Activation of protein kinase C in the spinal cord produces mechanical hyperalgesia by activating glutamate receptors, but does not mediate chronic muscle-induced hyperalgesia

Molecular Pain, 2006 · DOI: 10.1186/1744-8069-2-13 · Published: April 3, 2006

Simple Explanation

This study investigates the role of protein kinase C (PKC) in spinal cord in mediating chronic injury-induced pain, particularly focusing on muscle insult and its relationship with glutamate receptors. The researchers hypothesized that spinal activation of PKC mediates the late phase of hyperalgesia after muscle insult and produces mechanical hyperalgesia through activation of NMDA and non-NMDA glutamate receptors. The study found that while spinal activation of PKC does produce mechanical hyperalgesia dependent on NMDA and non-NMDA receptors, it does not play a role in chronic muscle-induced mechanical hyperalgesia.

Study Duration

Not specified

Participants

123 male Sprague-Dawley rats (250–450 g)

Evidence Level

Not specified

Key Findings

1
Intrathecal injection of PDBu (phorbol 12,13 dibutyrate) decreased the mechanical withdrawal threshold bilaterally in a dose-dependent manner, indicating increased sensitivity to pain.
2
Pretreatment with the PKC inhibitor GF109023X prevented the PDBu-induced decrease in mechanical withdrawal threshold, confirming the role of PKC in this process.
3
Pretreatment with NMDA (AP5) or non-NMDA (NBQX) receptor antagonists also prevented the PDBu-induced decrease in mechanical withdrawal threshold, suggesting that PKC acts through these glutamate receptors.

Research Summary

The study investigated the role of PKC in spinal cord in mediating chronic injury-induced pain and its relationship with glutamate receptors. Activation of PKC in the spinal cord produces mechanical hyperalgesia of the paw that depends on activation of NMDA and non-NMDA receptors. Chronic muscle-induced mechanical hyperalgesia, on the other hand, does not utilize spinal PKC.

Practical Implications

Targeted Pain Treatment

Understanding the specific pathways involved in different types of pain (e.g., acute vs. chronic, cutaneous vs. muscle) can lead to more targeted and effective pain management strategies.

Drug Development

The findings suggest that PKC inhibitors might be effective for certain types of pain, specifically those mediated by NMDA and non-NMDA receptors, but not for chronic muscle pain.

Further Research

Future studies should investigate the role of PKC activation in the development of hyperalgesia and explore the mechanisms underlying the differences between cutaneous and deep somatic tissue pain.

Study Limitations

1
The study did not determine the role of PKC activation in the development of hyperalgesia; only the maintenance of hyperalgesia was investigated.
2
The effectiveness of PKC inhibitors varied, with GF109023X being more effective than chelerythrine chloride and NPC15437, possibly due to dosing limitations related to solubility.
3
The study acknowledges the limitation that the glutamate receptor antagonists used might have had analgesic effects on their own, potentially masking the effects of PDBu.

Your Feedback

Was this summary helpful?

Back to Pharmacology