The role of cytokines in the nervous system during chronic pain

1997 Fiscal Year Final Research Report Summary

• Project/Area Number: 08671766
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Anesthesiology/Resuscitation studies
• Research Institution: DOKKYO UNIVERSITY,SCHOOL OF MEDICINE
• Principal Investigator: TAKANO Yoshito DOKKYO UNIVERSITY,SCHOOL OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 助教授 (10134701)
• Project Period (FY): 1996 – 1997
• Keywords: chronic pain / spinal cord / inflammatory hyperalgesia / interleukin-1beta / NMDA receptor / nitric oxide / tyrosine kinase

Research Abstract

Interleukin-l beta (IL) is one of cytokines which are secreted from immune cells or glial cells in the nervous system. It is speculated that IL could play an important role in the transmission of pain in the spinal cord, and the action of IL is known to involve the activation of tyrosine kinase in the neuron. Thus, in the present study, the author investigated the effect of IL administered to the spinal cord on the pain threshold in rat, and also investigated the effect of tyrosine kinase inhibitor on the development of inflammatory hyperalgesia induced by the inoculation of the mixture of carrageenan and kaolin (CK) to the tail joint. Male Sprague-Dawley rats with chronically implanted intrathecal catheters were used. The doses of IL given spinally were 10.100, or 1000 ng per rat. In the separate group of animals, IL lOOng was administered with MK-801, 3.4 mug, L-NAME 2.71 mug, or Methylene Blue lO mug, In the inflammatory group, Lavendustin-A which is a selective tyrosine kinase inhibitor was intrathecally administered before the inoculation of CK.To examine the pain thresholds, hot plate test (HP, Paw Pressure test (PP) and formalin test were applied. Intrathecal IL showed a hyperalgesic effect in PP.The largest effect was seen when lOOng was administered. This effect was completely abolished by a co-administration of MK-801, L-NAME or Methylene Blue. In the inflammatory rats, hyperalgesa was observed 4 hours after CK inoculation when the formalin test was used Lavendustion-A prevented the development of inflammatory hyperalgesia. These results suggest that the hyperalgesic effect of IL involves spinal NMDA receptor and nitric oxide system in the dorsal horn and inflammatory hyperalgesia is speculated to have the involvement of IL and tyrosine kinase activity.