Proceedings of The Physiological Society
Cardiff University (2009) Proc Physiol Soc 17, PC12
The peripheral pro- and anti-nociceptive effects of galanin are mediated by activation of GalR2
R. Hulse1, D. Wynick1, L. Donaldson1
1. Department of Physiology & Pharmacology, University of Bristol, Bristol, United Kingdom.
The neuropeptide galanin is widely expressed in the central and peripheral nervous systems and has been shown to modulate nociception, with both pro- and anti-nociceptive effects described in a dose-dependent manner (Wiesenfeld-Hallin et al. 1988, 1989). These responses were primarily studied using various spinal cord behavioural and electrophysiological paradigms. In contrast very little work has been done on the peripheral nociceptive roles played by galanin. There are currently three known galanin receptors. GalR1 and GalR2 are both expressed by subsets of sensory neurons in the dorsal root ganglia (Kerekes et al. 2003). The aim of this project was to use a saphenous nerve preparation to study the responses of mechano-sensitive primary afferents to galanin and the GalR2/3 specific agonist Gal2-11. Extracellular teased fibre recordings were made from the saphenous nerve in deeply anaesthetised naïve rats (250-350g; sodium pentobarbital, induction ~60mg/kg i.p. and maintenance ~20mg.kg-1hr-1 i.v.). Individual nociceptive afferents were identified and characterised (conduction velocity <1m/s, mechanical threshold >1g, not brush sensitive). Nociceptive afferents were classified as galanin “responders” if mechanical responses were affected by close arterial injection of 0.1mM galanin. Intra-arterial 0.1mM Gal2-11 both increased activity evoked by 26g. mechanical stimulation (n=14, evoked firing rate before Gal2-11 1.82Hz +0.66 vs after Gal2-11 2.69Hz + 0.85 p<0.05) and decreased mechanical activation thresholds (n=14, before Gal2-11 18.0g +33.0 vs after Gal2-11 4.0g + 8.0 (median+IQR), p<0.05), in a manner similar to the effect of galanin (Hulse et al. 2008). In galanin-responsive nociceptors, low concentrations of (100nM) Gal2-11 administered subcutaneously adjacent to the receptive fields caused a similar effect to Gal2-11 administered intra-arterially, in that mechanically evoked activity was enhanced and mechanical activation thresholds decreased (n=4, before 20.5g +15.5 vs after 2.7g + 3.8, *p<0.05) in these nociceptors (i.e. a pronociceptive change). In further experiments, subcutaneous injection of high concentration (10µM) Gal2-11 caused an increase in mechanical activation thresholds (i.e. an anti-nociceptive change) in nociceptive afferents (n=5, before 26.0g + 36.0 vs after Gal2-11 100.0g + 154.00, p<0.05). This study demonstrates that activation of GalR2 in peripheral cutaneous afferent terminals exerts both pro- and anti-nociceptive effects on mechanonociceptors, in a dose-dependent manner.
Where applicable, experiments conform with Society ethical requirements