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Interaction of endokinin A/B and (Mpa(6))-γ2-MSH-6-12 in pain regulation in mice
Lanxia Zhou1, Qing Yang2, Chunbo He2
1The Core Laboratory of the First Affiliated Hospital, Lanzhou University, 1 Donggang West Road, Lanzhou 730000, China; Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou 730000, China.
Abstract:
The present study focused on the interactive effects of (Mpa(6))-γ2-MSH-6-12 (Mpa, spinal level) and endokinin A/B (EKA/B, supraspinal level) on pain regulation in mice. EKA/B (30 pmol) only weakened 100 pmol Mpa-induced hyperalgesia at 5 min, but could enhance it during 20-30 min. However, EKA/B (100 pmol) antagonized all dose levels of Mpa significantly at 5 min and blocked them completely at 10 min. EKA/B (3 nmol) co-injected with Mpa presented marked analgesia at 5 min and enduring hyperalgesia within 20-60 min. To investigate the underlying mechanisms between Mpa and EKA/B, SR140333B and SR142801 (NK1 and NK3 receptor antagonists, respectively) were utilized. SR140333B had no influence on Mpa, while SR142801 potentiated it during 20-30 min. Whereas, SR140333B and SR142801 could block the co-administration of Mpa and EKA/B (30 pmol) separately at 5 min and 30 min. These phenomena might attribute to that these two antagonists promoted the antagonism of EKA/B (30 pmol) at the early stage, while antagonized EKA/B preferentially in the latter period. SR140333B weakened the analgesia of EKA/B (3 nmol), but produced no effect on Mpa. However, SR140333B failed to affect the co-injection of Mpa and EKA/B, which implied that EKA/B cooperated with Mpa prior to SR140333B. These results could potentially help to better understand the interaction of NK and MrgC receptors in pain regulation in mice.
Insights
This study reveals complex interactions between spinal Mpa(6)-γ2-MSH-6-12 and supraspinal endokinin A/B in mouse pain regulation. Their combined effects depend on dosage and timing, influencing pain perception through distinct receptor pathways.
Area of Science:
- Neuroscience
- Pharmacology
- Pain Research
Background:
- Pain regulation involves complex interactions between spinal and supraspinal pathways.
- The roles of Mpa(6)-γ2-MSH-6-12 (Mpa) at the spinal level and endokinin A/B (EKA/B) at the supraspinal level in pain are not fully understood.
- Investigating these interactions can elucidate novel mechanisms for pain management.
Purpose of the Study:
- To investigate the interactive effects of Mpa and EKA/B on pain regulation in mice.
- To explore the underlying receptor mechanisms involved in the Mpa-EKA/B interaction.
- To determine how NK1 and NK3 receptor antagonists influence these interactions.
Main Methods:
- Administration of Mpa and EKA/B at varying doses and time points in mice.
- Co-administration of Mpa with different doses of EKA/B.
- Utilizing NK1 receptor antagonist (SR140333B) and NK3 receptor antagonist (SR142801) to probe mechanisms.
- Assessing hyperalgesia and analgesia following drug administration.
Main Results:
- EKA/B's effect on Mpa-induced hyperalgesia varied with dose and time, showing both weakening and enhancement.
- Higher doses of EKA/B antagonized Mpa-induced hyperalgesia, while lower doses showed complex temporal effects.
- SR142801 potentiated Mpa effects, while SR140333B did not, suggesting differential receptor involvement.
- Both antagonists could block the co-administration effects of Mpa and EKA/B, indicating complex interplay.
Conclusions:
- The interaction between spinal Mpa and supraspinal EKA/B in pain modulation is dose- and time-dependent.
- NK1 and NK3 receptors play distinct roles in mediating these interactions.
- These findings provide insights into the complex interplay of MrgC and NK receptors in pain pathways.
- Understanding these interactions may lead to novel therapeutic strategies for pain management.
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