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DocumentPain control from the brain. Novel approaches of chronic pain treatment through manipulation of supraspinal areas2004

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2000
Location: Arquivo PCA - Pastas 1 a 13/2000
Title:
2000 Grants
Start date: 2001-01 - 2014-02
Dimension/support:
13 caixas de arquivo

Reference code: PT/FB/BL-2000-067
Location: Arquivo PCA - Pasta 10/2000
Title:
067 - Pain control from the brain. Novel approaches of chronic pain treatment through manipulation of supraspinal areas
Duration: 2000-12 - 2003-12
Researcher(s):
Deolinda Lima, Isaura Ferreira Tavares, Armando Alberto da Nova Pinto de Almeida, Christophe Dugast, Vasco Miguel Clara Lopes Galhardo, Marta Sofia Carvalho Teixeira Pinto
Institution(s): Instituto de Histologia e Embriologia da Faculdade de Medicina do Porto (Portugal)
Contents: Contents:
Application form
Correspondence
Financial report and expenditure documents
Progress reports
Final report
1 Article
Language: eng
Author:
Lima, D.
Secondary author(s):
Tavares, I., Almeida, A., Dugast, C., Galhardo, V., Pinto, M.
Number of reproductions:
1
Keywords:
Psychophysiology / Pain

Reference code: PT/FB/BL-2000-067.14
Location: Arquivo PCA - Pasta 10/2000
Title:
Pain control from the brain. Novel approaches of chronic pain treatment through manipulation of supraspinal areas
Publication year: 2004
URL:
http://www.bial.com/pt/fundacao_bial.11/simposios.19/edicoes_anteriores.75/5%C2%BA_simposio.a111.html
Abstract/Results: ABSTRACT:
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
Language:
eng
Author:
Lima, D.
Secondary author(s):
Tavares, I., Almeida, A., Dugast, C., Galhardo, V., Pinto, M.
Document type:
Conference abstract
Number of reproductions:
1
Reference:
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

Pain control from the brain. Novel approaches of chronic pain treatment through manipulation of supraspinal areas
DocumentPain control from the brain: Gene therapy in the treatment of chronic pain2010

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2004
Location: Arquivo PCA - Pastas 1 a 25/2004
Title:
2004 Grants
Start date: 2005-01 - 2012-09
Dimension/support:
25 caixas de arquivo

Reference code: PT/FB/BL-2004-015
Location: Arquivo PCA - Pasta 21/2004
Title:
015 - Pain control from the brain - Gene therapy in the treatment of chronic pain
Duration: 2005-01 - 2009-01
Researcher(s):
Deolinda Lima, Isaura Ferreira Tavares, Marta Pinto, Isabel Martins
Institution(s): Instituto de Histologia e Embriologia, Faculdade de Medicina da Universidade do Porto (Portugal)
Contents: Contents:
Bursary agreement
Application form
Correspondence
Financial report and expenditure documents
Progress reports
Final report
3 posters
Language: eng
Author:
Lima, D.
Secondary author(s):
Tavares, I., Pinto, M., Martins, I.
Number of reproductions:
1
Keywords:
Psychophysiology / Pain

Reference code: PT/FB/BL-2004-015.14
Location: Arquivo PCA - Pasta 21/2004
Title:
Pain control from the brain: Gene therapy in the treatment of chronic pain
Publication year: 2010
URL:
http://www.bial.com/simposio/Livro_de_Actas_8_Simposio.pdf
Abstract/Results: ABSTRACT:
OBJECTIVES: Develop new methods of manipulation of the supraspinal pain control system to correct the neurobiological changes induced by chronic pain. The studies were focused on two components of the supraspinal pain control system: the dorsal reticular nucleus (DRt) and the caudal ventrolateral medulla(VLM). These two areas were elected based on the profound knowledge of their participation in pain modulation at the spinal cord level. The DRt is involved in pain facilitation whereas the VLM appears to be involved in mixed effects (facilitatory and inhibitory).
METHODS:
Transduction of neurons by HSV-1 (Herpes-Simplex Virus, type 1) or lentiviral based constructs (replication- defective forms) and evaluation of nociceptive behaviours in sustained and chronic pain models. In the case of the DRt, three studies were performed using the following constructs and pain models: 1) HSV-1 vectors
overexpressing pre-proenkephalin in monoarthritic animals; 2) HSV-1 vectors overexpressing mu-opioid receptors (MOR) in a neuropathic pain model; 3) HSV-1 vectors that reduce the release of noradrenaline in a neuropathic pain model. In the VLM, we studied the effect of overexpressing pre-proenkephalin in an inflammatory pain model.
RESULTS:
In summary, the studies demonstrated that chronic pain affects descending modulation and that gene transfer can correct those effects in a sustained manner. The studies indicate that during chronic pain, a depression in the expression of MOR at the DRt is associated with hyperalgesic effects induced by local injection of opioids. The hyeperalgesia induced by overexpression of enkephalins at the DRt can be switched to analgesia by overexpression of MOR. It is possible that the VLM does not undergo similar changes since local overexpression of enkephalins induces analgesia. A decrease of noradrenaline release at the DRt is analgesic probably because chronic pain increases the tonus of noradrenergic input to the DRt and facilitates pain modulation from this nucleus.
CONCLUSION:
By allowing sustained and directed manipulation, gene transfer is an effective tool to study pain modulation from the brain. Vector constructs produced taking into account the specific changes induced by chronic pain in the brain will continue to be developed.
PUBLICATIONS (full papers):
1. Pinto M, Lima D, Tavares I. (2007). Neuronal activation at the spinal cord and medullary pain control centres after brief stimulation of an inflamed joint: a c-fos study in the monoarthritic rat. Neuroscience, 147:1076-1089.
2. Pinto M, Castro AR, Tushdy F, Wilson SP, Lima D, Tavares I. (2008). Opioids modulate pain facilitation from the dorsal reticular nucleus. Mol. Cell Neurosci, 39: 508-518.
3. Pinto M, Sousa M, Lima D, Tavares I. (2008) Expression of µ-opioid, GABAB and NK1 receptors in spinally-projecting neurons of the caudal medulla oblongata: implications for descending modulation of nociceptive transmission. J. Comp. Neurol., 510: 175-187.
4. Tavares I, Lima D. (2007). From neuroanatomy to gene therapy: searching for new ways to manipulate the supraspinal endogenous pain modulatory system. J. Anatomy, 211: 261-268.
5. Martins I, Pinto M, Lima D, Wilson SP, Tavares I. (2008). Dynamic of migration of HSV-1 from a medullary pronociceptive centre: antinociception by overexpression of the preproenkephalin transgene". Eur. J. Neurosci., 28: 2075-2083.
Accessibility: Document does not exist in file
Language:
eng
Author:
Lima, D.
Secondary author(s):
Tavares, I., Pinto, M., Martins, I.
Document type:
Conference abstract
Number of reproductions:
1
Reference:
Lima, D., Tavares, I., Pinto, M., & Martins, I. (2010). Pain control from the brain: Gene therapy in the treatment of chronic pain. In Aquém e além do cérebro. Behind and beyond the brain. Proceedings of the 8th Symposium of Fundação Bial (pp. 184-185). Porto: Fundação Bial.
Indexed document: No
Keywords: Receptor expression / Animal models / Gene transfer / Viral vectors

Pain control from the brain: Gene therapy in the treatment of chronic pain

Pain control from the brain: Gene therapy in the treatment of chronic pain
DocumentOpioids modulate pain facilitation from the dorsal reticular nucleus2008

Reference code: PT/FB
Entity holding: BIAL Foundation
Location: S. Mamede do Coronado
Title:
BIAL Foundation Archive
Start date: 1994
History:
The BIAL Foundation was created in 1994 by Laboratórios BIAL in conjunction with the Council of Rectors of Portuguese Universities. BIAL’s Foundation mission is to foster the scientific study of Man from both the physical and spiritual perspectives.
Along the years the BIAL Foundation has developed an important relationship with the scientific community, first in Portugal and after worldwide. Today it is an institution of reference which aims to stimulate new researches that may help people, promote more health and contribute to new milestones to gain access to knowledge.
Among its activities the BIAL Foundation manages the BIAL Award, created in 1984, one of the most important awards in the Health field in Europe. The BIAL Award rewards both the basic and the clinical research distinguishing works of major impact in medical research.
The BIAL Foundation also assigns Scientific Research Scholarships for the study of neurophysiological and mental health in people, arousing the interest of researchers in the areas of Psychophysiology and Parapsychology.
To date the BIAL Foundation has supported 461 projects, more than 1000 researchers, with research groups in twenty-seven countries, resulting, until April 2013, in about 600 full papers, out of which 172 published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Since 1996 the BIAL Foundation organizes the Symposia entitled "Behind and Beyond the Brain", a Forum that gathers well renowned neurosciences speakers and the BIAL Foundation Fellows which are spread around the world.
Classified as an institution of public utility, the BIAL Foundation includes among its patrons the Portuguese President, the Portuguese Universities Rectors' Council and the Portuguese Medical Association.
URL: http://www.bial.com/pt/
Accessibility: By permission

Reference code: PT/FB/BL
Entity holding: BIAL Foundation
Title: BIAL Grants
Start date: 1994
History:
In 1994 the BIAL Foundation launched a programme of science research grants with the aim of encouraging the research into Man’s physical and mental processes, namely in fields still largely unexplored but which warrant further scientific analysis, as Psychophysiology and Parapsychology.
Since its launch, applications to the BIAL grants have been increasing. Up to now 461 projects have been supported, involving more than 1000 researchers from 27 countries.
The approved applications have benefited from grants in amounts comprised between €5,000 and €50, 000. The amount to be granted is fixed by the Scientific board according to the needs of each project.
The supported projects have originated, until April 2013, in about 600 full papers, 172 out of which were published in indexed international journals with an average impact factor of 3.6 and a substantial number of citations (1665).
Among the BIAL Foundation fellows is worth highlighting the presence of scientists from prestigious universities from the United States, United Kingdom, Australia, Russia, Germany, Japan, France, Canada, and many others.
The BIAL grants are promoted biannually.

Reference code: PT/FB/BL-2004
Location: Arquivo PCA - Pastas 1 a 25/2004
Title:
2004 Grants
Start date: 2005-01 - 2012-09
Dimension/support:
25 caixas de arquivo

Reference code: PT/FB/BL-2004-015
Location: Arquivo PCA - Pasta 21/2004
Title:
015 - Pain control from the brain - Gene therapy in the treatment of chronic pain
Duration: 2005-01 - 2009-01
Researcher(s):
Deolinda Lima, Isaura Ferreira Tavares, Marta Pinto, Isabel Martins
Institution(s): Instituto de Histologia e Embriologia, Faculdade de Medicina da Universidade do Porto (Portugal)
Contents: Contents:
Bursary agreement
Application form
Correspondence
Financial report and expenditure documents
Progress reports
Final report
3 posters
Language: eng
Author:
Lima, D.
Secondary author(s):
Tavares, I., Pinto, M., Martins, I.
Number of reproductions:
1
Keywords:
Psychophysiology / Pain

Reference code: PT/FB/BL-2004-015.15
Location: Arquivo PCA - Pasta 21/2004
Title:
Opioids modulate pain facilitation from the dorsal reticular nucleus
Publication year: 2008
URL:
http://www.sciencedirect.com/science/article/pii/S1044743108001863
Abstract/Results: ABSTRACT:
During chronic pain, the supraspinal pain modulatory system undergoes plastic changes with enhancement of facilitation transmission at the spinal cord. The changes induced by chronic pain at descending modulation often affect opioidergic modulation, and were never described for a key facilitatory component of the system, the dorsal reticular nucleus (DRt). Neurochemical characterization of the DRt-spinal pathway showed that d-opioid receptors are positioned as to indirectly modulate the activity of non-projecting DRt neurons, whereas neurons expressing µ-opioid receptors project to the spinal dorsal horn or act as interneurons, the latter of which co-expressing GABAB receptors. In monoarthritic rats, the expression of µ-opioid receptors decreased in the DRt whereas the levels of endogenous enkephalin remained unaltered. To increase the opioidergic inhibition of the DRt, we locally injected selective agonists of d- and µ-opioid receptors or a viral vector containing the human preproenkephalin transgene. Injection of the Herpes Simplex viral vector encoding preproenkephalin induced thermal hypoalgesia in non-inflamed animals and hyperalgesia in monoarthritic rats. The opioid agonists [D-Ala2, Glu4]-deltorphin (DELT) and [D-Ala2, NMePhe4Gly-ol5]-enkephalin (DAMGO) induced thermal hyperalgesia in both non-inflamed and monoarthritic rats, but with lower doses in the latter group. The present study shows that opioidergic neurons at the DRt are modulated by GABAergic cells herein controlling the descending facilitation of pain transmission. The DRt exhibits plastic changes during chronic inflammatory pain, with decrease opioid receptor expression which may account for increased descending facilitation during chronic pain.
Accessibility: Document does not exist in file
Language:
eng
Author:
Pinto, M.
Secondary author(s):
Castro, A. R., Tushdy, F., Wilson, S. P., Lima, D., Tavares, I.
Document type:
Article
Number of reproductions:
1
Reference:
Pinto, M., Castro, A. R., Tushdy, F., Wilson, S. P., Lima, D., & Tavares, I. (2008). Opioids modulate pain facilitation from the dorsal reticular nucleus. Molecular and Cellular Neuroscience, 39(4), 508-518. doi: 10.1016/j.mcn.2008.07.008
2-year Impact Factor: 3.934|2008
Times cited: 26|2022-05-19
Indexed document: Yes
Quartile: Q1
Keywords: Psychophysiology / Chronic pain / Viral vectors