Differential roles of galanin on mechanical and cooling responses at the primary afferent nociceptorReportar como inadecuado

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Molecular Pain

, 8:41

First Online: 06 June 2012Received: 21 January 2012Accepted: 06 June 2012


BackgroundGalanin is expressed in a small percentage of intact small diameter sensory neurons of the dorsal root ganglia and in the afferent terminals of the superficial lamina of the dorsal horn of the spinal cord. The neuropeptide modulates nociception demonstrating dose-dependent pro- and anti-nociceptive actions in the naïve animal. Galanin also plays an important role in chronic pain, with the anti-nociceptive actions enhanced in rodent neuropathic pain models. In this study we compared the role played by galanin and its receptors in mechanical and cold allodynia by identifying individual rat C-fibre nociceptors and characterising their responses to mechanical or acetone stimulation.

ResultsMechanically evoked responses in C-fibre nociceptors from naive rats were sensitised after close intra-arterial infusion of galanin or Gal2-11 a galanin receptor-2-3 agonist confirming previous data that galanin modulates nociception via activation of GalR2. In contrast, the same dose and route of administration of galanin, but not Gal2-11, inhibited acetone and menthol cooling evoked responses, demonstrating that this inhibitory mechanism is not mediated by activation of GalR2. We then used the partial saphenous nerve ligation injury model of neuropathic pain PSNI and the complete Freund’s adjuvant model of inflammation in the rat and demonstrated that close intra-arterial infusion of galanin, but not Gal2-11, reduced cooling evoked nociceptor activity and cooling allodynia in both paradigms, whilst galanin and Gal2-11 both decreased mechanical activation thresholds. A previously described transgenic mouse line which inducibly over-expresses galanin Gal-OE after nerve injury was then used to investigate whether manipulating the levels of endogenous galanin also modulates cooling evoked nociceptive behaviours after PSNI. Acetone withdrawal behaviours in naive mice showed no differences between Gal-OE and wildtype WT mice. 7-days after PSNI Gal-OE mice demonstrated a significant reduction in the duration of acetone-induced nociceptive behaviours compared to WT mice.

ConclusionsThese data identify a novel galaninergic mechanism that inhibits cooling evoked neuronal activity and nociceptive behaviours via a putative GalR1 mode of action that would also be consistent with a TRP channel-dependent mechanism.

KeywordsGalanin Primary afferent Cold Neuropathic pain Inflammatory pain AbbreviationsCFAComplete Freunds adjuvant

c.i.aClose intra arterial

DRGDorsal root ganglia


GalRGalanin receptor

Gal-OEGalanin over-expressing transgenic mice



PSNIPartial saphenous nerve injury

WTWild-type mice.

Electronic supplementary materialThe online version of this article doi:10.1186-1744-8069-8-41 contains supplementary material, which is available to authorized users.

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Autor: Richard P Hulse - Lucy F Donaldson - David Wynick

Fuente: https://link.springer.com/

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