Elsevier

Neuroscience

Volume 117, Issue 1, 17 March 2003, Pages 221-227
Neuroscience

Research paper
Hyperalgesia and increased neuropathic pain-like response in mice lacking galanin receptor 1 receptors

https://doi.org/10.1016/S0306-4522(02)00779-0Get rights and content

Abstract

The neuropeptide galanin may have a role in modulation of nociception, particularly after peripheral nerve injury. The effect of galanin is mediated by at least three subtypes of receptors. In the present study, we assessed the nociceptive sensitivity in mice lacking the galanin receptor 1 gene (Galr1) and the development of neuropathic pain-like behaviours after photochemically induced partial sciatic nerve ischaemic injury. Under basal condition, Galr1 knock-out (Galr1−/−) mice had shortened response latency on the hot plate, but not tail flick and paw radiant heat, tests. The mechanical sensitivity was not different between Galr1−/− and wild type (Galr1+/+) mice, whereas the cold response was moderately enhanced in Galr1−/− mice. Both Galr1−/− mice and Galr1+/+ controls developed mechanical and heat hypersensitivity after partial sciatic nerve injury. The duration of such pain-like behaviours was significantly increased in Galr1−/−. The Galr1−/− mice and Galr1+/+ mice did not differ in their recovery from deficits in toe-spread after sciatic nerve crush.

The results provide some evidence for an inhibitory function for the neuropeptide galanin acting on galanin receptor 1 (GALR1) in nociception and neuropathic pain after peripheral nerve injury in mice.

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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