakson ammattikorkeakoulun kansainvälisen liiketoiminnan ja kulttuurin toimialan työelämäyhteistyötä. Sidos on työelämälähtöinen julkaisu, jossa tiiviiden artikkeleiden avulla tehdään tunnetuksi konkreettisia tapauksia ammattikorkeakoulun opetuksen, tutkimuksen ja työelämän välisestä vuorovaikutuksesta. Julkaisu on suunnattu ammattikorkeakoulun yhteistyökumppaneille, omalle henkilökunnalle, opiskelijoille sekä kaikille, jotka ovat kiinnostuneita siitä arvokkaasta työstä, jota toimialoillamme tehdään alueen työ- ja elinkeinoelämän kanssa

Uusien kipulääkkeiden kehitys on haastavaa

Uudella mekanismilla vaikuttavien kipulääkkeiden kehitys on haastavaa. Käymme läpi joitakin onnistuneita ja pitkälle edenneitä kehitysprojekteja sekä hieman historiaa

Neurophysiological response properties of medullary pain-control neurons following chronic treatment with morphine or oxycodone : modulation by acute ketamine

Descending facilitatory circuitry that involves the rostroventromedial medulla (RVM) exerts a significant role in the development of antinociceptive tolerance and hyperalgesia following chronic morphine treatment. The role of the RVM in the development of antinociceptive tolerance to oxycodone, another clinically used strong opioid. is not yet known. Ketamine, an N-methyl-o-aspartate (NMDA) receptor antagonist, attenuates opioid antinociceptive tolerance, but its effect on RVM cell discharge in opioid-tolerant animals is not known. Here, we compared chronic effects of morphine and oxycodone on the discharge properties of RVM cells and attempted to attenuate chronic treatment-induced changes with ketamine. Parallel recordings of RVM cell discharge and limb withdrawal response were performed under light pentobarbital anesthesia in male rats following sustained systemic treatment with morphine or oxycodone at equianalgesic doses. Ongoing activity and the response to noxious heat and pinch were determined in pronociceptive RVM ON-cells and antinociceptive OFF-cells on the sixth treatment day. Proportions of RVM cell types were not changed. Chronic oxycodone induced antinociceptive tolerance both in limb withdrawal and RVM cell activity. Chronic morphine induced antinociceptive tolerance in limb withdrawal that was accompanied by pronociceptive heat response changes in RVM ON- and OFF-cells. A behaviorally subantinociceptive dose of acute ketamine reversed antinociceptive tolerance both to morphine and oxycodone in limb withdrawal and reversed the chronic morphine-induced pronociceptive discharge changes in RVM cells. The results indicate that an NMDA receptor-dependent descending pronociceptive circuitry involving the RVM has an important role in behavioral antinociceptive tolerance to morphine but not oxycodone. NEW & NOTEWORTHY Morphine and oxycodone are two clinically used strong opioids. Chronic treatment with oxycodone as well as morphine can lead to analgesic tolerance and paradoxical hyperalgesia. Here we show that an N-methyl-n-aspartate receptor-dependent pronociceptive change in discharge properties of rostroventromedial medullary neurons controlling spinal nociception has an important role in antinociceptive tolerance to morphine but not oxycodone. Interestingly, chronic oxycodone did not induce pronociceptive changes in the rostroventromedial medulla.Peer reviewe

Morphine-3-glucuronide causes antinociceptive cross-tolerance to morphine and increases spinal substance P expression

Morphine-3-glucuronide (M3G), the main metabolite of morphine, has been implicated in the development of tolerance and of opioid-induced hyperalgesia, both limiting the analgesic use of morphine. We evaluated the acute and chronic effects of M3G and morphine as well as development of antinociceptive cross-tolerance between morphine and M3G after intrathecal administration and assessed the expression of pain-associated neurotransmitter substance P in the spinal cord. Sprague-Dawley rats received intrathecal M3G or morphine twice daily for 6 days. Nociception and tactile allodynia were measured with von Frey filaments after acute and chronic treatments. Substance P levels in the dorsal horn of the spinal cord were determined by immunohistochemistry after 4-day treatments. Acute morphine caused antinociception as expected, whereas acute M3G caused tactile allodynia, as did both chronic M3G and morphine. Chronic M3G also induced antinociceptive cross-tolerance to morphine. M3G and morphine increased substance P levels similarly in the nociceptive laminae of the spinal cord. This study shows that chronic intrathecal M3G sensitises animals to mechanical stimulation and elevates substance P levels in the nociceptive laminae of the spinal cord. Chronic M3G also induces antinociceptive cross-tolerance to morphine. Thus, chronic M3G exposure might contribute to morphine-induced tolerance and opioid-induced hyperalgesia.Peer reviewe

Antagonism of peripheral opioid receptors by methylnaltrexone does not prevent morphine tolerance in rats

Opioids are effective analgesics in the management of severe pain. However, tolerance, leading to dose escalation and adverse effects are significant limiting factors in their use. The role of peripheral opioid receptors in analgesia has been discussed especially under inflammatory conditions. The results from pharmacological and conditional knockout studies together do not provide a clear picture of the contribution of peripheral opioid receptors on antinociceptive tolerance and this needs to be evaluated. Therefore, we studied whether the peripherally restricted opioid receptor antagonist, methylnaltrexone (MNTX), could prevent morphine tolerance without attenuating the antinociceptive effect of morphine. Male Sprague-Dawley rats were treated for 7 days with increasing subcutaneous doses of morphine (5-30 mg/kg) and were coadministered saline, MNTX (0.5 or 2 mg/kg), or naltrexone (NTX; 2 mg/kg). Nociception was assessed with tail-flick, hotplate, and von Frey tests. Morphine, MNTX, and NTX concentrations in the plasma, brain, and spinal cord were measured by liquid chromatography-tandem mass spectrometry. In acute coadministration, NTX, but not MNTX, abolished the acute antinociceptive effects of morphine in all nociceptive tests. The antinociceptive tolerance after repeated morphine administration was also prevented by NTX but not by MNTX. MNTX penetrated to the spinal cord and the brain to some extent after repeated administration. The results do not support the use of MNTX for preventing opioid tolerance and also suggest that morphine tolerance is mediated by central rather than peripheral opioid receptors in the rat.Peer reviewe

Kielletyt aineet ja menetelmät urheilussa ja erivapaus urheilijan lääkityksessä

Dopingvalvonnan alaiset kilpaurheilijat sairastavat ja voivat tarvita hoitoa lääkkeillä tai menetelmillä, jot‑ ka ovat kiellettyjen aineiden ja menetelmien luettelossa. Urheilussa kielletyt lääkeaineet voi tarkistaa Suomessa myyntiluvallisten valmisteiden osalta ”Kielletyt aineet ja menetelmät urheilussa” (KAMU) ‑lää‑ kehaun avulla. Mikäli tasomäärittelyn piiriin kuuluvan urheilijan sairauden hoito vaatii jonkin kielletyn lääkeaineen käyttöä, hoidolle voidaan hakea erivapautta. Erivapauden hakuohjeistukseen löytyy linkki KAMUsta ja SUEKin sivuilta (1). Dopingvalvonta on tehostunut analyysi- ja testausmenetelmien kehit‑ tyessä. Tehokas antidopingtoiminta vähentää urheilussa kiellettyjen aineiden väärinkäyttöä ja niiden ai‑ heuttamia terveyshaittoja sekä tukee puhtaiden urheilijoiden tasavertaista kilpailua.</p

Kielletyt aineet ja menetelmät urheilussa ja erivapaus urheilijan lääkityksessä

Vertaisarvioitu.Dopingvalvonnan alaiset kilpaurheilijat sairastavat ja voivat tarvita hoitoa lääkkeillä tai menetelmillä, jotka ovat kiellettyjen aineiden ja menetelmien luettelossa. Urheilussa kielletyt lääkeaineet voi tarkistaa Suomessa myyntiluvallisten valmisteiden osalta "Kielletyt aineet ja menetelmät urheilussa" (KAMU) -lääkehaun avulla. Mikäli tasomäärittelyn piiriin kuuluvan urheilijan sairauden hoito vaatii jonkin kielletyn lääkeaineen käyttöä, hoidolle voidaan hakea erivapautta. Erivapauden hakuohjeistukseen löytyy linkki KAMUsta ja SUEKin sivuilta (1). Dopingvalvonta on tehostunut analyysi- ja testausmenetelmien kehittyessä. Tehokas antidopingtoiminta vähentää urheilussa kiellettyjen aineiden väärinkäyttöä ja niiden aiheuttamia terveyshaittoja sekä tukee puhtaiden urheilijoiden tasavertaista kilpailua.Peer reviewe

Novel RET agonist for the treatment of experimental neuropathies

The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) alleviate symptoms of experimental neuropathy, protect and stimulate regeneration of sensory neurons in animal models of neuropathic pain, and restore their functional activity. However, clinical development of GFL proteins is complicated by their poor pharmacokinetic properties and multiple effects mediated by several receptors. Previously, we have identified a small molecule that selectively activates the major signal transduction unit of the GFL receptor complex, receptor tyrosine kinase RET, as an alternative to GFLs, for the treatment of neuropathic pain. We then introduced a series of chemical changes to improve the biological activity of these compounds and tested an optimized compound named BT44 in a panel of biological assays. BT44 efficiently and selectively stimulated the GFL receptor RET and activated the intracellular mitogene-activated protein kinase/extracellular signal-regulated kinase pathway in immortalized cells. In cultured sensory neurons, BT44 stimulated neurite outgrowth with an efficacy comparable to that of GFLs. BT44 alleviated mechanical hypersensitivity in surgery- and diabetes-induced rat models of neuropathic pain. In addition, BT44 normalized, to a certain degree, the expression of nociception-related neuronal markers which were altered by spinal nerve ligation, the neuropathy model used in this study. Our results suggest that the GFL mimetic BT44 is a promising new lead for the development of novel disease-modifying agents for the treatment of neuropathy and neuropathic pain.Peer reviewe