Transcriptomic and behavioural characterisation of a mouse model of burn pain identify the cholecystokinin 2 receptor as an analgesic target

Yin, Kathleen, Deuis, Jennifer R., Lewis, Richard J. and Vetter, Irina (2016) Transcriptomic and behavioural characterisation of a mouse model of burn pain identify the cholecystokinin 2 receptor as an analgesic target. Molecular Pain, 12 1-13. doi:10.1177/1744806916665366


Author Yin, Kathleen
Deuis, Jennifer R.
Lewis, Richard J.
Vetter, Irina
Title Transcriptomic and behavioural characterisation of a mouse model of burn pain identify the cholecystokinin 2 receptor as an analgesic target
Journal name Molecular Pain   Check publisher's open access policy
ISSN 1744-8069
Publication date 2016-08-28
Sub-type Article (original research)
DOI 10.1177/1744806916665366
Open Access Status DOI
Volume 12
Start page 1
End page 13
Total pages 13
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
Burn injury is a cause of significant mortality and morbidity worldwide and is frequently associated with severe and long-lasting pain that remains difficult to manage throughout recovery. We characterised a mouse model of burn-induced pain using pharmacological and transcriptomic approaches. Mechanical allodynia elicited by burn injury was partially reversed by meloxicam (5 mg/kg), gabapentin (100 mg/kg) and oxycodone (3 and 10 mg/kg), while thermal allodynia and gait abnormalities were only significantly improved by amitriptyline (3 mg/kg) and oxycodone (10 mg/kg). The need for relatively high opioid doses to elicit analgesia suggested a degree of opioid resistance, similar to that shown clinically in burn patients. We thus assessed the gene expression changes in dorsal root ganglion neurons and pathophysiological mechanisms underpinning burn injury-induced pain using a transcriptomic approach. Burn injury was associated with significantly increased expression of genes associated with axon guidance, neuropeptide signalling, behavioural defence response and extracellular signalling, confirming a mixed neuropathic and inflammatory aetiology. Notably, among the pain-related genes that were upregulated post-injury was the cholecystokinin 2 receptor (Cckbr), a G protein-coupled receptor known as a pain target involved in reducing opioid effectiveness. Indeed, the clinically used cholecystokinin receptor antagonist proglumide (30 mg/kg) was effective at reversing mechanical allodynia, with additional analgesia evident in combination with low-dose oxycodone (1 mg/kg), including significant reversal of thermal allodynia. These findings highlight the complex pathophysiological mechanisms underpinning burn injury-induced pain and suggest that cholecystokinin-2 receptor antagonists may be useful clinically as adjuvants to decrease opioid requirements and improve analgesic management.
Keyword Burn-induced pain
Transcriptome
Dorsal root ganglion neurons
Animal models
Proglumide
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Pharmacy Publications
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 08 Nov 2016, 00:18:46 EST by Susan Allen on behalf of Institute for Molecular Bioscience