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| 21KF-048 |
The role of prostaglandin E1 as a pain mediator HCN2 channel via the EP2 receptor, trigeminal ganglion neurons of mice
1. Department of Anesthesiology and Pain Medicine, Pain Center, Seoul National University Hospital, Seoul, Republic of Korea 2. Department of Anesthesiology and Pain Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea 3. Department of Physiology, College of Medicine, Hanyang University, Seoul, Republic of Korea
Background: Prostaglandin (PG) E, including PGE1 and PGE2, is a family of naturally occurring PG. Cyclooxygenase metabolizes dihomo-γ-linolenic acid and arachidonic acid to form bioactive metabolites, including PGE1 and PGE2, respectively. Although it is well known that PGE2 plays an important role in development and maintenance of hyperalgesia and allodynia, the role of PGE1 in pain is unknown.
Methods: confirmed that PGE1 evoked orofacial pain in mice, caused by hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel activation via the EP2 receptor-cAMP dependent pathway. In behavioral tests, intradermal injection of PGE1 to the whisker pads of mice induced a reduced threshold, indicating that exposure to PGE1 enhanced the excitability of HCN channel-expressing trigeminal ganglion (TG) neurons in mice by increasing their action potential frequency.
Results: The HCN channel generated inward current (Ih) was increased by 135.3 ± 4.8% at 100 nM of PGE1 in small- or medium-sized TG of mice, and the action of PGE1 on Ih showed a concentration-dependent effect, with a median effective dose (ED50) of 29.3 nM. adenylyl cyclase inhibitor (MDL12330A) and 8-bromo-cAMP inhibited the facilitation of Ih current by PGE1. The EP2 receptor antagonist AH6809 inhibited the facilitation of Ih induced by PGE1. In addition, PGE1-induced mechanical allodynia was blocked by CsCl and AH6809.
Conclusion: Indicate that PGE1 plays a role in mechanical allodynia through HCN2 channel facilitation via the EP2 receptor in nociceptive neurons, suggesting a potential therapeutic target in that PGE1 and PGE2 could be involved in pain as endogenous substances under inflammatory conditions.
Reference:
1. Emery EC, Young GT, Berrocoso EM, Chen L, McNaughton PA. HCN2 ion channels play a central role in inflammatory and neuropathic pain. Science 2011; 333: 1462-6
2. Lee DH, Chang L, Sorkin LS, Chaplan SR. Hyperpolarization-activated, cation-nonselective, cyclic nucleotide-modulated channel blockade alleviates mechanical allodynia and suppresses ectopic discharge in spinal nerve ligated rats. J Pain 2005; 6: 417-24
Methods: confirmed that PGE1 evoked orofacial pain in mice, caused by hyperpolarization-activated cyclic nucleotide-gated (HCN) 2 channel activation via the EP2 receptor-cAMP dependent pathway. In behavioral tests, intradermal injection of PGE1 to the whisker pads of mice induced a reduced threshold, indicating that exposure to PGE1 enhanced the excitability of HCN channel-expressing trigeminal ganglion (TG) neurons in mice by increasing their action potential frequency.
Results: The HCN channel generated inward current (Ih) was increased by 135.3 ± 4.8% at 100 nM of PGE1 in small- or medium-sized TG of mice, and the action of PGE1 on Ih showed a concentration-dependent effect, with a median effective dose (ED50) of 29.3 nM. adenylyl cyclase inhibitor (MDL12330A) and 8-bromo-cAMP inhibited the facilitation of Ih current by PGE1. The EP2 receptor antagonist AH6809 inhibited the facilitation of Ih induced by PGE1. In addition, PGE1-induced mechanical allodynia was blocked by CsCl and AH6809.
Conclusion: Indicate that PGE1 plays a role in mechanical allodynia through HCN2 channel facilitation via the EP2 receptor in nociceptive neurons, suggesting a potential therapeutic target in that PGE1 and PGE2 could be involved in pain as endogenous substances under inflammatory conditions.
Reference:
1. Emery EC, Young GT, Berrocoso EM, Chen L, McNaughton PA. HCN2 ion channels play a central role in inflammatory and neuropathic pain. Science 2011; 333: 1462-6
2. Lee DH, Chang L, Sorkin LS, Chaplan SR. Hyperpolarization-activated, cation-nonselective, cyclic nucleotide-modulated channel blockade alleviates mechanical allodynia and suppresses ectopic discharge in spinal nerve ligated rats. J Pain 2005; 6: 417-24
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