title: Evidence for spinal N-methyl-D-aspartate receptor involvement in prolonged chemical nociception in the rat.
abstract: Subcutaneous injection of formalin into the hindpaw peripheral receptive field of deep dorsal horn multireceptive (convergent) nociceptive neurones was used to produce a prolonged (1 h) activation of the cells. This chemical noxious stimulus produced a first peak of firing which lasted 10 min followed by a second peak of prolonged activity which was monitored for 50 min. gamma-D-glutamylglycine (DGG), a non-selective N-methyl-D-aspartate (NMDA) and quisqualate/kainate (non-NMDA) receptor antagonist was applied intrathecally both as a pretreatment and after the formalin. A complete abolition of both peaks of the formalin response was produced by DGG pretreatment (1000 micrograms) (n = 4). This dose produced profound inhibition of the acute C-fibre evoked responses of the same cells. However, no inhibitions were produced when the antagonist was applied once the formalin response had developed (n = 4). The selective NMDA receptor antagonist 5-amino-phosphonovaleric acid (AP5) was administered intrathecally (250 and 500 micrograms) as a 40 min pretreatment and caused a small inhibition of the first peak but a marked dose-related reduction in the second prolonged phase (n =7). AP5 did not influence the C-fibre inputs onto the cells. The non-competitive NMDA receptor channel blockers, ketamine and MK801, were administered i.v. during the second phase of firing. Ketamine (1-8 mg/kg) caused a short-lasting but marked and dose-related inhibition of the neuronal responses to formalin (n = 11). MK801 (0.5-1 mg/kg) resulted in a prolonged inhibition of cell firing during the second phase of the response (n = 11).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pharmacology, University College London, U.K.
authors.forename: J E
authors.initials: JE
authors.lastname: Haley
authors.forename: A F
authors.initials: AF
authors.lastname: Sullivan
authors.forename: A H
authors.initials: AH
authors.lastname: Dickenson
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology*; D000818:Animals; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004558:Electric Stimulation; D005557:Formaldehyde; D007649:Ketamine / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*
chemical_list: D003986:Dibenzocycloheptenes; D004151:Dipeptides; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C028929:gamma-glutamylglycine; D005557:Formaldehyde; D007649:Ketamine; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate