http___medlib.mef.hr_224__2.xml
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Bach-Rojecky, Lidija and Lacković, Zdravko (2009) Central origin of the antinociceptive action of botulinum toxin type A. Pharmacology, Biochemistry, and Behavior, 94 (2). Abstract Here we provide behavioural evidence for an axonal transport and the central origin of the antinociceptive effect of botulinum toxin type A (BTX-A). In rats we investigated the effectiveness of BTX-A on "mirror pain" induced by unilateral repeated intramuscular acidic saline injections (pH 4.0). Since experimental evidence suggest that bilateral pain induced by acidic saline is of central origin, peripheral application of BTX-A should have no effect on this type of pain. However, here we demonstrated that the unilateral subcutaneous BTX-A (5U/kg) application diminished pain on the ipsilateral, and on the contralateral side too. When injected into the proximal part of a distally cut sciatic nerve, BTX-A still reduced pain on the contralateral side. Colchicine, an axonal transport blocker, when injected into the ipsilateral sciatic nerve, prevented the effect of the peripheral BTX-A injection on both sides. Additionally, when BTX-A (1U/kg) was applied intrathecally in the lumbar cerebrospinal fluid, the bilateral hyperalgesia was also reduced. The results demonstrate the necessity of retrograde axonal transport and involvement of the central nervous system for the antinociceptive activity of BTX-A. Actions (login required) Downloads Downloads per month over past year
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Bach-Rojecky, Lidija (2006) Antinociceptivno djelovanje botulinum toksina tipa A [Antinociceptive effect of botulinum toxin type A ]. PhD thesis, Sveučilište u Zagrebu. Abstract OBJECTIVE. The hypothesis of this dissertaion is that botulinum toxin type A (BT-A) has antinociceptive effect, which might include interference with mechanisms of central sensitization. MATERIALS AND METHODS. Male Wistar rats were injected with BT-A subcutaneously, intrathecally and intraneuronally. Antinociceptive effect of BT-A was investigated in nociceptive, inflammatory and neuropathic pain. The influence of BT-A on secondary bilateral hyperalgesia was explored, too. Effect of BT-A on carrageenan-induced paw edema and capsaicin-induced extravasation of proteins coupled to Evans blue was investigated. Colchicine and transection of n. ishiadicus were used as tools to prevent the axonal transport of BT-A. Western blot and immunohistochemistry were employed in order to detect the toxin in n.ishiadicus and sensory ganglia. RESULTS. BT-A decreased inflammatory and neuropathic pain, while it did not affect nociceptive pain. It did not show antiinflammatory effect. BT-A reduced bilateral secondary hyperlgesia. Colchine prevented the effectiveness of subcutaneous BT-A, while distal transection of n.ishiadicus did not affect the influence of intraneuronal BT-A on contralateral pain. CONLUSION. BT-A reduces inflammatory pain and symptoms of neuropathic pain. Antinociceptive effect of BT-A probably involves interference with central sensitization. Abstract in Croatian UVOD. Klinička opažanja ukazuju na moguće antinociceptivno djelovanje BT-A u različitih bolnih stanja. Hipoteza ove disertacije je da botulinum toksin tip A (BT-A) ima antinociceptivno djelovanje koje uključuje procese središnje senzitizacije. MATERIJALI I METODE. Na mužjacima štakora soja Wistar, BT-A je primijenjen subkutano (s.c.) u šapu, intratekalno i intraneuronalno (u n. ishiadicus). Djelovanje je ispitivano na modelima nociceptivne, upalne i neuropatske boli, a mjerena je bolnost na pritisak, toplinu, te na injiciranje formalina. Istraživano je djelovanje BT-A na upalu, i to mjerenjem povećanja obujma i mase šapa nakon s.c. primjene karagenana, te mjerenjem ektravazacije proteina vezanih uz Evansovo modrilo nakon injiciranja kapsaicina. Pri kroničnoj mišićnoj hiperalgeziji, uzrokovanoj ponovljenim intramuskularnim injiciranjem kisele otopine 0,9 % NaCl-a, ispitivano je djelovanje BT-A na sekundarnu bilateralnu hiperalgeziju. Istraživan je utjecaj inhibicije aksonalnog transporta kolhicinom i distalnom transekcijom n. ishiadicusa na djelovanje BT-A. Western blot metoda i imunohistokemija korištene su s ciljem detekcije BT-A u n.ishiadicusu i senzornim ganglijima. REZULTATI. BT-A je smanjio upalnu i neuropatsku, dok na nonciceptivnu bol nije utjecao. BT-A nije utjecao na edem, niti na ekstravazaciju proteina pri upali. BT-A je spriječio nastanak i smanjio sekundarnu bilateralnu mehaničku hiperalgeziju. Inhibicija aksonalnog transporta kolhicinom spriječila je djelovanje s.c. primijenjenog BT-A, dok transekcija n.ishiadicusa distalno od mjesta intraneuronalnog injiciranja BT-A nije utjecala na njegovo djelovanje na kontralateralnu bol. Preliminarni rezultati imunohistokemije i Western blota ukazuju na moguću nazzočnost kratkog lanca BT-A u n. ishiadicusu i senzornim ganglijima. ZAKLJUČAK. BT-A je djelotvoran pri uklananju upalne boli i pri smanjenju simptoma neuroptske boli. Antinociceptvno djelovanje BT-A vjerojatno uključuje promjene središnje senzitizacije. Actions (login required) Downloads Downloads per month over past year