Alamandine Injection in the Periaqueductal Gray and Rostral Ventromedial Medulla Attenuates Allodynia Induced by Sciatic Nerve Ligation in Rats
Alamandine Injection in the Periaqueductal Gray and Rostral Ventromedial Medulla Attenuates Allodynia Induced by Sciatic Nerve Ligation in Rats
Zahra Gholami,1Ali Abbasi,2Amirali Ebrahim Babaei,3Ava Soltani Hekmat,4Kazem Javanmardi,5,*
1. Student research committee, Fasa University of Medical Sciences, Fasa, Iran 2. Student research committee, Fasa University of Medical Sciences, Fasa, Iran 3. Student research committee, Fasa University of Medical Sciences, Fasa, Iran 4. Department of Physiology, Fasa University of Medical Sciences, Fasa, Iran 5. Department of Physiology, Fasa University of Medical Sciences, Fasa, Iran
Introduction: Alamandine, a peptide known to interact with Mas-related G protein-coupled receptor subtype D (MrgD), has been implicated in moderating inflammatory signals. MrgD receptors are abundantly found in pain transmission pathways, but the role of alamandine/MrgD in pain modulation has not been thoroughly explored.
Methods: This study aimed to investigate the effects of alamandine (in doses of 10, 40, and 100 pmol) in a rat model of allodynia induced by sciatic nerve ligation, with a specific focus on examining the involvement of MrgD receptors in key brain regions associated with pain modulation, namely the ventrolateral periaqueductal gray (vlPAG) and rostral ventromedial medulla (RVM).
Results: Microinjection of alamandine into the vlPAG at a dose of 100 pmol and into the RVM at doses of 40 and 100 pmol resulted in a significant increase in paw withdrawal threshold (PWT), indicative of a reduction in allodynia. The inhibitory effects of alamandine were found to be dose-dependent, with higher doses eliciting stronger analgesic responses. Additionally, co-administration of D-Pro7-Ang-(1-7) at 50 pmol, an MrgD receptor antagonist, effectively blocked the analgesic effects of alamandine, highlighting the critical involvement of MrgD receptors in mediating its effects. Immunofluorescence analysis confirmed the expression of MrgD receptors in the vlPAG and RVM regions. Notably, we observed an upregulation of MrgD receptor expression following the induction of allodynia, indicating a potential compensatory mechanism in response to pain. These findings underscore the significance of MrgD receptors in pain modulation and suggest their involvement in the action of alamandine.
Conclusion: The significant inhibitory effects of alamandine on allodynia, coupled with the presence and upregulation of MrgD receptors, highlight its promising therapeutic potential as a modulator of allodynia. Further investigations into the underlying mechanisms and signaling pathways involved in alamandine-induced analgesia and MrgD receptor function are warranted to comprehensively understand the therapeutic implications of this intriguing peptide.