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

Nat Neurosci, 2008 · DOI: 10.1038/nn2069 · Published: April 1, 2008

Neurology Pain Management Regenerative Medicine & Stem Cells

Simple Explanation

Dorsal root injury often leads to permanent sensory loss because nerve fibers can't regrow into the spinal cord. This study found that a growth factor called artemin, when given systemically, helps these nerve fibers re-enter the spinal cord. Artemin treatment not only allowed sensory fibers to re-enter and function within the spinal cord, but also helped restore complex behaviors like grasping, and these improvements lasted for at least six months after treatment. The fact that artemin can be given systemically (throughout the body) and still promote nerve regeneration offers a significant advantage over methods requiring direct spinal injections, potentially making it easier to translate into clinical treatments.

Study Duration

6 Months

Participants

Male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Systemic artemin administration promotes the regrowth of both myelinated and unmyelinated axons through the dorsal root entry zone (DREZ).
2
Artemin treatment caused a rapid, progressive recovery of thermal and mechanical thresholds in dorsal root crush injury rats, with nocifensive responses approaching normal levels within 7 days.
3
Systemic artemin resulted in a gradual, progressive improvement in the ability of rats to walk across a ladder and a marked recovery of the stabilization maneuver.

Research Summary

Systemic artemin treatment caused the regeneration of damaged axons, resulting in virtually complete and long-lasting restoration of nociceptive and sensorimotor functions. Artemin, given in six systemic injections over 11 d promoted the regeneration of multiple classes of nerve fibers through the DREZ, re-established the functional spinal synaptic connections, and restored nociceptive functions, sensorimotor functions and complex, directed sensorimotor behavior. Notably, artemin was administered systemically and promoted substantial functional recovery even after a 2-d delay in administration, suggesting that it has substantial and possibly permanent potential therapeutic application.

Practical Implications

Potential Therapy for Nerve Injuries

Systemic artemin could offer a new approach to treating traumatic nerve injuries, promoting axonal regeneration and functional recovery.

Advantage Over Spinal Injections

The systemic administration of artemin provides a less invasive alternative to spinal injections, potentially reducing associated risks and improving clinical applicability.

Window of Opportunity for Treatment

The effectiveness of artemin even with a delayed administration suggests a therapeutic window for treating dorsal root injuries after trauma.

Study Limitations

1
A possible contribution of sprouting of uninjured fibers in the dorsal horn and perhaps cuneate nucleus to the observed functional recovery cannot be excluded.
2
Although sprouting of these uninjured fibers may contribute to the restoration of function, retrograde labeling of sensory neurons from the spinal dorsal horn shows that artemin strongly promotes regeneration of injured axons.
3
Non-GFRα3 mechanisms may also be possible, and these possibilities require further investigation.

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