title: The effects of peptide and lipid endocannabinoids on arthritic pain at the spinal level.
abstract: BACKGROUND
  Hemopressin, a nonapeptide (PVNFKFLSH: HP) derived from the α chain of hemoglobin was shown to interact specifically with brain cannabinoid CB(1) receptors. Therefore, it seems to be the only peptide structure with cannabinoid activities. Our goal in this study was to further characterize this peptide and to clarify the antinociceptive potency of the polyunsaturated fatty acid derivates, 2-arachidonoyl-glycerol (2-AG) and anandamide, by investigating their effects on mechanical allodynia at the spinal level.
  
  
  METHODS
  HP was prepared on solid phase by in situ neutralization. After chronic intrathecal catheterization, mechanical hypersensitivity was produced in male Wistar rats by injection of carrageenan (300 μg/30 μL) into the tibiotarsal joint of one of the hind legs. Three hours after carrageenan administration, the ligands were administered intrathecally. The mechanical threshold was assessed using a dynamic aesthesiometer.
  
  
  RESULTS
  2-AG (1-200 μg) and anandamide (10-200 μg) decreased carrageenan-induced mechanical allodynia in a dose-dependent manner, whereas HP had no antinociceptive effect in a wide dose range (0.3-30 μg). The effect of 2-AG was prevented by the CB(1) receptor antagonist AM 251, but not by the CB(2) antagonist SSR144528-2. HP (3 and 30 μg) also inhibited the effect of 2-AG. None of the ligands influenced the degree of edema.
  
  
  CONCLUSIONS
  HP posttreatment had no effect on mechanical allodynia, whereas spinally injected 2-AG and anandamide were potent drugs.
authors.affiliation: Department of Physiology, Faculty of Medicine, University of Szeged, Szeged, Hungary.
authors.forename: Zita
authors.initials: Z
authors.lastname: Petrovszki
authors.forename: Gyula
authors.initials: G
authors.lastname: Kovacs
authors.forename: Csaba
authors.initials: C
authors.lastname: Tömböly
authors.forename: György
authors.initials: G
authors.lastname: Benedek
authors.forename: Gyongyi
authors.initials: G
authors.lastname: Horvath
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001095:Arachidonic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D018771:Arthralgia / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control*; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control*; D063385:Cannabinoid Receptor Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D002351:Carrageenan; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000503:physiopathology / Q000517:prevention & control; D063388:Endocannabinoids; D005989:Glycerides / Q000008:administration & dosage / Q000494:pharmacology*; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D006614:Hindlimb; D007278:Injections, Spinal; D007596:Joints / Q000187:drug effects* / Q000294:innervation / Q000503:physiopathology; D008297:Male; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects; D013997:Time Factors
chemical_list: D000700:Analgesics; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; C469526:Cnr2 protein, rat; D063388:Endocannabinoids; D005989:Glycerides; D006454:Hemoglobins; D010446:Peptide Fragments; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; C473218:hemopressin; C094503:glyceryl 2-arachidonate; D002351:Carrageenan; C078814:anandamide