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07:23
Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Peripheral endothelin B receptor agonist-induced antinociception involves endogenous opioids in mice
Phuong N Quang1, Brian L Schmidt
1UCSF School of Dentistry Oral and Craniofacial Sciences Graduate Program, USA UCSF Helen Diller Family Comprehensive Cancer Center, USA Department of Oral and Maxillofacial Surgery, USA.
Pain
|March 9, 2010
Summary
Activating endothelin B receptors (ETBR) with BQ-3020 reduces oral cancer pain in mice by increasing beta-endorphin production. This suggests ETBR agonism as a potential pain management strategy for carcinoma.
Area of Science:
- Oncology
- Pain Research
- Molecular Biology
Background:
- Endothelin-1 (ET-1) contributes to cancer pain, primarily via ETAR activation.
- The role of endothelin B receptor (ETBR) in cancer pain and its interaction with endogenous analgesia remains unclear.
Purpose of the Study:
- To investigate the effects of ETBR activation on carcinoma pain.
- To explore the involvement of endogenous opioid analgesia in ETBR-mediated pain modulation.
Main Methods:
- Utilized an orthotopic oral squamous cell carcinoma (SCC) mouse model.
- Analyzed mRNA expression of ET-1 and ETBR in SCC cells versus normal oral keratinocytes (NOK).
- Administered ETBR agonist (BQ-3020) and antagonist (BQ-788) intratumorally; assessed pain via paw withdrawal thresholds.
- Investigated the role of opioid receptors using naloxone methiodide and CTOP.
Main Results:
- SCC cells showed increased ET-1 and decreased ETBR expression compared to NOK.
- ETBR agonist BQ-3020 significantly increased beta-endorphin production in SCC cells.
- Intratumoral BQ-3020 administration attenuated cancer pain by ~50% for 3 hours.
- ETBR antagonist BQ-788 had no effect on cancer pain.
- Opioid receptor antagonists reversed BQ-3020-induced antinociception.
Conclusions:
- Peripheral ETBR activation attenuates carcinoma pain.
- This effect is mediated by increased beta-endorphin release from SCC cells.
- The antinociception involves the modulation of peripheral opioid receptors within the tumor microenvironment.
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