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Persistent pain intensifies the recall of already consolidated fear memories
Author(s) -
Dimitrov Eugene
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1076.5
Subject(s) - neuropathic pain , anesthesia , fear conditioning , conditioning , allodynia , medicine , mood , threshold of pain , anxiety , stimulus (psychology) , hyperalgesia , psychology , nociception , psychiatry , statistics , receptor , mathematics , psychotherapist
The deleterious impact of chronic pain on learning, memory and mood is well documented. Long‐lasting pain leads to anxiety, depression and negatively impairs learning and formation of new memories. We hypothesized that chronic pain may affect even memories that were established before the onset of pain. Mice underwent a classic auditory fear conditioning that included 30 seconds 75 dB tone as a conditioned stimulus (CS) that was paired with 2 seconds 1 mA electric foot shock as unconditioned stimulus (US). Sciatic nerve constriction by inserting a small plastic tube around the left sciatic nerve was used to induce neuropathic pain 48 hours after the fear conditioning. This nerve constriction, also called “cuffing”, reliably produced mechanical allodynia that lasted for the duration of the experiments. Fear recall was measured by exposing the mice to the CS and recording their activity for five minutes. The time mice were completely immobile (freezing time) was expressed as a percent. Two sessions of fear recall were conducted, one 14 days and second 28 days after the initiation of neuropathic pain. Mice with neuropathic pain showed an increased percent of time freezing to CS (sham group with 22.7% ± 1.4 versus an average of 38.2% ± 4.3 freezing time for the pain group, t 36 =3.9, P<0.001). The cuffed mice once again spent more time freezing when retested 28 days after the beginning of pain (the average freezing time was 22.9% ± 2.9 for the shams versus 49.5% ± 4.9 of the cuffed group, t 36 = 4.8, P< 0.001). In the next experiment the sciatic nerve constriction was applied two weeks after fear conditioning. These mice showed increased fear response to the CS 14 days after the onset of pain or 28 days after the fear conditioning took place (the freezing time of the sham group was 44.6% ± 6.5 versus the cuffed group with 69.5% ± 5.4 freezing time, t 18 = 2.9, P<0.001). When tested for anxiety and depression, the experimental groups did not display any increased anxiety‐like or depression‐like behavior in comparison to the control groups. However, the Sholl analysis of the pyramidal neurons in basolateral amygdala of mice with neuropathic pain showed increased dendritic length (the average dendritic length was 701.9 μm ± 40.1 in sham group versus 955.7 μm ± 46.2 in cuffed group, df 25 =2.7, P<0.02). In conclusion, our studies provide evidence for impact of persistent pain on already consolidated fear memories. Very likely the underlying mechanism for this phenomenon is increased dendritic plasticity of the pyramidal neurons brought by overall decreased inhibitory tone in basolateral amygdala during persistent pain. It is possible that the increased fear recall to already consolidated fear memory is a harbinger for a later development of anxiety and depression symptoms that are typical for chronic pain. Support or Funding Information Grant # 5R01MH105528‐04