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envolvidos na modulação de outras funções, o Cejas PJ, Martínez M, Karmally S, et al. Lumbar transplant of neurons
que impede uma manipulação generalizada. A genetically modified to secrete brain-derived neurtrophic factor
terapia genética surge como um utensílio poten- attenuates allodynia and hyperalgesia after sciatic nerve constric-
tion. Pain 2000;86:195-210.
cialmente útil para contornar aqueles problemas Cobos A, Lima D, Almeida A, Tavares I. Brain afferents to the caudal: a
ao permitir efectuar uma manipulação neuroqui- retrograde and anterograde tracing study in the rat. Neurosci 2003
(no prelo).
micamente selectiva dos neurónios que partici- Chiocca EA, Breakfield XO (eds). Gene Therapy for Neurological Disor-
pam na modulação da dor. Importa estabelecer ders and Brain Tumors. New Jersey: Humana Press 1998.
detalhadamente as características dessas célu- Eaton MJ, Santiago DI, Dancausse HA, Whittemore SR. Lumbar trans-
las e os circuitos em que participam antes de plants of immortalized neurons alleviate chronic pain. Pain 1997;
72:59-69.
utilizar os vectores virais para o controlo da dor. Eaton MJ, Plunkett JA, Martínez MA, et al. Transplants of neuronal cells
Ao continuarmos a focalizar os nossos esforços bioengineered to synthetesize GABA alleviate chronic neuropathic
em duas áreas do bolbo raquidiano profunda- pain. Cell transplant 1999a;8:87-101.
mente caracterizadas pelo nosso grupo de Eaton MJ, Karmally S, Martínez MA, Plunkett JA, López T, Cejas PJ.
Lumbar transplant of neurons genetically modified to secrete gala-
investigação, acreditámos estar a dar tão so- nin reverse pain-like behaviors after after partial sciatic nerve injury.
mente um dos primeiros passos de uma longa J Peripher Nerv Syst 1999b;4:245-57.
caminhada a efectuar antes de perspectivar a Goss JR, Mata M, Goins WF, Wu HH, Glorioso JC, Fink DJ. Antinocicep-
tive effect of a genomic herpes simplex virus-based vector expres-
utilização da terapia genética para controlo da sing human proenkephalin in rat dorsal root ganglion. Gene Thera-
dor crónica. py 2001;8:551-6.
Kang W, Wilson MA, Bender MA, Glorioso JC, Wilson SP. Herpes virus-
Agradecimentos mediated preproenkephalin gene tranfert to the amydala is antino-
ciceptive. Brain research 1998;792:133-5.
A investigação incluída neste trabalho foi sub- Lima D, Almeida A. The medullary dorsal reticular nucleus as a pronoci-
ceptive centre of the pain control system. Progress in Neurobiology
sidiada pelo projecto POCTI/NSE/38952/2001 2003;66:81-108.
da Fundação para a Ciência e Tecnologia e Hao S, Mata M, Goins W, Glorioso JC, Fink DJ. Transgene-mediated
pelo “Programa Dor” da Fundação Calouste enkephalin release enhances the effect of morphine and evades
Gulbenkian. O estágio de licenciatura de Isabel tolerance to produce a sustained antiallodynic effect in neuropathic
pain. Pain 2003;102:135-42.
Martins no nosso laboratório foi patrocinada Pohl M, Braz J. Gene therapy of pain: emerging strategies and future
pelo INSERM (Institut National de la Santé et de directions. European J of Pharmac 2001;429:39-48.
la Recherche Médicale, França). Somia N, Verma IM. Gene therapy: trials and tribulations. Nature Reviews
2000;1:91-8.
Tavares I, Lima D. The caudal ventrolateral medulla as an important
Bibliografia inhibitory modulator of pain transmission in the spinal cord. J Pain
2002;3(5):337-46.
Antunes-Bras JM, Becker C, Bourgoin S, et al. Met-enkephalin is preferen- Tavares I, Albino-Teixeira A, Lima D. Perspectivas de manipulação do
tially transported into the peripheral processes of primary afferent sistema endógeno de controlo da DOR: o bolbo raquidiano ventro-
fibres in both control and HSV-1 driven proenkephalin A overex- lateral. Dor 2002;10:11-5.
pressing rats. Neurosci 2001;103:1073-83. Urban MO, Gebhart GF. Supraspinal contributions to hyperalgesia. Proc
Almeida A, Cobos A, Tavares I, Lima D. Brain afferents to the medullary Natl Acad Sci 1999;96:7687-92.
dorsal reticular nucleus: a retrograde and anterograde tracing Wilson SP, Yeomans DC, Bender MA, Lu Y, Goins WF, Glorioso JC.
study in the rat. Eur J Neurosci 2002;16(1):81-95. Antihyperalgesic effects of infection with a preproenkephalin-enco-
Braz J, Beaufour C, Coutaux A, et al. Therapeutic efficacy in experimental ding herpes virus. Proc Natl Acad Sci USA 1999;96:3211-6.
polyarthritis of viral-driven enkephalin overproduction in sensory Wilson SP, Yeomans DC. Genetic therapy for pain management. Current
neurons. J Neurosci 2001;21:7881-8. Review of Pain 2000;4:445-50.
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