Pm. Dougherty et al., COMBINED APPLICATION OF EXCITATORY AMINO-ACIDS AND SUBSTANCE-P PRODUCES LONG-LASTING CHANGES IN RESPONSES OF PRIMATE SPINOTHALAMIC TRACT NEURONS, Brain research reviews, 18(2), 1993, pp. 227-246
Sensitization of dorsal horn neurons following injury may underlie the
generation of secondary hyperalgesia and so the chemical basis of sen
sitization is now receiving considerable attention. The present study
used microiontophoretic applications of excitatory amino acids (EAA's)
and substance P (SP) to test their roles in the sensitization of prim
ate spinothalamic tract (STT) neurons. Of 70 STT cells examined in lam
inae I-VI of the dorsal horn, 40 showed an increase in responses to on
e or more EAA's following their co-application with SP. The increased
responses were usually specific to either N-methyl-D-aspartate (NMDA)
or to the non-NMDA agonists, quisqualate (QUIS) or pha-amino-3-hydroxy
-5-methylisoxazole-4-proprionic acid (AMPA). The enhancement of EAA re
sponses was long-lasting ( > 15 min) in 18 cases, was accompanied by s
imilarly long-lasting increases in responses to mechanical stimulation
of the receptive field in 14 cases and was accompanied by an increase
in responses to either glutamate (Glu) or aspartate (Asp) in eleven c
ases. A global decrease in all EAA responses tested was produced in 26
other STT neurons. The inhibition, unlike the increases, was generali
zed to both NMDA and non-NMDA ligands, was long-lasting in only six ca
ses and was never accompanied by a change in the responses to mechanic
al stimuli. The excitatory and inhibitory effects of SP on the respons
es to NMDA were uniformly reversed by the NK-1 receptor selective anta
gonist, CP96345. In contrast, only the inhibitory effects of SP on the
responses to QUIS or AMPA were reversed by CP96345. The long-lasting
enhancement of EAA responses by SP may follow the combined synaptic re
lease of the natural ligands in vivo, resulting in the sensitization o
f dorsal horn neurons and secondary hyperalgesia. However, the reducti
ons in EAA responses produced by SP are problematic for this hypothesi
s and need further elucidation.