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Proinflammatory effects of morphine in the rat adjuvant arthritis model
J R Earl1, A W Claxson, D R Blake
1Inflammation Research Group, London Hospital Medical College, England.
Abstract:
Morphine has been shown to alter various aspects of the immune response. We examined its effect on progression of the T-cell-mediated model, rat adjuvant arthritis. Saline, morphine or the opioid antagonist naloxone were administered to male Wistar rats via subcutaneous osmotic pumps implanted three days prior to adjuvant disease induction by an intra-dermal injection of Mycobacterium tuberculosis in oil. The time of disease onset was found to be accelerated (day 11) for the morphine group as compared to the saline control (day 13). In addition morphine produced a significant increase in paw swelling (days 13 and 14), bone demineralization and bone erosions. A significant decrease in body weight as compared to the saline control was also observed. Naloxone had no significant effect on the degree of the inflammation seen, although like morphine it significantly increased bone demineralization and bone erosions as assessed by radiography.
Insights
Morphine accelerated the onset and severity of rat adjuvant arthritis, a T-cell-mediated disease. This opioid analgesic also worsened bone erosion and decreased body weight in the arthritis model.
Area of Science:
- Immunology
- Pharmacology
- Rheumatology
Background:
- Opioids like morphine can modulate immune system functions.
- Rat adjuvant arthritis is a well-established model for studying T-cell-mediated inflammatory diseases.
Purpose of the Study:
- To investigate the effects of morphine on the progression of T-cell-mediated rat adjuvant arthritis.
- To evaluate the impact of the opioid antagonist naloxone on this arthritis model.
Main Methods:
- Male Wistar rats were administered saline, morphine, or naloxone via osmotic pumps.
- Adjuvant arthritis was induced by intradermal injection of Mycobacterium tuberculosis in oil.
- Disease onset, paw swelling, body weight, and bone changes (demineralization, erosions) were assessed.
Main Results:
- Morphine significantly accelerated arthritis onset (day 11 vs. day 13) and increased paw swelling.
- Morphine administration led to significant bone demineralization and erosions, along with decreased body weight.
- Naloxone did not affect inflammation but significantly increased bone demineralization and erosions, similar to morphine.
Conclusions:
- Morphine exacerbates T-cell-mediated arthritis progression and associated bone damage in rats.
- The opioid antagonist naloxone shares some of morphine's detrimental effects on bone in this model.
- These findings highlight opioid-induced immunomodulation impacting inflammatory and destructive processes in arthritis.