Research paperHyperalgesia and increased neuropathic pain-like response in mice lacking galanin receptor 1 receptors
Section snippets
Animals
The Galr1−/− mice were generated by transfer of a genetically manipulated 129Sv embryonic stem cell carrying one mutant allele of the gene encoding GALR1 (Galr1) into C57BL/6J blastocysts, and mating of the resultant chimaeric mice with C57BL/6J mice to produce heterozygous (Galr1+/−) mice that carried the Galr1 knock-out (Galr1−/−) allele in their germ line. The heterozygous progeny of this first mating were backcrossed to C57BL/6J mice to generate Galr1+/− for mating to produce Galr1−/− and
Expression of mRNA for galanin and galanin receptors in the spinal cord
RT-PCR amplification of mRNA extracted from spinal cord confirmed the absence of normal full-length transcript encoding GALR1 in Galr1−/− mice (Fig. 1). No major differences were evident in expression of galanin and GALR2 mRNA. The possible up-regulation of GALR3 mRNA expression in Galr1−/− tissue (Fig. 1) requires confirmation with more sensitive assays, as detection of GALR3 mRNA expression was at the limits of detection for this assay.
General behaviours and baseline sensitivity
The Galr1−/− mice were normal as compared with the
Discussion
A moderately enhanced response on the hot plate test and to cold stimulation was found in Galr1−/− mice compared with Galr1+/+ mice. This supports the notion that galanin through activation of GALR1 produces antinociception in rodents (Xu et al. 2000). GALR1 is known to be coupled to inhibitory Gi/Go proteins and activation of this receptor decreases neuronal activity and/or neurotransmitter release through a number of mechanisms (Branchek et al., 2000). We have shown previously that the spinal
Acknowledgements
This study was supported by the Swedish MRC (07913, 12168), AstraZeneca, Clinical Research Center at Huddinge University Hospital and research fund of the Karolinska Institutet. KHB is supported by the Swedish Foundation for Strategic Research.
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