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Persistent restoration of sensory function by immediate or delayed systemic artemin after dorsal root injury

Nature Neuroscience volume 11, pages 488–496 (2008)Cite this article

Abstract

Dorsal root injury results in substantial and often irreversible loss of sensory functions as a result of the limited regenerative capacity of sensory axons and the inhibitory barriers that prevent both axonal entry into and regeneration in the spinal cord. Here, we describe previously unknown effects of the growth factor artemin after crush injury of the dorsal spinal nerve roots in rats. Artemin not only promoted re-entry of multiple classes of sensory fibers into the spinal cord and re-establishment of synaptic function and simple behavior, but it also, surprisingly, promoted the recovery of complex behavior. These effects occurred after a 2-week schedule of intermittent, systemic administration of artemin and persisted for at least 6 months following treatment, suggesting a substantial translational advantage. Systemic artemin administration produced essentially complete and persistent restoration of nociceptive and sensorimotor functions, and could represent a promising therapy that may effectively promote sensory neuronal regeneration and functional recovery after injury.

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Figure 1: Systemic artemin administration promotes axonal growth across the DREZ into the spinal cord.
Figure 2: Systemic artemin administration restores nociceptive responses.
Figure 3: Quantification in the ipsilateral dorsal horn of formalin-induced Fos expression and evoked NK1-R internalization after carrageenan-induced inflammation.
Figure 4: Systemic artemin administration restores synaptic responses from sensory afferent fibers in spinal neurons.
Figure 5: Systemic artemin administration promotes recovery of sensorimotor function.
Figure 6: Systemic artemin administration increases CTB labeling in cuneate nucleus at 6 months.
Figure 7: Systemic artemin administration increases retrodgrade labeling of DRG neurons from the dorsal horn.
Figure 8: Systemic artemin normalizes expression of GFRα3 and RET.

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Acknowledgements

This work was supported by grants from Biogen Idec.

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Author notes

  1. Dinah W Y Sah

    Present address: Present address: Alnylam Pharmaceuticals, 300 Third Street, 3rd floor, Cambridge, Massachusetts 02142, USA.,

Authors and Affiliations

  1. Department of Pharmacology, University of Arizona, College of Medicine, 1501 N Campbell Avenue, Tucson, 85724-5050, Arizona, USA

    Ruizhong Wang, Tamara King, Michael H Ossipov, Todd W Vanderah & Frank Porreca

  2. Biogen Idec, 14 Cambridge Center, Cambridge, 02142, Massachusetts, USA

    Anthony J Rossomando & Dinah W Y Sah

  3. Department of Physiology, Tufts University, School of Medicine, 145 Harrison Avenue, Boston, 02111, Massachusetts, USA

    Pamela Harvey, Peter Cariani & Eric Frank

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Correspondence to Frank Porreca.

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Wang, R., King, T., Ossipov, M. et al. Persistent restoration of sensory function by immediate or delayed systemic artemin after dorsal root injury. Nat Neurosci 11, 488–496 (2008). https://doi.org/10.1038/nn2069

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