%0 Journal Article %A Andrew Moss %A Gordon Blackburn-Munro %A Emer M. Garry %A James A. Blakemore %A Tracey Dickinson %A Roberta Rosie %A Rory Mitchell %A Susan M. Fleetwood-Walker %T A Role of the Ubiquitin–Proteasome System in Neuropathic Pain %D 2002 %R 10.1523/JNEUROSCI.22-04-01363.2002 %J The Journal of Neuroscience %P 1363-1372 %V 22 %N 4 %X Neuropathic pain (characterized by hyperalgesia and allodynia to mechanical and thermal stimuli) causes cellular changes in spinal dorsal horn neurons, some of which parallel those in synaptic plasticity associated with learning. Ubiquitin C-terminal hydrolase (UCH) appears to play a key role in long-term facilitation inAplysia. The cooperation of UCH with the proteolytic enzyme complex known as the proteasome is required for the degradation of a number of signaling molecules within the cell that may remove normal restraints on synaptic plasticity. We have used electrophysiology, in situ hybridization histochemistry, semiquantitative RT-PCR, Western blotting, and in vivobehavioral reflex analysis to investigate the ubiquitin–proteasome system in a model of neuropathic pain. In neuropathic animals, ionophoretic application of selective proteasome inhibitors attenuated dorsal horn neuron firing evoked by normally innocuous brush or cold stimuli and by noxious mustard oil stimuli. In control animals, only mustard oil-evoked responses were inhibited. Intrathecal administration of proteasome inhibitors attenuated hyperalgesia and allodynia in neuropathic rats. Expression of UCH-L1 (a rat homolog ofAplysia neuronal UCH and of the human UCH-L1, also known as PGP 9.5) and its mRNA were selectively increased within the ipsilateral dorsal horn of neuropathic rats, supporting the idea of a role for the ubiquitin–proteasome system in nociceptive processing. Proteasome inhibitors selectively attenuate allodynic and hyperalgesic responses in neuropathic pain, with some reduction in normal nociceptive, but not non-nociceptive responses, and potentially represent a novel therapeutic strategy for neuropathic pain. %U https://www.jneurosci.org/content/jneuro/22/4/1363.full.pdf