Imbalance between excitatory and inhibitory amino acids at spinal level is associated with maintenance of persistent pain-related behaviors.
Although the postsynaptic events responsible for development of pathological pain have been intensively studied, the relative contribution of presynaptic neurotransmitters to the whole process remains less elucidated. In the present investigation, we sought to measure temporal changes in spinal release of both excitatory amino acids (EAAs, glutamate and aspartate) and inhibitory amino acids (IAAs, glycine, ?-aminobutyric acid and taurine) in response to peripheral inflammatory pain state. The results showed that following peripheral chemical insult induced by subcutaneous bee venom (BV) injection, there was an initial, parallel increase in spinal release of both EAAs and IAAs, however, the balance between them was gradually disrupted when pain persisted longer, with EAAs remaining at higher level but IAAs at a level below the baseline. Moreover, the EAAs-IAAs imbalance at the spinal level was dependent upon the ongoing activity from the peripheral injury site. Intrathecal blockade of ionotropic (NMDA and non-NMDA) and metabotropic (mGluRI, II, III) glutamate receptors, respectively, resulted in a differential inhibition of BV-induced different types of pain (persistent nociception vs. hyperalgesia, or thermal vs. mechanical hyperalgesia), implicating that spinal antagonism of any specific glutamate receptor subtype fails to block all types of pain-related behaviors. This result provides a new line of evidence emphasizing an importance of restoration of EAAs-IAAs balance at the spinal level to prevent persistence or chronicity of pain.
Institute for Biomedical Sciences of Pain, Capital Medical University, Beijing 100069, PR China.
Lai-Hong
LH
Yan
Jun-Feng
JF
Hou
Ming-Gang
MG
Liu
Meng-Meng
MM
Li
Xiu-Yu
XY
Cui
Zhuo-Min
ZM
Lu
Fu-Kang
FK
Zhang
Yang-Yuan
YY
An
Lin
L
Shi
Jun
J
Chen
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001514:Bee Venoms; D001522:Behavior, Animal / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000378:metabolism; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000502:physiology; D013116:Spinal Cord / Q000378:metabolism*
D000596:Amino Acids; D001514:Bee Venoms; D018691:Excitatory Amino Acid Antagonists; D018846:Excitatory Amino Acids; D017470:Receptors, Glutamate