Indiana University-Purdue University Indianapolis (IUPUI) / Currently, changes to endogenous opioid circuits in various pain
modalities, including surgical and neuropathic pain, remain unclear. Dynorphin,
which is released by prodynorphin-expressing neurons (Pdyn+ neurons), is the
endogenous opioid ligand to kappa opioid receptors (KOR). Moreover, a recent
study has shown an increase in prodynorphin (Pdyn) mRNA expression in the
prelimbic cortex (PL) in a mouse model of chronic pain. However, alterations in
the activity of PL Pdyn-expressing neurons (PLPdyn+ neurons) in postoperative
and chronic pain have never been explored. Firstly, I found that the population of
PLPdyn+ neurons consists of both pyramidal and inhibitory subtypes. Secondly, I
found that one day after surgical incision of the mouse hind paw, the excitability
of pyramidal PLPdyn+ neurons was increased in both male and female mice, while
the excitability of inhibitory PLPdyn+ neurons was unchanged. However, when
postoperative pain behavior subsided, inhibitory PLPdyn+ neurons were
hyperexcitable in male mice, while pyramidal PLPdyn+ neurons were hypoexcitable
in female mice. Lastly, I dissected electrophysiological changes to PLPdyn+
neurons in the spared nerve injury (SNI) model of chronic neuropathic pain. At
both early and late stages of SNI pain development, increased excitability of
pyramidal PLPdyn+ neurons was detected in both male and female mice. However,
in both male and female mice, the excitability of inhibitory PLPdyn+ neurons decreased 3 days after SNI but was conversely increased when measured 14
days after SNI. My findings suggest that different subtypes of PLPdyn+ neurons
manifest distinct alterations in the development of different pain modalities in a
sex-specific manner.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/30794 |
| Date | 11 1900 |
| Creators | Zhou, Shudi |
| Contributors | Atwood, Brady K., Sheets, Patrick L., McKinzie, David L., Truitt, William A., Jin, Xiaoming |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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