Spinal and Peripheral GABA-A and B Receptor Agonists for the Alleviation of Mechanical Hypersensitivity following Compressive Nerve Injury in the Rat

백서에서 신경압박 손상에 의해 유발된 과민반응에서 척추 및 말초 GABA-A와 B 수용체 작용제에 의한 완화효과

  • Jeon, Young Hoon (Departments physiology and Yonsei University College of Medicine) ;
  • Yoon, Duck Mi (Departments Anesthesiology & Pain Medicine Yonsei University College of Medicine) ;
  • Nam, Taick Sang (Departments physiology and Yonsei University College of Medicine) ;
  • Leem, Joong Woo (Departments physiology and Yonsei University College of Medicine) ;
  • Paik, Gwang Se (Departments physiology and Yonsei University College of Medicine)
  • 전영훈 (연세대학교 의과대학 생리학교실) ;
  • 윤덕미 (연세대학교 의과대학 마취통증의학교실) ;
  • 남택상 (연세대학교 의과대학 생리학교실) ;
  • 임중우 (연세대학교 의과대학 생리학교실) ;
  • 백광세 (연세대학교 의과대학 생리학교실)
  • Received : 2006.01.19
  • Accepted : 2006.03.31
  • Published : 2006.06.30

Abstract

Background: This study was conducted to investigate the roles of the spinal and peripheral ${\gamma}$-aminobutyric acid (GABA)- ergic systems for the mechanical hypersensitivity produced by chronic compression of the dorsal root ganglion (CCD). Methods: CCD was performed at the left 5th lumbar dorsal root ganglion. The paw withdrawal threshold (PWT) to von Frey stimuli was measured. The mechanical responsiveness of the lumbar dorsal horn neurons was examined. GABAergic drugs were delivered with intrathecal (i.t.) or intraplantar (i.pl.) injection or by topical application onto the spinal cord. Results: CCD produced mechanical hypersensitivity, which was evidenced by the decrease of the PWT, and it lasting for 10 weeks. For the rats showing mechanical hypersensitivity, the mechanical responsiveness of the lumbar dorsal horn neurons was enhanced. A similar increase was observed with the normal lumbar dorsal horn neurons when the GABA-A receptor antagonist bicuculline was topically applied. An i.t. injection of GABA-A or GABA-B receptor agonist, muscimol or baclofen, alleviated the CCD-induced hypersensitivity. Topical application of same drugs attenuated the CCD-induced enhanced mechanical responsiveness of the lumbar dorsal horn neurons. CCD-induced hypersensitivity was also improved by low-dose muscimol applied (i.pl.) into the affected hind paw, whereas no effects could be observed with high-dose muscimol or baclofen. Conclusions: The results suggest that the neuropathic pain associated with compression of the dorsal root ganglion is caused by hyperexcitability of the dorsal horn neurons due to a loss of spinal GABAergic inhibition. Peripheral application of low-dose GABA-A receptor agonist can be useful to treat this pain.

Keywords

Acknowledgement

Supported by : 연세대학교

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