TY - JOUR
T1 - Molecular and electrophysiological changes in the prefrontal cortex-amygdala-dorsal periaqueductal grey pathway during persistent pain state and fear-conditioned analgesia
AU - Butler, Ryan K.
AU - Nilsson-Todd, Linda
AU - Cleren, Carine
AU - Léna, Isabelle
AU - Garcia, René
AU - Finn, David P.
N1 - Funding Information:
This work was supported by research grants from Science Foundation Ireland and the Irish Research Council for Science, Engineering, and Technology to DPF and a fellowship from the European Molecular Biology Organization to RKB. The funding bodies did not play a role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication.
PY - 2011/10/24
Y1 - 2011/10/24
N2 - 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.
AB - 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.
KW - Analgesia
KW - Context fear conditioning
KW - Field potentials
KW - Mitogen-activated protein kinase (MAPK)
KW - Pain
KW - Periaqueductal grey (PAG)
KW - Prefrontal cortex (PFC)
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U2 - 10.1016/j.physbeh.2011.05.028
DO - 10.1016/j.physbeh.2011.05.028
M3 - Article
C2 - 21683728
AN - SCOPUS:80053053690
SN - 0031-9384
VL - 104
SP - 1075
EP - 1081
JO - Physiology and Behavior
JF - Physiology and Behavior
IS - 5
ER -