Antinociceptive effects of synthetic tetracycline compound and influence of Cx3cr1 in inflammatory pain

Abstract

Tetracycline compounds are broad‐spectrum antibiotics used against different bacterial infectious diseases. Synthetic tetracycline compounds have been developed and are able to reduce infection as well as inflammation. However, the effect on alleviation of pain, and more specifically reduction of inflammatory pain, has not been investigated. The goal of the study is to evaluate the effect of synthetic tetracycline compounds using an inflammatory pain model and mechanical and cold allodynia responses. The formalin test (10 μl at 2.5 % intraplantar) was use to evaluate pain threshold differences between male wild‐type C57BL/6 mice and male GFP Cx3cr1 +/− mice. First, our preliminary data demonstrate that male GFP Cx3cr1 +/− mice show lower pain threshold in both (acute and inflammatory) phases of the formalin test. Second, we evaluated the effect of a synthetic tetracycline compound on inflammatory pain and on mechanical and cold allodynia. Our data indicate that mechanical and cold allodynia remains unchanged after administration of a synthetic tetracycline compound meaning values are similar to baseline levels. However, synthetic tetracycline compound lower pain threshold in both phases of the formalin test from 4 hours up to 20 hours after its administration and showed antinociceptive effects to mechanical and cold allodynia following the formalin test (60 minutes after injection of formalin). Moreover, mechanical and cold allodynia responses return to baseline levels 2 hours after the formalin test. These results demonstrate potential antinociceptive properties of synthetic tetracycline compound with long lasting effect up to 20 hours after its administration. Further studies are needed to investigate the mechanism underlying this antinociceptive effect of synthetic tetracycline compounds. We will also evaluate potential stronger antinociceptive effect of the synthetic tetracycline compound in Cx3cr1 +/− male mice and evaluate if there is any gender specific differences. Antinociceptive properties of synthetic tetracycline compound could be a great alternative avenue to relieve inflammatory pain and improve alleviation of pain in patients.Support or Funding InformationFunded by grant from NIAAA 021142 (SEB) and funded by Texas Tech University Health Sciences Center School of Medicine grant 121035 (JG).