Browsing by Subject "inflammatory pain"

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    The central amygdala to periaqueductal gray pathway comprises intrinsically distinct neurons differentially affected in a model of inflammatory pain
    (Wiley, 2018) Li, Jun-Nan; Sheets, Patrick L.; Pharmacology and Toxicology, School of Medicine
    A major population of neurons in the central nucleus of amygdala (CeA) send projections to the periaqueductal gray (PAG), a key midbrain structure that mediates coping strategies in response to threat or stress. While the CeA‐PAG pathway has proved to be a component of descending anti‐nociceptive circuitry, the functional organization of CeA‐PAG neurons remains unclear. We identified CeA‐PAG neurons in C57BL/6 mice of both sexes using intracranial injection of a fluorescent retrograde tracer into the PAG. In acute brain slices, we investigated the topographical and intrinsic characteristics of retrogradely labelled CeA‐PAG neurons using epifluorescence and whole‐cell electrophysiology. We also measured changes to CeA‐PAG neurons in the complete Freund's adjuvant (CFA) model of inflammatory pain. Neurons in the central lateral (CeL) and central medial (CeM) amygdala project primarily to different regions of the PAG. CeL‐PAG neurons consist of a relatively homogeneous population of intrinsically distinct neurons while CeM‐PAG neurons are intrinsically heterogeneous. Membrane properties of distinct CeM‐PAG subtypes are altered 1 day after induction of the CFA inflammatory pain model. Collectively, our results provide insight into pain‐induced changes to a specific population of CeA neurons that probably play a key role in the integration of noxious input with endogenous analgesia and behavioural coping response.
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    SCHWANN CELLS MODULATE THE RELEASE OF CALCITONIN GENE-RELATED PEPTIDE FROM SENSORY NEURONS
    (Office of the Vice Chancellor for Research, 2012-04-13) Meadows, Rena M.; Hingtgen, Cynthia M.
    An alteration in the interaction between Schwann cells and sensory neurons may be involved in inflammatory neuropathies associated with altered sensation and pain. The release of the peptide transmitter, calcitonin gene-related peptide (CGRP), is one method to monitor the sensitivity of a subclass of primary sensory neurons involved in pain signaling. We utilized an in vitro assay to investigate the interaction between Schwann cells and sensory neurons in an inflammatory state. Schwann cells and sensory neurons were isolated from adult mouse sciatic nerve and dorsal root ganglia, respectively, and maintained in culture. Schwann cells were exposed to HEPES buffer containing the inflammatory mediators histamine, prostaglandin E2, bradykinin, and serotonin (all 10-5 M), potassium (7 mM), and at pH 7.0 for 10 minutes. After this activation, the Schwann cells were incubated in HEPES buffer alone for 1 hour. This Schwann cell-conditioned buffer (SCCB) was collected and sensory neurons were exposed to three consecutive 10 minute incubations in HEPES buffer alone or SCCB. The amount of CGRP released during each of these incubations was measured using radioimmunoassay. Incubation with SCCB elicited a seven-fold increase in the release of CGRP compared to neurons exposed to HEPES buffer alone. The release of CGRP elicited by SCCB was abolished when neurons were exposed to SCCB containing no added calcium. After treatment with the inflammatory mediators detailed above for 10 minutes, Schwann cell lysates showed a significant decrease in six cytokines, while SCCB demonstrated an increase in interleukin-6 (IL-6) as measured by a cytokine array panel. These results suggest that during inflammation, Schwann cells release substances, which directly stimulate sensory neurons, as measured by an increase in CGRP release. These findings reinforce the importance of identifying the mechanisms underlying the interaction between Schwann cells and sensory neurons to discover novel therapeutics for treating inflammatory pain.