Increased fronto-hippocampal connectivity in the Prrxl1 knockout mouse model of congenital hypoalgesia

• Type: Article in International Scientific Journal
• Date: 2016

Authors

Clara Monteiro (Author) FMUP; Helder Cardoso-Cruz (Author) FMUP; Matos, M (Author) Other; Dourado, M (Author) Other; Lima, D (Author) Other; Vasco Galhardo (Author) FMUP

Journal

Title: Pain

Vol. 157

Pages: 2045-2056

ISSN: 0304-3959

Publisher: Wolters Kluwer Health

Indexing

ISI Web of Knowledge - 8 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-00K-TZX

DOI: 10.1097/j.pain.0000000000000611

Abstract (EN): Despite the large number of studies addressing how prolonged painful stimulation affects brain functioning, there are only a handful of studies aimed at uncovering if persistent conditions of reduced pain perception would also result in brain plasticity. Permanent hypoalgesia induced by neonatal injection of capsaicin or carrageenan has already been shown to affect learning and memory and to induce alterations in brain gene expression. In this study, we used the Prrxl1(-/-) model of congenital mild hypoalgesia to conduct a detailed study of the neurophysiological and behavioral consequences of reduced pain experience. Prrxl1 knockout animals are characterized by selective depletion of small diameter primary afferents and abnormal development of the superficial dorsal laminae of the spinal cord, resulting in diminished pain perception but normal tactile and motor behaviour. Behavioral testing of Prrxl1(-/-) mice revealed that these animals have reduced anxiety levels, enhanced memory performance, and improved fear extinction. Neurophysiological recordings from awake behaving Prrxl1(-/-) mice show enhanced altered fronto-hippocampal connectivity in the theta-and gamma-bands. Importantly, although inflammatory pain by Complete Freund Adjuvant injection caused a decrease in fronto-hippocampal connectivity in the wild-type animals, Prrxl1(-/-) mice maintained the baseline levels. The onset of inflammatory pain also reverted the differences in forebrain expression of stress-and monoamine-related genes in Prrxl1(-/-) mice. Altogether our results suggest that congenital hypoalgesia may have an effect on brain plasticity that is the inverse of what is usually observed in animal models of chronic pain.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12