Contribution of peripheral versus central EP1 prostaglandin receptors to inflammatory pain

• Published in: Neuroscience letters 2011-05, Vol.495 (2), p.98-101
• Main Authors: Johansson, Torbjörn, Narumiya, Shuh, Zeilhofer, Hanns Ulrich
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Dinoprostone - pharmacology; Dorsal horn; Fundamental and applied biological sciences. Psychology; Hot Temperature; Hyperalgesia; Inflammation - metabolism; Intrathecal; Ligands; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Knockout; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; NSAIDs; Pain - metabolism; Pain - psychology; Pain relief; Pain Threshold; Peripheral Nervous System - metabolism; Peripheral Nervous System - physiopathology; Receptors, Prostaglandin E, EP1 Subtype - genetics; Receptors, Prostaglandin E, EP1 Subtype - physiology; Spinal cord; Spinal Cord - metabolism; Spinal Cord - physiopathology; Touch; Vertebrates: nervous system and sense organs; Zymosan - pharmacology
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2011.03.046

► EP1 receptors are potential targets of novel analgesic drugs. ► Their contribution to PGE 2 induced hyperalgesia was assessed in EP1 −/− mice. ► Naive EP1 −/− mice showed normal thermal and mechanical nociception. ► Heat sensitization by local peripheral PGE 2 was reduced in EP1 −/− mice. ► Sensitization by spinally injected PGE 2 was unchanged in EP1 −/− mice. Prostaglandin E 2 (PGE 2) is a key mediator of exaggerated pain sensation during inflammation. Drugs targeting the PGE 2 pathway by global inhibition of cyclooxygenases are well established in the treatment of inflammatory pain, but also cause significant unwanted effects. Enzymes downstream of the cyclooxygenases, or prostaglandin receptors are candidate targets possibly enabling therapeutic intervention with potentially fewer side effects. Among the PGE 2 receptors, the EP1 subtype has repeatedly been proposed as a promising target for treatment of inflammatory hyperalgesia. However its involvement in sensitization at specific (peripheral or central) sites has not been thoroughly investigated. Here, we have used mice deficient in the EP1 receptor (EP1 −/−) to address this issue. EP1 −/− mice showed normal mechanical and heat sensitivity during baseline conditions. Local subcutaneous PGE 2 injection into one hindpaw, caused thermal and mechanical sensitization in wild-type mice and EP1 −/− mice. Thermal sensitization in EP1 −/− mice was less than in wild-type mice while no significant difference was seen for mechanical sensitization. Injection of PGE 2 into the subarachnoid space of the lumbar spinal cord, resulted in a similar mechanical sensitization in EP1 −/− mice and in wild-type mice, while a tendency towards reduced reaction to noxious heat stimulation was observed in EP1 −/− mice. These results support a major contribution of EP1 receptors to peripheral heat sensitization, but only a minor role in mechanical sensitization and in spinal heat sensitization by PGE 2. After local subcutaneous zymosan A injection, EP1 −/− mice showed indistinguishable mechanical and heat sensitization compared with wild-type mice. Taken together, these results suggest that peripheral EP1 receptors contribute significantly to inflammation induced heat pain sensitization while evidence for a contribution to central sensitization was not obtained.