title: Antinociceptive effect of cyclic phosphatidic acid and its derivative on animal models of acute and chronic pain.
abstract: BACKGROUND
  Cyclic phosphatidic acid (cPA) is a structural analog of lysophosphatidic acid (LPA), but possesses different biological functions, such as the inhibition of autotaxin (ATX), an LPA-synthesizing enzyme. As LPA is a signaling molecule involved in nociception in the peripheral and central systems, cPA is expected to possess analgesic activity. We characterized the effects of cPA and 2-carba-cPA (2ccPA), a chemically stable cPA analog, on acute and chronic pain.
  
  
  RESULTS
  (1) The systemic injection of 2ccPA significantly inhibited somato-cardiac and somato-somatic C-reflexes but not the corresponding A-reflexes in anesthetized rats. (2) 2ccPA reduced sensitivity measured as the paw withdrawal response to electrical stimulation applied to the hind paws of mice through the C-fiber, but not Aδ or Aβ. (3) In mice, pretreatment with 2ccPA dose-dependently inhibited the second phase of formalin-induced licking and biting responses. (4) In mice, pretreatment and repeated post-treatments with 2ccPA significantly attenuated thermal hyperalgesia and mechanical allodynia following partial ligation of the sciatic nerve. (5) In rats, repeated post-treatments with 2ccPA also significantly attenuated thermal hyperalgesia and mechanical allodynia following chronic sciatic nerve constriction.
  
  
  CONCLUSIONS
  Our results suggest that cPA and its stable analog 2ccPA inhibit chronic and acute inflammation-induced C-fiber stimulation, and that the central effects of 2ccPA following repeated treatments attenuate neuropathic pain.
authors.affiliation: Department of Biology, Faculty of Science, Ochanomizu University, 2-1-1 Ohtsuka, Bunkyo-ku, Tokyo 112-8610, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Kakiuchi
authors.forename: Jun
authors.initials: J
authors.lastname: Nagai
authors.forename: Mari
authors.initials: M
authors.lastname: Gotoh
authors.forename: Harumi
authors.initials: H
authors.lastname: Hotta
authors.forename: Hiromu
authors.initials: H
authors.lastname: Murofushi
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Ogawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
authors.forename: Kimiko
authors.initials: K
authors.lastname: Murakami-Murofushi
mesh_terms: D000208:Acute Disease; D000758:Anesthesia; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D003498:Cyclic P-Oxides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D005557:Formaldehyde; D006930:Hyperalgesia / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008246:Lysophospholipids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009619:Nociceptors / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010146:Pain / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D010712:Phosphatidic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013696:Temperature
chemical_list: C558317:2-carba-cyclic phosphatidic acid; D003498:Cyclic P-Oxides; D008246:Lysophospholipids; D010712:Phosphatidic Acids; D005557:Formaldehyde