Sex differences in the amygdaloid projections to the ventrolateral periaqueductal gray and their activation during inflammatory pain in the rat

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dc.contributor.authorCantu, Daisy J.
dc.contributor.authorKaur, Sukhbir
dc.contributor.authorMurphy, Anne Z,
dc.contributor.authorAveritt, Dayna L.
dc.creator.orcidhttps://orcid.org/0000-0001-8345-4988
dc.date.accessioned2023-02-27T15:49:47Z
dc.date.available2023-02-27T15:49:47Z
dc.date.issued2022
dc.descriptionThis research was supported by National Institutes of Health grants DA16272 and AR49555 awarded to AZM and the STC Program of NSF IBN-9876754.
dc.description.abstractPreclinical and clinical studies have reported sex differences in pain and analgesia. These differences may be linked to anatomical structures of the central nervous system pain modulatory circuitry, and/or hormonal milieu. The midbrain periaqueductal gray (PAG) is a critical brain region for descending inhibition of pain. The PAG projects to the rostral ventromedial medulla (RVM), which projects bilaterally to the spinal cord to inhibit pain. In addition to pain, this descending circuit (or pathway) can be engaged by endogenous opioids (i.e., endorphins) or exogenous opioids (i.e., morphine), and we have previously reported sex differences in the activation of this circuit during pain and analgesia. Forebrain structures, including the amygdala, project to and engage the PAG-RVM circuit during persistent inflammatory pain. However, there are limited studies in females detailing this amygdalar-PAG pathway and its involvement during persistent inflammatory pain. The objective of the present study was to delineate the neural projections from the amygdala to the PAG in male and female rats to determine if they are sexually distinct in their anatomical organization. We also examined the activation of this pathway by inflammatory pain and the co-localization of receptors for estrogen. Injection of the retrograde tracer fluorogold (FG) into the ventrolateral PAG (vlPAG) resulted in dense retrograde labeling in both the central amygdala (CeA) and medial amygdala (MeA). While the number of CeA-vlPAG neurons were comparable between the sexes, there were more MeA-vlPAG neurons in females. Inflammatory pain resulted in greater activation of the amygdala in males; however, females displayed higher Fos expression within CeA-vlPAG projection neurons. Females expressed higher ERĪ± in the MeA and CeA and the same was true of the projection neurons. Together, these data indicate that although the MeA-vlPAG projections are denser in females, inflammatory pain does not significantly activate these projections. In contrast, inflammatory pain resulted in a greater activation of the CeA-vlPAG pathway in females. As females experience a greater number of chronic pain syndromes, the CeA-vlPAG pathway may play a facilitatory (and not inhibitory) role in pain modulation.en_US
dc.identifier.citationThis is the abstract for an article that is available at https://doi.org/10.1016/j.jchemneu.2022.102123. Recommended citation: Cantu, D. J., Kaur, S., Murphy, A. Z., & Averitt, D. L. (2022). Sex differences in the amygdaloid projections to the ventrolateral periaqueductal gray and their activation during inflammatory pain in the rat. Journal of Chemical Neuroanatomy, 124, 102123. This item has been deposited in accordance with publisher copyright and licensing terms and with the authorā€™s permission.en_US
dc.identifier.urihttps://hdl.handle.net/11274/14521
dc.identifier.urihttps://doi.org/10.1016/j.jchemneu.2022.102123
dc.language.isoen_USen_US
dc.publisherElsevieren_US
dc.subjectAmygdalaen_US
dc.subjectPAGen_US
dc.subjectRetrograde tract-tracingen_US
dc.subjectFosen_US
dc.subjectEstrogen receptoren_US
dc.titleSex differences in the amygdaloid projections to the ventrolateral periaqueductal gray and their activation during inflammatory pain in the raten_US
dc.typeAbstracten_US

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