|
|
Glycine transporter inhibitors as a potential therapeutic strategy for chronic pain with memory impairment.| Authors: | Mitsuo Tanabe, Keiko Takasu, Sachiko Yamaguchi, Daisuke Kodama, Hideki Ono | | Language: | Eng. | | Date: | 23-04-2008 | | Journal: | Anesthesiology
(1528-1175)
| | Release: | Anesthesiology. 2008 May;108(5):929-37 | |
|
|
Abstract:
|
BACKGROUND:
Impaired excitatory and inhibitory balance in the spinal dorsal horn has a crucial role in the pathophysiology of chronic pain. The authors addressed the therapeutic impact of increasing spinal glycine applied exogenously or via blockade of glycine transporter 1 using its selective inhibitors sarcosine and N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine on neuropathic and inflammatory pain in mice.
METHODS:
Mice with thermal and mechanical hypersensitivity after partial ligation of the sciatic nerve (Seltzer model) or mice with mechanical hypersensitivity after streptozotocin injection received intrathecal injection of glycine, sarcosine, and N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine. These drugs were also intrathecally injected in mice to assess their effects on formalin-evoked nociceptive behaviors. The supraspinal effect of blockade of glycine transporter 1 was studied on tetanus-induced long-term potentiation of the Schaffer-collateral synapses in hippocampal slices prepared from Seltzer model mice.
RESULTS:
Glycine, sarcosine, and N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine ameliorated thermal and mechanical hypersensitivity in Seltzer model mice, and reduced mechanical hypersensitivity in streptozotocin-injected diabetic mice. Moreover, they selectively inhibited the second phase of formalin-evoked licking/biting behavior. In hippocampal slices prepared from Seltzer model mice, long-term potentiation was maintained at a significantly lower level than that in sham-treated mice. Such impairment of long-term potentiation was never observed when it was induced in the presence of N-[3-(4'-fluorophenyl)-3-(4'-phenylphenoxy)propyl]sarcosine.
CONCLUSIONS:
An increase in endogenous glycine via glycine transporter 1 blockade not only results in a net inhibitory influence on pain transmission at the spinal level but also supraspinally relieves decreased synaptic efficacy presumably related to cognitive disturbance often described in patients with chronic pain.
| | Copyright: | Anesthesiology
Laboratory of CNS Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho-ku, Nagoya, Japan. mitana@phar.nagoya-cu.ac.jp | | Full text: | | | Terms: | Acute Disease, Analgesics, Animals, Diabetes Mellitus, Experimental, Diabetic Neuropathies, Glycine, Glycine Plasma Membrane Transport Proteins, Hypersensitivity, Long-Term Potentiation, Male, Mice, Mice, Inbred Strains, Pain, Sarcosine | | |
|
|
|
|  Add to my archive |
Articles from other specialties: Cardiology, Allergy, Pediatric Surgery, Dermatology, Gynaecology - Obstetrics, Sports Medicine, Pathology, Ophtalmology, Nursing, Emergency Medicine, Rehabilitation, Vascular Surgery - Angiology |
