Role of peripheral sigma‐1 receptors in ischaemic pain: Potential interactions with ASIC and P2X receptors. (11th September 2015)

• Record Type: Journal Article
• Authors: Kwon, S.G.; Roh, D.H.; Yoon, S.Y.; Choi, S.R.; Choi, H.S.; Moon, J.Y.; Kang, S.Y.; Kim, H.W.; Han, H.J.; Beitz, A.J.; Oh, S.B.; Lee, J.H.
• Is Part Of: European journal of pain. Volume 20:Number 4(2016)
• Page Start: 594
• Page End: 606
• Publication Date: 2015-09-11
• Subjects: Pain -- Periodicals; Pain -- Treatment -- Periodicals; Pain -- Physiological aspects -- Periodicals; 616.0472
• DOI: 10.1002/ejp.774
• Languages: English
• ISSNs: 1090-3801

Abstract

Abstract: Background: The role of peripheral sigma‐1 receptors (Sig‐1Rs) in normal nociception and in pathologically induced pain conditions has not been thoroughly investigated. Since there is mounting evidence that Sig‐1Rs modulate ischaemia‐induced pathological conditions, we investigated the role of Sig‐1Rs in ischaemia‐induced mechanical allodynia (MA) and addressed their possible interaction with acid‐sensing ion channels (ASICs) and P2X receptors at the ischaemic site. Methods: We used a rodent model of hindlimb thrombus‐induced ischaemic pain (TIIP) to investigate their role. Western blot was performed to observe changes in Sig‐1R expression in peripheral nervous tissues. MA was measured after intraplantar (i.pl.) injections of antagonists for the Sig‐1, ASIC and P2X receptors in TIIP rats or agonists of each receptor in naïve rats. Results: Sig‐1R expression significantly increased in skin, sciatic nerve and dorsal root ganglia at 3 days post‐TIIP surgery. I.pl. injections of the Sig‐1R antagonist, BD‐1047 on post‐operative days 0–3 significantly attenuated the development of MA during the induction phase, but had no effect on MA when given during the maintenance phase (days 3–6 post‐surgery). BD‐1047 synergistically increased amiloride (an ASICs blocker)‐ and TNP‐ATP (a P2X antagonist)‐induced analgesic effects in TIIP rats. In naïve rats, i.pl. injection of Sig‐1R agonist PRE‐084 alone did not produce MA; but it did induce MA when co‐administered with either an acidic pH solution or a sub‐effective dose of αβmeATP. Conclusion: Peripheral Sig‐1Rs contribute to the induction of ischaemia‐induced MA via facilitation of ASICs and P2X receptors. Thus, peripheral Sig‐1Rs represent a novel therapeutic target for the treatment of ischaemic pain.