In spinal cord, the mammalian target of rapamycin complex 1 (mTORC1) is implicated in chronic pain (Obara et al., 2011) but its contribution to trigeminal pain is unknown. Using immunohistochemistry, we investigated whether phospho-mTOR (p-mTOR) and phospho-S6 ribosomal protein (p-S6RP), a downstream substrate of mTORC1, are expressed in the dorsal horn (DH) of trigeminal subnucleus caudalis (Vc), a region involved in oro-facial nociception. Furthermore, changes in p-mTOR and p-S6RP expression in Vc were quantified in a Complete Freund’s Adjuvant (CFA) model of inflammatory oro-facial pain as compared to saline-injected controls. In perfusion-fixed tissue, p-mTOR and p-S6RP were co-stained with the astrocytic marker GFAP, the neuronal marker NeuN, and the microglial marker Iba1. All procedures were carried out under anaesthesia (pentobarbital, 50 mg/kg i.p.) and accorded with UK Home Office legislation. In naïve rats, p-mTOR and p-S6RP were constitutively expressed in the deep and superficial DH laminae of Vc. Following subcutaneous injection of CFA (50 µl) into the rat left whisker pad, labelling for p-mTOR was up-regulated in the ipsilateral superficial DH laminae of Vc at 24 h and 72 h post-CFA injection (p<0.001 and p<0.05, respectively) and in the deep laminae of Vc (p˂0.01) 24 h post-CFA injection. Also, at 24 h post-CFA injection p-S6RP was up-regulated in the superficial laminae of Vc in CFA-treated rats (p˂0.05). Immuno-labelling for p-mTOR showed co-localization mainly with NeuN but not GFAP or Iba1 24 h post-CFA injection. In conclusion, p-mTOR and p-S6RP are expressed in neurones of the trigeminal brainstem and are up-regulated in Vc in a model of inflammatory oro-facial pain. This suggests participation of the mTORC1 signalling pathway within the trigeminal nociceptive system and a potential contribution to chronic oro-facial pain.
Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC110
Poster Communications: Activated mammalian target of rapamycin (p-mTOR) and S6 ribosomal protein (p-S6RP) are expressed in the trigeminal subnucleus caudalis and up-regulated in a model of inflammatory oro-facial pain
W. Rothwell1, T. Iannitti1, I. Obara2, A. King1
1. School of Biomedical Sciences, University of Leeds, Leeds, United Kingdom. 2. School of Medicine, Pharmacy & Health, Durham University, Durham, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.