|Reference code: ||PT/FB/BL-2000-067.14|
|Location: ||Arquivo PCA - Pasta 10/2000|
|Pain control from the brain. Novel approaches of chronic pain treatment through manipulation of supraspinal areas|
|Publication year: ||2004|
The pain system is endowed with control mechanisms that modulate the ascending transmission of nociceptive input by either depressing or enhancing the responsiveness of nociceptive spinal neurons. Although effective, manipulation of brain pain-control centers as an analgesic procedure has no clinical value since it simultaneously affects neurons involved in brain functions other than pain control. In this project we explore the possibility of using viral vectors as a way of targeting specifically pain control neurons through transfection of neuronal cells that establish synaptic contacts with them. The targets chosen were the VLM and DRt because of their potent inhibitory and facilitatory effects, respectively.
The studies performed so far aimed at defining a transfection strategy that results in stimulation of the VLM and inhibition of the DRt. A replication-defective Herpes Simplex Virus was chosen since, by being retrogradely transported, it allows transfection of several brain regions projecting to the VLM and DRt, hence amplifying the effect upon each target. The migration dynamics of the virus was studied in order to identify both the brain regions that are putative sources of synaptically mediated pharmacological actions upon each target (soma exhibiting the virus product) and the regions that also receive input from the transfected neurons (axonal arborizations exhibiting the virus product). These data help in selecting the regions to be transfected from the VLM and the DRt as those that project mainly or solely to one of the two areas and do not project significantly to other brain regions. The results point to the A 5 and RVL as areas to be transfected from the VLM, and to the cerebelum, NTS, Ve and Cu as areas to be transfected from the DRt.
Complementary studies of the neurochemical nature of the transfected neurons are now in progress as a way of defining the viral construction that better conciliates the desired action upon the neurons in one target without affecting either the other target or neurons that are not involved in pain control. It was already verified that the LC contains noradrenergic neurons transfected from the VLM and DRt, and the A1
and A5 groups contain noradrenergic neurons transfected from the DRt. The surface receptor properties of VLM and DRt nociceptive neurons were evaluated in order to identify the neurotransmitters whose synthesis should be amplified or blocked by the vectors acting upon each target. GABA B receptors were found to occur in nociceptive neurons of both the VLM and DRt, and opioid receptors only in the VLM. These data point to the use of a pré-pro-enkephalin and GABAB antisense construction at the VLM and a GABA precursor construction at the DRt.
|Accessibility: ||Document does not exist in file|
|Secondary author(s): |
|Tavares, I., Almeida, A., Dugast, C., Galhardo, V., Pinto, M.|
|Document type: |
|Number of reproductions: |
|Lima, D., Tavares, I., Almeida, A., Dugast, C., Galhardo, V., & Pinto, M. (2004). Pain control from the brain. Novel approaches of chronic pain treatment through manipulation of supraspinal areas. In Aquém e além do cérebro. Behind and beyond the brain. Proceedings of the 5th Symposium of Fundação Bial (pp. 309-310). Porto: Fundação Bial.|
|Indexed document: ||No|
|Keywords: ||Psychophysiology / Pain / Viral vectors|
Pain control from the brain. Novel approaches of chronic pain treatment through manipulation of supraspinal areas