title: Intracellular messengers involved in spontaneous pain, heat hyperalgesia, and mechanical allodynia induced by intrathecal dihydroxyphenylglycine.
abstract: We investigated the role of two intracellular second messengers, extracellular signal-regulated protein kinase (ERK) and protein kinase C (PKC), in a model of persistent pain using intrathecal (i.t.) (R,S)-3,5-dihydroxyphenylglycine (DHPG). Spontaneous nociceptive behaviours (SNBs), mechanical allodynia (von Frey thresholds) and heat hyperalgesia (plantar test latencies) induced by DHPG were measured in animals pretreated i.t. with membrane permeable inhibitors of ERK (PD 98059) and PKC (GF 109203X). Spinal administration of PD 98059 dose-dependently reduced SNBs, and attenuated both mechanical allodynia and heat hyperalgesia induced by DHPG. GF 109203X treatment also reduced SNBs and heat hyperalgesia, but did not affect mechanical allodynia induced by DHPG. Neither PD 98059, nor GF 109203X, altered mechanical or thermal thresholds in saline-injected control rats. These results suggest that both ERK and PKC are involved in persistent pain associated with the i.t. administration of DHPG.
authors.affiliation: Department of Anesthesia, McGill University, Canada; Department of Psychology, McGill University, Canada.
authors.forename: Snijezanna S
authors.initials: SS
authors.lastname: Ambrosini
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Coderre
mesh_terms: D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006358:Hot Temperature / Q000009:adverse effects*; D006930:Hyperalgesia / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D006941:Hyperesthesia / Q000139:chemically induced / Q000378:metabolism*; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D012118:Resorcinols / Q000008:administration & dosage; D014110:Touch
chemical_list: D012118:Resorcinols; C079215:3,5-dihydroxyphenylglycine; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D005998:Glycine