Premium
Role of peripheral sigma‐1 receptors in ischaemic pain: Potential interactions with ASIC and P2X receptors
Author(s) -
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.
Publication year - 2016
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.774
Subject(s) - acid sensing ion channel , receptor , pharmacology , sciatic nerve , agonist , antagonist , medicine , allodynia , nociception , ischemia , anesthesia , chemistry , ion channel , hyperalgesia
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 ( ASIC s) 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 ASIC s 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 αβme ATP . Conclusion Peripheral Sig‐1Rs contribute to the induction of ischaemia‐induced MA via facilitation of ASIC s and P2X receptors. Thus, peripheral Sig‐1Rs represent a novel therapeutic target for the treatment of ischaemic pain.