title: Molecular and electrophysiological changes in the prefrontal cortex-amygdala-dorsal periaqueductal grey pathway during persistent pain state and fear-conditioned analgesia.
abstract: Fear-conditioned analgesia (FCA) is the reduction in pain responding which is expressed upon re-exposure to a context previously paired with an aversive stimulus. Projections along the prefrontal cortex (PFC)-amygdala-dorsal periaqueductal grey (dPAG) pathway may mediate FCA. However, there is a paucity of studies measuring both molecular and electrophysiological changes in this pathway in rats expressing persistent pain-related behaviour or FCA. Male Lister-hooded rats, with stimulating and recording electrodes implanted in the amygdala and dPAG, respectively, either received or did not receive footshock (0.4 mA) paired with context, followed 23.5 h later by an intraplantar injection of saline or formalin (50 μL, 2.5%) into the right hindpaw. Thirty minutes post-formalin/saline, rats were re-exposed to the context for 15 min, during which pain-related behaviours were assessed in addition to evoked field potential recordings in the amygdala-dPAG pathway. Immediately after the 15-minute trial, PFC tissue was isolated for measurement of total and phosphorylated extracellular-signal regulated kinase (ERK) by western blotting. Formalin-evoked nociceptive behaviour in non-fear-conditioned rats was associated with increased field potential amplitude in the dPAG and increased relative expression of phospho-ERK in the PFC. These effects were abolished in rats expressing FCA. Fear conditioning in non-formalin treated rats was associated with increased phospho-ERK in the PFC but no change in field potential amplitude in the dPAG. Together, these data suggest differential, state-dependent alterations in electrophysiological activity and ERK phosphorylation along the PFC-amygdala-dPAG pathway during pain, conditioned fear, and FCA.
authors.affiliation: Pharmacology and Therapeutics, NCBES Neuroscience Cluster and Centre for Pain Research, School of Medicine, National University of Ireland, Galway, Ireland.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Butler
authors.forename: Linda
authors.initials: L
authors.lastname: Nilsson-Todd
authors.forename: Carine
authors.initials: C
authors.lastname: Cleren
authors.forename: Isabelle
authors.initials: I
authors.lastname: Léna
authors.forename: René
authors.initials: R
authors.lastname: Garcia
authors.forename: David P
authors.initials: DP
authors.lastname: Finn
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001703:Biophysics; D003213:Conditioning, Psychological / Q000502:physiology*; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005239:Fear; D005557:Formaldehyde / Q000009:adverse effects; D005786:Gene Expression Regulation; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D010146:Pain / Q000473:pathology* / Q000503:physiopathology; D059408:Pain Management; D010147:Pain Measurement; D017288:Pain Threshold; D010487:Periaqueductal Gray / Q000502:physiology*; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats
chemical_list: D005557:Formaldehyde; D048049:Extracellular Signal-Regulated MAP Kinases