title: Injury induced activation of extracellular signal-regulated kinase (ERK) in the rat rostral ventromedial medulla (RVM) is age dependant and requires the lamina I projection pathway.
abstract: Descending controls originating in part from the rostral ventromedial medulla (RVM) regulate the excitability of dorsal horn neurons and maintain peripheral pain states. Activation of extracellular signal regulated kinase (ERK) in RVM neurons has been shown following peripheral inflammation and is involved in generating the accompanying inflammatory hyperalgesia. Here, we show that spared nerve injury (SNI), a model of neuropathic pain, results in an increase in ERK activity in RVM neurons of adult rats 3 and 8 days following surgery. We carried out two experimental procedures to demonstrate that this increase in ERK activation was related to the increased mechanical sensitivity associated with SNI. First, we showed that lesions of the lamina I/III ascending pathway from the dorsal horn attenuated both mechanical hyperalgesia and ERK activation in the RVM. Second, we performed SNI in P10 rats. At this age, SNI did not result in mechanical hypersensitivity, as previously shown, and did not activate ERK in the RVM. Finally, the percentage of pERK expressing neurones that were also serotonergic was always around 60%, independent of pain state and age, indicating an important role for serotonin in descending controls of pain states.
authors.affiliation: Department of Cell and Developmental Biology, University College London, London, UK. ucgasmg@ucl.ac.uk
authors.forename: Sandrine M
authors.initials: SM
authors.lastname: Géranton
authors.forename: Keri K
authors.initials: KK
authors.lastname: Tochiki
authors.forename: Winnie Wy
authors.initials: WW
authors.lastname: Chiu
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Stuart
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunt
mesh_terms: D000375:Aging / Q000187:drug effects / Q000473:pathology*; D000818:Animals; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007278:Injections, Spinal; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009415:Nerve Net / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009437:Neuralgia / Q000201:enzymology / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D020671:Posterior Horn Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000494:pharmacology; D054789:Ribosome Inactivating Proteins, Type 1 / Q000008:administration & dosage / Q000494:pharmacology; D000076985:Saporins; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries* / Q000473:pathology; D012701:Serotonin / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C454685:SSP-SAP fusion protein, recombinant; D012701:Serotonin; D048049:Extracellular Signal-Regulated MAP Kinases; D000076985:Saporins