Enhancing spinal cord stimulation-induced pain inhibition by augmenting endogenous adenosine signalling after nerve injury in rats

British Journal of Anaesthesia, 2024 · DOI: 10.1016/j.bja.2024.01.005 · Published: February 2, 2024

Simple Explanation

Spinal cord stimulation (SCS) is used to treat chronic pain, but how it works isn't fully understood. This study looks at how adenosine receptors in the spinal cord affect SCS's ability to reduce pain. The study found that activating adenosine A1 and A3 receptors (A1R, A3R) in the spinal cord helps SCS inhibit pain signals. Also, using a drug (dCF) to boost adenosine levels can make SCS work even better. This suggests that combining drugs that increase adenosine with SCS could be a new way to improve pain relief for people with nerve damage.

Study Duration

Not specified

Participants

Adult male SpragueeDawley rats (6e8 weeks old)

Evidence Level

Not specified

Key Findings

1
Adora1 is highly expressed in spinal neurones, including both VGlut2-labelled excitatory neurones and Pax2-labeled inhibitory interneurones, but only in a small percentage of glial cells.
2
A1R and A3R signalling still exerted a tonic inhibition of spinal nociceptive transmission after nerve injury.
3
Intrathecal deoxycoformycin in combination with spinal cord stimulation might represent an innovative drug repurposing strategy to improve spinal cord stimulation analgesia and speed translation.

Research Summary

This study aimed to elucidate the roles of adenosine A1 and A3 receptors (A1R, A3R) in the inhibition of spinal nociceptive transmission by SCS, and further explored whether 20-deoxycoformycin (dCF), an inhibitor of adenosine deaminase, can potentiate SCS-induced analgesia. Spinal A1R and A3R signalling can exert tonic suppression and also contribute to SCS-induced inhibition of spinal nociceptive transmission after nerve injury. Inhibition of adenosine deaminase may represent a novel adjuvant pharmacotherapy to enhance SCS-induced analgesia.

Practical Implications

Improved Pain Management

Combining adenosine deaminase inhibitors with spinal cord stimulation may enhance pain relief.

Targeted Therapy

Adenosine A1 and A3 receptors are potential targets for pain control in SCS.

Drug Repurposing

Deoxycoformycin could be repurposed to improve spinal cord stimulation analgesia.

Study Limitations

1
Specificities of A1R and A3R antibodies may warrant further validation.
2
Changes in A1R and A3R expression may be different under other neuropathic pain models, females, and at different post-injury time points.
3
Relative contributions of presynaptic and postsynaptic A1R and A3R activation in spinal pain transmission and SCS-induced analgesia need to be further explored.

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