Sensory neuronal phenotype in galanin receptor 2 knockout mice: focus on dorsal root ganglion neurone development and pain behaviour.
Galanin is a 29-amino-acid peptide expressed in dorsal root ganglion (DRG) neurones and spinal dorsal horn neurones. It affects pain threshold and has developmental and trophic effects. Galanin acts at three G-protein-coupled receptors, galanin receptors (GalR1-3), each expressed in the DRGs as suggested by in situ hybridization and/or reverse transcriptase-polymerase chain reaction. The GalR2 knockout (-/-) mice permit studies on the contributions of this receptor subtype to the role of galanin at the spinal level. At 1 week after sciatic nerve transection (axotomy), there were 16-20% fewer neurones in intact and contralateral DRGs of -/- mice as compared with wild-type (WT) mice. In addition, a significant neurone loss (26% reduction) was found in the ipsilateral DRGs of WT mice, whereas no further neurone loss was seen in -/- mice. Expression of several peptides has been examined after axotomy, including galanin, neuropeptide Y and two of its receptors as well as substance P, and no significant differences were found between -/- and WT mice in either ipsi- or contralateral DRGs, respectively. After thermal injury and spinal nerve ligation, onset and duration of hyperalgesia in the injured paw were similar in GalR2-/- and WT animals. Recovery from spinal nerve ligation-caused allodynia had the same kinetics in -/- and WT animals. These data are in line with earlier observations from the peripheral and central nervous system, suggesting that galanin actions mediated by GalR2 subtype are of importance in neurodevelopment and neuroprotection.
Department of Neuroscience, Karolinska Institutet, S171 77 Stockholm, Sweden. Tiejun.Shi@ki.se
Tie-Jun Sten
TJ
Shi
Xiao-Ying
XY
Hua
Xiaoying
X
Lu
Shelle
S
Malkmus
Jeff
J
Kinney
Kristina
K
Holmberg
Sebastian
S
Wirz
Sandra
S
Ceccatelli
Tony
T
Yaksh
Tamas
T
Bartfai
Tomas
T
Hökfelt
D000367:Age Factors; D000818:Animals; D019771:Axotomy / Q000379:methods; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000235:genetics; D007839:Functional Laterality / Q000502:physiology; D019004:Galanin / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D017288:Pain Threshold / Q000502:physiology*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D044092:Receptor, Galanin, Type 2 / Q000172:deficiency*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D020426:Sciatic Neuropathy / Q000378:metabolism; D013124:Spinal Injuries / Q000378:metabolism; D013997:Time Factors
D012333:RNA, Messenger; D044092:Receptor, Galanin, Type 2; D019004:Galanin