Additive Effects of Environmental Enrichment and Ketamine on Neuropathic Pain Relief by Reducing Glutamatergic Activation in Spinal Cord Injury in Rats

Frontiers in Neuroscience, 2021 · DOI: 10.3389/fnins.2021.635187 · Published: March 22, 2021

Spinal Cord Injury Neurology Pain Management

Simple Explanation

Spinal cord injury (SCI) often leads to chronic neuropathic pain and motor dysfunction. This study explores the combined effect of environmental enrichment (EE) and ketamine, a clinical analgesic, on SCI-induced neuropathic pain and motor dysfunction in rats. Rats with SCI were treated with either ketamine, EE, or a combination of both. Researchers then monitored pain-like behaviors, motor function, and changes in the spinal cord to understand how these treatments impact recovery. The study found that the combined treatment of EE and ketamine provided greater pain relief and locomotor recovery than either treatment alone. This improvement was associated with reduced inflammation and changes in glutamate receptor activation in the spinal cord.

Study Duration

28 days

Participants

Adult male Sprague–Dawley rats (250–300 g)

Evidence Level

Not specified

Key Findings

1
The joint treatment of EE and ketamine provided greater relief of pain-like behaviors and locomotor recovery than either paradigm alone.
2
These improvements were associated with reduced cavitation area, astrogliosis, and perilesional phosphorylation of glutamate N-methyl-D-aspartate receptor (NMDAR).
3
Lumbar spinal analysis showed reduced activation of NMDAR, mitogen-activated protein kinase (MAPK) family, nuclear factor (NF)-κB, interleukin (IL)-1β signaling, and restored excitatory amino acid transporter 2 level.

Research Summary

This study investigates the effects of combining environmental enrichment (EE) and ketamine on neuropathic pain and motor dysfunction in rats with spinal cord injury (SCI). The results demonstrate that the combined treatment is more effective than either treatment alone in alleviating pain-like behaviors and improving locomotor recovery. The underlying mechanisms involve reduced inflammation, decreased activation of glutamate receptors, and restoration of glutamatergic signaling in the spinal cord.

Practical Implications

Improved SCI Treatment Strategies

The study suggests that combining environmental enrichment and ketamine may be a more effective treatment strategy for neuropathic pain and motor dysfunction following spinal cord injury.

Multifaceted Neurorehabilitation

The findings support a multifaceted neurorehabilitation approach to improve outcomes for SCI patients.

Targeting Glutamatergic Activation

The study highlights the importance of targeting glutamatergic activation in the spinal cord to alleviate neuropathic pain and promote recovery after SCI.

Study Limitations

1
The spinal hemisection model rarely occurs in the clinic.
2
Increased hindpaw withdrawal response could result from hyperreﬂexia rather than pain after SCI.
3
Findings from this study may be replicated in other SCI models, such as contusion injury

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