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Updated: Jun 6, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Nociceptive behavior following hindpaw burn injury in young rats: response to systemic morphine
Shuxing Wang1, Lin Zhang, Yuxin Ma
1MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Insights
A new burn injury model in young rats effectively mimics pain responses and molecular changes seen in pediatric burn patients. This model helps study pain mechanisms and differences between young and adult rats.
Area of Science:
- Pain research
- Animal models of injury
- Pediatric pain management
Background:
- Pediatric burn injury pain management remains a significant clinical challenge.
- Understanding age-specific pain mechanisms is crucial for effective treatment.
Purpose of the Study:
- To establish a reliable burn injury model in young rats (3-4 weeks old).
- To investigate pain behaviors and molecular changes following burn injury in young rats.
- To compare pain development and morphine response in young versus adult burn-injured rats.
Main Methods:
- A burn injury was induced using a hot water bath (85°C, 12 seconds) on the hindpaw of young rats under anesthesia.
- Nociceptive behaviors, including mechanical allodynia and thermal hyperalgesia, were assessed.
- Spinal cord dorsal horn tissue was analyzed for changes in receptor and enzyme expression.
- The efficacy of dextromethorphan, an N-methyl-D-aspartate (NMDA) receptor antagonist, was evaluated.
Main Results:
- Burn injury induced significant mechanical allodynia and thermal hyperalgesia in young rats.
- Upregulation of NMDA receptor subunit NR1, Akt1, Akt2, and PKCγ was observed in the spinal cord.
- Downregulation of neuronal nitric oxide synthase (NOS) and glycogen synthase kinase-3β occurred.
- Dextromethorphan treatment attenuated burn injury-induced pain behaviors.
- Young rats did not exhibit spontaneous tolerance to morphine's analgesic effects, unlike adult rats.
Conclusions:
- This young rat burn injury model is suitable for studying nociception mechanisms.
- The model allows for differentiation of burn injury sequelae between young and adult rats.
- Findings suggest age-dependent differences in pain development and opioid tolerance post-burn injury.
Objective:
Develop a burn injury model in young age rats.
Background:
Management of pain after burn injury in pediatric patients is an unresolved clinical issue.
Methods:
A burn injury model in young rats of 3-4 weeks old was developed by briefly immersing the dorsal part of the right hindpaw in a hot water bath (85°C) for 12 seconds under pentobarbital anesthesia.
Results:
Burn injury, but not sham control, induced nociceptive behaviors (mechanical allodynia, thermal hyperalgesia) when examined on post-injury day 2, 4, and 7. In burn-injured rats, there was the upregulated expression of the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor, Akt1, Akt2, and protein kinase C γ (PKCγ), but downregulated expression of neuronal nitric oxide synthase (NOS), inducible NOS, and glycogen synthase kinase-3β, within the spinal cord dorsal horn ipsilateral to burn injury. Moreover, intraperitoneal administration of a clinically available NMDA receptor antagonist dextromethorphan (30 mg/kg, once daily × 7 days beginning on day 7 after burn injury) attenuated mechanical allodynia and thermal hyperalgesia in burn-injured rats. Different from our previous finding in adult burn-injured rats; however, burn injury in young rats of this age did not spontaneously shift the morphine antinociceptive response curve to the right within the dose range used in the study when exposed to morphine for the first time, suggesting that the development of intrinsic tolerance to morphine antinociception may be different from adult rats following burn injury.
Conclusions:
Our data suggest that this model may be used to explore the mechanisms of burn injury-induced nociception in young rats and to differentiate the sequelae from burn injury between adult and young rats under certain experimental conditions.
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