Contribution of amygdala CRF neurons to chronic pain. Exp Neurol 2017 Dec;298(Pt A):1-12
Date
08/24/2017Pubmed ID
28830762Pubmed Central ID
PMC5658242DOI
10.1016/j.expneurol.2017.08.010Scopus ID
2-s2.0-85027996756 (requires institutional sign-in at Scopus site) 40 CitationsAbstract
We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord. Next, we injected the CeAmy of CRF-cre mice with cre activated AAV-DREADD (Designer Receptors Exclusively Activated by Designer Drugs) vectors. Activation of CRF neurons by DREADD/Gq did not affect the impaired SIA but inhibition of CRF neurons by DREADD/Gi restored SIA and decreased allodynia in mice with neuropathic pain. The possible downstream circuitry involved in the regulation of SIA was investigated by combined injections of retrograde cre-virus (CAV2-cre) into the locus ceruleus (LC) and cre activated AAV-diphtheria toxin (AAV-FLEX-DTX) virus into the CeAmy. The viral injections were followed by a sciatic nerve constriction ipsilateral or contralateral to the injections. Ablation of amygdala projections to the LC on the side of injury but not on the opposite side, completely restored SIA, decreased allodynia and decreased ΔFosB expression in the spinal cord in mice with neuropathic pain. The possible lateralization of SIA impairment to the side of injury was confirmed by an experiment in which unilateral inhibition of the LC decreased SIA even in uninjured mice. The current view in the field of pain research attributes the process of pain chronification to abnormal functioning of descending pain inhibition. Our results demonstrate that the continuous activity of CRF neurons brought about by persistent pain leads to impaired SIA, which is a symptom of dysregulation of descending pain inhibition. Therefore, an over-activation of amygdala CRF neurons is very likely an important contributing factor for pain chronification.
Author List
Andreoli M, Marketkar T, Dimitrov EAuthor
Matthew Andreoli MD Assistant Professor in the Family Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AmygdalaAnimals
Chronic Pain
Corticotropin-Releasing Hormone
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurons
Pain Measurement
Pain Threshold
