Characterisation of the nociceptive phenotype of suppressible galanin overexpressing transgenic mice.
The neuropeptide galanin is widely expressed in both the central and peripheral nervous systems and is involved in many diverse biological functions. There is a substantial data set that demonstrates galanin is upregulated after injury in the DRG, spinal cord and in many brain regions where it plays a predominantly antinociceptive role in addition to being neuroprotective and pro-regenerative. To further characterise the role of galanin following nerve injury, a novel transgenic line was created using the binary transgenic tet-off system, to overexpress galanin in galaninergic tissue in a suppressible manner. The double transgenic mice express significantly more galanin in the DRG one week after sciatic nerve section (axotomy) compared to WT mice and this overexpression is suppressible upon administration of doxycycline. Phenotypic analysis revealed markedly attenuated allodynia when galanin is overexpressed and an increase in allodynia following galanin suppression. This novel transgenic line demonstrates that whether galanin expression is increased at the time of nerve injury or only after allodynia is established, the neuropeptide is able to reduce neuropathic pain behaviour. These new findings imply that administration of a galanin agonist to patients with established allodynia would be an effective treatment for neuropathic pain.
Department of Physiology and Pharmacology and Clinical Sciences at South Bristol, School of Medical Sciences, University Walk, University of Bristol, Clifton, Bristol, BS8 1TD, UK.
Robert J P
RJ
Pope
Fiona E
FE
Holmes
Niall C
NC
Kerr
David
D
Wynick
D000818:Animals; D019771:Axotomy; D004195:Disease Models, Animal; D019004:Galanin / Q000235:genetics / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009437:Neuralgia / Q000378:metabolism / Q000473:pathology; D009619:Nociceptors / Q000378:metabolism*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019004:Galanin