From neuroanatomy to gene therapy: searching for new ways to manipulate the supraspinal endogenous pain modulatory system

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Isaura Tavares (Author) FMUP; Deolinda Lima (Author) FMUP

Journal

Title: Journal of Anatomy

Vol. 211

Pages: 261-268

ISSN: 0021-8782

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 35 Citations

Scopus - 33 Citations

Other information

Authenticus ID: P-004-8FR

DOI: 10.1111/j.1469-7580.2007.00759.x

Abstract (EN): The enclogenous pain modulatory system is a complex network of brain areas that control nociceptive transmission at the spinal cord by inhibitory and facilitatory actions. The balance between these actions ensures effective modulation of acute pain, while during chronic pain the pronociceptive effects appear to prevail. The mechanisms underlying this imbalance were studied as to the role of two medullary components of the pain modulatory system: the dorsal reticular nucleus and the caudal ventrolateral medulla, which function primarily as pronociceptive and antinociceptive centres, respectively. Both areas are connected with the spinal dorsal horn by closed reciprocal loops. In the spino-clorsal reticular nucleus loop, the ascending branch is strongly inhibited by spinal GABAergic neurons, which may act as a buffering system of the dorsal reticular nucleus-centred amplifying effect. In the spino-caudal ventrolateral medulla loop, the ascending branch is under potent excitation of substance P (SP) released from primary afferents, which is likely to trigger the intense descending inhibition detected in acute pain. During chronic pain, the activity in the lateral reticular formation of the caudal ventrolateral medulla changes, so that the action of the caudal ventrolateral medulla upon SP-responsive spinal neurons shifts from inhibitory to excitatory. The mechanisms of this modulatory shift are unknown but probably relate to the decresed expression of p-opioid, delta-opioid and GABA(B) receptors. Normalizing receptor expression in the caudal ventrolateral medulla or controlling noci-evoked activity at the dorsal reticular nucleus or caudal ventrolateral medulla by interfering with neurotransmitter release is now possible by the use of gene therapy, an approach that stands out as a unique tool to manipulate the supraspinal enclogenous pain control system.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8