title: Role of intracellular calcium in acute thermal pain perception.
abstract: The role of intracellular calcium in acute thermal nociception was investigated in the mouse hot-plate test. Intracerebroventricular (i.c.v.) administration of TMB-8, a blocker of Ca++ release from intracellular stores, produced hypernociception. By contrast, i.c.v. pretreatment with thapsigargin, a depletor of Ca++ intracellular stores, produced an increase of the mouse pain threshold. Furthermore, non-analgesic doses of thapsigargin prevented the hypernociception produced by TMB-8. In mice undergoing treatment with heparin, an InsP3-receptor antagonist, or ryanodine, a ryanodine receptor (RyR) antagonist, a dose-dependent reduction of the pain threshold was observed. Pretreatment with D-myo inositol, compound which produces InsP3, and 4-chloro-m-cresol, a RyR agonist, induced an antinociceptive effect. The heparin hypernociception was prevented by D-myo inositol, but not by L-myo inositol, used as negative control. In the same experimental conditions, the antinociception induced by D-myo inositol was prevented by a non-hyperalgesic dose of heparin. Similarly, the reduction of pain threshold produced by ryanodine was reversed by non-analgesic doses of 4-chloro-m-cresol, whereas the antinocicpetion induced by 4-chloro-m-cresol was prevented by non-hyperalgesic doses of ryanodine. The pharmacological treatments employed did not produce any behavioral impairment of mice as revealed by the rota-rod and hole-board tests. These results indicate that a variation of intracellular calcium contents at a supraspinal level is involved in the modulation of acute thermal nociception. In particular, the stimulation of both InsP3- and Ry-receptors appears to play an important role in the induction of antinociception in mice, whereas a blockade of these receptors is involved in an hypernociceptive response to acute thermal pain.
authors.affiliation: Department of Preclinical and Clinical Pharmacology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. nicoletta.galeotti@unifi.it
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Galeotti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bartolini
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
mesh_terms: D000208:Acute Disease; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000188:drug therapy; D007276:Injections, Intraventricular; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D051379:Mice; D010146:Pain / Q000523:psychology*; D017288:Pain Threshold / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D019837:Ryanodine Receptor Calcium Release Channel; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium