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Journal of Integrative Medicine ›› 2020, Vol. 18 ›› Issue (2): 174-180.doi: 10.1016/j.joim.2020.01.002

• Original Experimental Research • Previous Articles     Next Articles

Effects of the plant-derived analgesic compounds sinomenine and salvinorin A in infant rats

Conrad J. Mascarenhasa, Ren-yu Liub, Gordon A. Barra,b,c   

  1. a. Department of Anesthesiology and Critical Care, Children’s Hospital of Philadelphia, Philadelphia 19104, USA
    b. Department of Anesthesiology and Critical Care, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
    c. Department of Psychology, University of Pennsylvania, Philadelphia, PA 19104, USA
  • Received:2019-01-25 Accepted:2019-07-03 Online:2020-03-10 Published:2020-03-18
  • Contact: Gordon A. Barr E-mail:Barrg@email.chop.edu

Objective

Premature and ill neonates undergo painful but medically necessary procedures while hospitalized. Although opiate drugs are administered as analgesics, problems associated with their side effects, tolerance, and potential dependence necessitate research into alternative pain-relieving medications. Here we test two plant-derived compounds in infant rats: sinomenine, which targets the Mas-related G-protein coupled receptor member X2 opioid receptor; and salvinorin A, which is a κ opioid receptor agonist. In adult animals both sinomenine and salvinorin A are analgesic, but neither has been tested in infants. 


Methods

We used the formalin and thermal plantar tests in rats 7- and 21-days of age (PN7; PN21) for behavioral signs of pain. In addition, brain sections were stained using Fos immunohistochemistry to examine patterns of brain activation in the midbrain periaqueductal gray and the paraventricular nucleus of the hypothalamus. 


Results

Sinomenine was analgesic in both the formalin and thermal tests on animals 21 days of age. At PN7 only the highest dose elevated response latencies in the thermal test and there were no effects of sinomenine in the formalin test. Analysis of Fos expression in the sinomenine-treated animals showed no drug effect, in contrast to the behavioral results. Salvinorin A was analgesic in the formalin test only at the highest dose at 21 days of age but not in the thermal test at either age. 


Conclusion

The increased modest effectiveness of sinomenine in older animals and the minimum salvinorin A drug effect suggest that the compounds act on sites that develop during the preweaning period (sinomenine) or after weaning (salvinorin A).

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