Transgenic overexpression of galanin in the dorsal root ganglia modulates pain-related behavior.
The neuropeptide galanin is expressed in the dorsal root ganglia (DRG) and spinal cord and is thought to be involved in the modulation of pain processing. However, its mechanisms of action are complex and poorly understood, as both facilitatory and inhibitory effects have been described. To understand further the role played by galanin in nociception, we have generated two transgenic lines that overexpress galanin in specific populations of primary afferent DRG neurons in either an inducible or constitutive manner. In the first line, a previously defined enhancer region from the galanin locus was used to target galanin to the DRG (Gal-OE). Transgene expression recapitulates the spatial endogenous galanin distribution pattern in DRG neurons and markedly overexpresses the peptide in the DRG after nerve injury but not in the uninjured state. In the second line, an enhancer region of the c-Ret gene was used to constitutively and ectopically target galanin overexpression to the DRG (Ret-OE). The expression of this second transgene does not alter significantly after nerve injury. Here, we report that intact Ret-OE, but not Gal-OE, animals have significantly elevated mechanical and thermal thresholds. After nerve damage, using a spared nerve-injury model, mechanical allodynia is attenuated markedly in both the Gal-OE and Ret-OE mice compared with WT controls. These results support an inhibitory role for galanin in the modulation of nociception both in intact animals and in neuropathic pain states.
Holmes
Fiona E
FE
University Research Centre for Neuroendocrinology, University of Bristol, Marlborough Street, United Kingdom.
Bacon
Andrea
A
Pope
Robert J P
RJ
Vanderplank
Penny A
PA
Kerr
Niall C H
NC
Sukumaran
Madhu
M
Pachnis
Vassilis
V
Wynick
David
D
D000818:Animals; D019004:Galanin / Q000235:genetics* / Q000502:physiology*; D005727:Ganglia, Spinal / Q000293:injuries / Q000502:physiology* / Q000503:physiopathology; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D010146:Pain / Q000503:physiopathology / Q000517:prevention & control*; D017288:Pain Threshold / Q000502:physiology*; D013997:Time Factors
D019004:Galanin