Unmasking the tonic-aversive state in neuropathic pain

  • A Corrigendum to this article was published on 01 August 2010


Tonic pain has been difficult to demonstrate in animals. Because relief of pain is rewarding, analgesic agents that are not rewarding in the absence of pain should become rewarding only when there is ongoing pain. We used conditioned place preference to concomitantly determine the presence of tonic pain in rats and the efficacy of agents that relieve it. This provides a new approach for investigating tonic pain in animals and for evaluating the analgesic effects of drugs.

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Figure 1: Inhibition of spontaneous neuropathic pain and evoked hypersensitivity can be dissociated by spinally administered drugs.
Figure 2: Repeated or single trial conditioning provides negative reinforcement and unmasks spontaneous neuropathic pain.
Figure 3: Spontaneous neuropathic pain requires descending modulation.

Change history

  • 09 June 2010

    In the version of this article initially published, a citation was inadvertently omitted. To correct this, “Attempts to measure the negatively reinforcing actions of MK-801, an NMDA receptor inhibitor, on chronic pain using CPP in a rat model of inflammation have been made, but the data were not conclusive 16” has been inserted following the first sentence in the fourth paragraph. A reference was also added to the reference list as follows: 16. Sufka, K.J. Pain 58, 355–366 (1994). The error has been corrected in the HTML and PDF versions of the article.


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Author information




T.K. was partly responsible for design, data analysis, interpretation, writing and editing of the manuscript and figures. L.V.-P. was partly responsible for data collection and analysis. T.G. contributed to the SNI experiments. T.W.V., G.D. and J.L. provided conceptual input to the design and interpretation of the experiments. H.L.F. and F.P. jointly conceived and designed the studies and contributed to the interpretation, writing and editing of the manuscript.

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Correspondence to Frank Porreca.

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King, T., Vera-Portocarrero, L., Gutierrez, T. et al. Unmasking the tonic-aversive state in neuropathic pain. Nat Neurosci 12, 1364–1366 (2009). https://doi.org/10.1038/nn.2407

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