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Analgesia in mice with experimental meningitis reduces pain without altering immune parameters
Sarah Mundt1, Marcus Groettrup1,2, Michael Basler1,2
1Division of Immunology, Department of Biology, University of Konstanz, Konstanz, Germany.
Abstract:
Intracranial lymphocytic choriomeningitis virus (LCMV) infection is a widely used animal model to study virus-induced cytotoxic T cell (CTL) mediated meningitis and immunopathology. Nevertheless, this model causes severe pain and distress in mice, especially at later stages of the disease. Therefore, new treatment regimens to improve animal welfare have to be developed. In this study, we subcutaneously implanted ALZET® osmotic pumps continuously releasing buprenorphine to reduce pain in mice with LCMV-induced meningitis. Thereby, mice treated with buprenorphine demonstrated strongly reduced symptoms of pain. However, the LCMV-specific cytotoxic T cell response and the immune cell infiltration into the central nervous system (CNS) were unchanged in analgesia treated mice indicating that the LCMV-induced immune response was not altered in these mice. Taken together, we demonstrate that in this animal model for meningitis continuous buprenorphine treatment improves animal welfare without affecting the immune response.
Insights
Continuous buprenorphine treatment in mice with lymphocytic choriomeningitis virus (LCMV) meningitis reduced pain symptoms. This pain management strategy improved animal welfare without altering the virus-specific cytotoxic T cell response or central nervous system immune infiltration.
Area of Science:
- Neuroimmunology
- Virology
- Animal Welfare Science
Background:
- Intracranial lymphocytic choriomeningitis virus (LCMV) infection is a common model for studying meningitis and immunopathology.
- This LCMV model causes significant pain and distress in mice, necessitating improved animal welfare strategies.
- Developing effective analgesia is crucial for ethical research and reliable experimental outcomes.
Purpose of the Study:
- To evaluate the efficacy of continuous buprenorphine administration in mitigating pain in mice with LCMV-induced meningitis.
- To determine if buprenorphine treatment affects the LCMV-specific cytotoxic T cell (CTL) response.
- To assess the impact of analgesia on immune cell infiltration into the central nervous system (CNS).
Main Methods:
- Subcutaneous implantation of ALZET® osmotic pumps for continuous buprenorphine release in mice.
- Induction of intracranial LCMV infection to model meningitis.
- Assessment of pain symptoms in treated and untreated mice.
- Analysis of LCMV-specific CTL responses and CNS immune cell infiltration.
Main Results:
- Mice treated with buprenorphine exhibited significantly reduced signs of pain and distress.
- No significant alterations were observed in the LCMV-specific cytotoxic T cell response in buprenorphine-treated mice.
- Immune cell infiltration into the CNS remained unchanged despite analgesia treatment.
Conclusions:
- Continuous buprenorphine administration effectively alleviates pain in the LCMV meningitis mouse model, thereby improving animal welfare.
- This analgesic approach does not interfere with the host's antiviral immune response, including CTL activity and CNS immune cell infiltration.
- Buprenorphine is a suitable treatment for enhancing animal welfare in LCMV meningitis research without confounding experimental results.
