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Imbalance in the spinal serotonergic pathway induces aggravation of mechanical allodynia and microglial activation in carrageenan inflammation

  • Junxiu, Jin (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Dong Ho, Kang (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Jin, Jeon (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Hyung Gon, Lee (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Woong Mo, Kim (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Myung Ha, Yoon (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School) ;
  • Jeong Il, Choi (Department of Anesthesiology and Pain Medicine, Chonnam National University Hospital, Chonnam National University Medical School)
  • Received : 2022.08.23
  • Accepted : 2022.10.18
  • Published : 2023.01.01

Abstract

Background: This study investigated the effect of an excess and a deficit of spinal 5-hydroxytryptamine (5-HT) on the mechanical allodynia and neuroglia activation in a rodent pain model of carrageenan inflammation. Methods: Male Sprague-Dawley rats were implanted with an intrathecal (i.t.) catheter to administer the drug. To induce an excess or deficit of 5-HT in the spinal cord, animals were given either three i.t. 5-HT injections at 24-hour intervals or a single i.t. injection of 5,7-dihydroxytryptamine (5,7-DHT) before carrageenan inflammation. Mechanical allodynia was measured using the von Frey test for 0-4 hours (early phase) and 24-28 hours (late phase) after carrageenan injection. The changes in the activation of microglia and astrocyte were examined using immunofluorescence of the dorsal horn of the lumbar spinal cord. Results: Both an excess and a deficit of spinal 5-HT had no or a minimal effect on the intensity of mechanical allodynia during the early phase but prevented the attenuation of mechanical allodynia during the late phase, which was observed in animals not treated with i.t. 5-HT or 5,7-DHT. Animals with an excess or deficit of 5-HT showed stronger activation of microglia, but not astrocyte, during the early and late phases, than did normal animals. Conclusions: Imbalance in the descending 5-HT pathway in the spinal cord could aggravate the mechanical allodynia and enhance the activation of microglia, suggesting that the spinal 5-HT pathway plays an essential role in maintaining the nociceptive processing in balance between facilitation and inhibition in inflammatory pain caused by carrageenan inflammation.

Keywords

Acknowledgement

This work was supported by a grant (BCRI20040) from Chonnam National University Hospital Biomedical Research Institute and funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HR20C0021).

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