Electroacupuncture Relieves Neuropathic Pain via Adenosine 3 Receptor Activation in the Spinal Cord Dorsal Horn of Mice

Int. J. Mol. Sci., 2024 · DOI: https://doi.org/10.3390/ijms251910242 · Published: September 24, 2024

Cardiovascular Science Alternative Medicine Pain Management

Simple Explanation

Neuropathic pain (NPP) is a chronic pain condition that is difficult to treat. This study explores electroacupuncture (EA) as a potential treatment for NPP by investigating the role of adenosine receptors in the central nervous system. EA treatment was found to upregulate Adora-3 and CD73 by inhibiting ADA expression in the spinal cord of mice. This process triggers the release of adenosine, which modulates pain responses and enhances neuronal activation. Using an Adora-3 agonist and antagonist, researchers showed that activating Adora-3 with an agonist increased pain thresholds, while blocking Adora-3 with an antagonist exacerbated neuropathic pain. This confirms that EA modulates NPP by regulating the Adora-3 signaling pathway.

Study Duration

Not specified

Participants

SPF male adult mice (C57BL/6 J)

Evidence Level

Level: Not specified, Study type: Animal Study

Key Findings

1
EA upregulates Adora-3 and CD73 expression while inhibiting ADA expression in the spinal cord dorsal horn (SCDH) of mice with spared nerve injury (SNI)-induced neuropathic pain.
2
Spinal adenosine levels are necessary for the anti-nociceptive effects of EA, with increased adenosine levels correlating with increased paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL).
3
Activation of the Adora-3 receptor with an agonist (IB-MECA) alleviates neuropathic pain and increases Adora-3 expression in spinal neurons, while blocking Adora-3 with an antagonist (MRS1523) reverses these effects.

Research Summary

The study investigates the efficacy of electroacupuncture (EA) in mitigating neuropathic pain (NPP) in mice by examining the role of adenosine A3 receptors (Adora-3) in the central nervous system. EA treatment modulates adenosine metabolism in the spinal cord dorsal horn (SCDH) by upregulating CD73 and Adora-3 while inhibiting ADA, leading to increased adenosine release and subsequent antinociception. The analgesic effects of EA are dependent on Adora-3 receptor activation, as demonstrated by the use of Adora-3 agonists and antagonists, which either enhance or reverse the pain-relieving effects of EA, respectively.

Practical Implications

Therapeutic Potential

EA may serve as a viable alternative to chemical therapies for neuropathic pain management.

Targeted Treatment

Adora-3 receptors can be targeted for innovative therapeutic interventions for neuropathic pain.

Clinical Translation

Further research should explore the synergistic effects of EA combined with other interventions such as pharmaceuticals or physical therapies in human subjects.

Study Limitations

1
The study is limited to mice and may not directly translate to humans.
2
The investigation focused primarily on the spinal cord, with limited exploration of supraspinal mechanisms.
3
The study acknowledges the need for measuring AMP levels post-EA to confirm the hypothesis regarding its role in the analgesic effect.

Your Feedback

Was this summary helpful?

Back to Cardiovascular Science