Dissertation
A mechanistic study of hyperbaric oxygen-induced antinociception in a rat model of neuropathic pain
Doctor of Philosophy (PhD), Washington State University
08/2015
Handle:
https://hdl.handle.net/2376/6200
Abstract
Hyperbaric oxygen (HBO2) has been shown to produce pain relief in patients with chronic pain and long-lasting antinociception in experimental animals. However, the Food and Drug Administration has not approved HBO2 as a treatment for pain, because clinical evidence of its efficacy is lacking and its mechanism of action is still not well understood. Thus, the aim of this project was to further explore the mechanism of HBO2-induced antinociception in a rat model of neuropathic pain.
We hypothesized that HBO2 produced a long-lasting antinociception via a nitric oxide (NO)-mediated supraspinal pathway. To test the hypothesis, male Sprague-Dawley rats were used and repeatedly injected with paclitaxel to develop neuropathic pain. To examine the effect of HBO2 on the neuropathic pain, subgroups of rats received a single 60-min HBO2 treatment or four daily 60-min treatments after paclitaxel injections. To study the role of supraspinal NO in HBO2-induced antinociception, an nNOS inhibitor S-methyl-L-thiocitrulline (SMTC) was delivered into the cerebroventricular system during HBO2 treatment. To study the involvement of the rostral ventromedial medulla (RVM) in HBO2 antinociceptive mechanism, the RVM of the rat was inactivated with microinjections of lidocaine prior to HBO2 treatment. Both mechanical and cold allodynic responses of the rat were tested every other day for a month to assess the development of neuropathic pain and the effects of different treatments. In addition, the gene and the protein expression of nNOS in the periaqueductal gray (PAG) and the RVM were examined to examine the effect of HBO2 on NO production in these two structures.
The results of the present project demonstrate that HBO2 significantly reduced paclitaxel-induced mechanical and cold allodynia for at least three weeks. Intracerebroventricular infusion of 1 mM SMTC suppressed the antinociceptive effect against mechanical but not cold allodynia, but inactivation of the RVM with 2% w/v lidocaine suppressed the antinociceptive effect against cold but not mechanical allodynia. In addition, HBO2 treatment increased the protein expression of nNOS in the PAG and the number of nNOS-positive neurons in the RVM. Collectively, these results suggest that the HBO2-induced antinociceptive mechanism may involve NO-mediated neuronal activity in the PAG-RVM pain-regulating system.
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Details
- Title
- A mechanistic study of hyperbaric oxygen-induced antinociception in a rat model of neuropathic pain
- Creators
- Yangmiao Zhang
- Contributors
- RAYMOND QUOCK (Advisor) - Washington State University, Psychology, Department ofAmber V Buhler (Advisor)REBECCA MIRIAM CRAFT (Advisor) - Washington State University, Psychology, Department ofMichael Monte Morgan (Advisor) - Washington State University, Psychology, Department of
- Awarding Institution
- Washington State University
- Academic Unit
- Program in Neuroscience
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 98
- Identifiers
- 99900908441401842
- Language
- English
- Resource Type
- Dissertation