Periaqueductal gray matter glutamate and GABA decrease following subcutaneous formalin injection in rat

GLUTAMATE and GABA are important nociception modulating transmitters in spe cific brain regions, i.e. the spinal cord, the thalamic nuclei and the peri aque-ductal gray (PAG). However, quantitative and topographical changes in glutamate and GABA release in these brain regions during peripheral inflamm ation episodes have not been characterized in awake animals. To address thi s issue, an in vivo microdialysis study was carried out in freely moving ra ts in order to analyze PAG extracellular glutamate and GABA concentrations following unilateral formalin injection into the dorsal skin of the right h ind-paw. Both glutamate and GABA release decreased after the injection of f ormalin during phase I and phase II of hyperalgesia. Because naloxone preve nted the decrease of GABA and glutamate release induced by formalin, this s tudy shows that, in vivo, a nociceptive stimulation may activate opioidergi c fibres into the PAG. The increased release of endogenous opioids may, in turn, inhibit the activity of the GABAergic neurons (i.e. opioid disinhibit ion). Formalin injection also decreased extracellular glutamate concentrati on. However, we found that intra-PAG perfusion with tetrodotoxin only decre ased GABA, but not glutamate dialysate values. Although it should be reason able to speculate that opioids also inhibit glutamate fibres, further inves tigation is needed to clarify whether or not the dialysate glutamate we mea sured reflects change in the metabolism or neurotransmitter pool of this am ino acid. NeuroReport 10:1403-1407 (C) 1999 Lippincott Williams & Wilkins.