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.
journal_name
Anesthesiologyjournal_title
Anesthesiologyauthors
Tanabe M,Takasu K,Yamaguchi S,Kodama D,Ono Hdoi
10.1097/ALN.0b013e31816c9044subject
Has Abstractpub_date
2008-05-01 00:00:00pages
929-37issue
5eissn
0003-3022issn
1528-1175pii
00000542-200805000-00022journal_volume
108pub_type
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