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Updated: Jun 27, 2026

Assessment of Morphine-induced Hyperalgesia and Analgesic Tolerance in Mice Using Thermal and Mechanical Nociceptive Modalities
Published on: July 29, 2014
Strain-specific differences in modulatory effects of morphine on peritoneal inflammation in mice
Joanna Natorska1, Barbara Plytycz
1Department of Evolutionary Immunobiology, Institute of Zoology, Jagiellonian University, R. Ingardena 6, 30-060 Kraków, Poland.
Abstract:
It has been previously shown that local administration of a high dose of morphine together with a proinflammatory agent has anti-inflammatory effects in several (but not all) strains of mice. In the present paper, behavioural and cellular consequences of morphine co-injection are compared between several strains of mice with zymosan-induced peritonitis. Males of C57C3H, Swiss, Balb/c, C57BL/6, and CBA strains were ip injected with Zymosan (40 mg/kg) and/or morphine at 0, 5, 10, 20 mg/kg without or with naltrexone pretreatment. Early stages of Zymosan-induced peritonitis were connected with intraperitoneal accumulation of leukocytes (mainly PMNs), pain symptoms (body writhes of strain-specific frequency: C57C3H>CBA>Swiss>>Balb/c-C57BL/6), and sedation (significant in Swiss and Balb/c). Morphine co-injection abolished pain symptoms at all doses in every investigated strain, and restored locomotor activity or induced hyperlocomotion in a dose- and strain-specific manner. The highest dose of morphine inhibited intraperitoneal accumulation of peritoneal leukocytes (PTLs) including polymorphonuclear cells (PMNs) in all but the CBA strain of mice. Anti-inflammatory and anti-nociceptive effects of morphine were reversed in naltrexone pre-treated animals. The pre-incubation of Swiss but not CBA leukocytes with morphine inhibited cell chemotaxis towards zymosan-activated serum. In conclusion, morphine exerts various strain-specific effects on peritonitis.
Insights
Morphine co-injection with zymosan reduced pain and leukocyte accumulation in most mouse strains, but effects varied by strain. Naltrexone reversed these morphine impacts, indicating opioid receptor involvement.
Area of Science:
- Pharmacology
- Immunology
- Neuroscience
Background:
- Local administration of high-dose morphine with a proinflammatory agent can exhibit anti-inflammatory effects.
- These effects are not consistent across all mouse strains.
- Zymosan-induced peritonitis is a model to study inflammation and pain responses.
Purpose of the Study:
- To compare the behavioral and cellular consequences of morphine co-injection during zymosan-induced peritonitis across different mouse strains.
- To investigate the dose- and strain-specific effects of morphine on pain, locomotion, and leukocyte accumulation.
- To determine the role of opioid receptors in morphine's effects using naltrexone.
Main Methods:
- Male mice from C57C3H, Swiss, Balb/c, C57BL/6, and CBA strains were injected with zymosan and/or morphine.
- Different doses of morphine (0-20 mg/kg) were administered, with or without naltrexone pretreatment.
- Behavioral assessments (pain, locomotion) and cellular analysis (leukocyte accumulation) were performed.
Main Results:
- Morphine abolished pain symptoms in all strains and affected locomotion in a dose- and strain-specific manner.
- High-dose morphine inhibited leukocyte and polymorphonuclear cell accumulation in all strains except CBA.
- Naltrexone reversed the anti-inflammatory and anti-nociceptive effects of morphine, and morphine inhibited leukocyte chemotaxis in vitro.
Conclusions:
- Morphine exerts strain-specific effects on peritonitis, impacting pain, locomotion, and inflammation.
- Opioid receptors mediate the anti-inflammatory and anti-nociceptive actions of morphine in this model.
- Mouse strain differences are critical for understanding morphine's complex effects on inflammation and pain.
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