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Bach-Rojecky, Lidija and Šalković-Petrišić, Melita and Lacković, Zdravko (2010) Botulinum toxin type A reduces pain supersensitivity in experimental diabetic neuropathy: Bilateral effect after unilateral injection. European Journal of Pharmacology, [Epub . Abstract We investigated antinociceptive activity of botulinum toxin type A (BTX-A) in a model of diabetic neuropathic pain in rats. Male Wistar rats were made diabetic by a single intraperitoneal injection of streptozotocin (80mg/kg). Sensitivity to mechanical and thermal stimuli was measured with the paw-pressure and hot-plate test, respectively. The formalin test was used to measure sensitivity to chemical stimuli. Diabetic animals with pain thresholds lower for at least 25% compared to the non-diabetic group were considered neuropathic and were injected with BTX-A either subcutaneously (3, 5 and 7U/kg) or intrathecally (1U/kg). Mechanical and thermal sensitivity was measured at several time-points. After peripheral application, BTX-A (5 and 7U/kg) reduced mechanical and thermal hypersensitivity not only on ipsilateral, but on contralateral side, too. The antinociceptive effect started 5days following BTX-A injection and lasted at least 15days. Formalin-induced hypersensitivity in diabetic animals was abolished as well. When applied intrathecally, BTX-A (1U/kg) reduced diabetic hyperalgesia within 24h supporting the assumption of retrograde axonal transport of BTX-A from the peripheral site of injection to central nervous system. The results presented here demonstrate the long-lasting pain reduction after single BTX-A injection in the animals with diabetic neuropathy. The bilateral pain reduction after unilateral toxin application and the effectiveness of lower dose with the faster onset after the intrathecal injection suggest the involvement of the central nervous system in the antinociceptive action of BTX-A in painful diabetic neuropathy. 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