Effects of GABA receptor antagonist on trigeminal caudalis nociceptive neurons in normal and neonatally capsaicin-treated rats

We have recently demonstrated that significant increases in cutaneous mecha noreceptive field (RF) size and spontaneous activity occur in nociceptive n eurons of trigeminal subnucleus caudalis (Vc, the medullary dorsal horn) of adult rats depleted of C-fiber afferents by neonatal treatment with capsai cin. These neuronal changes in capsaicin-treated (CAP) rats are suggestive of central neuroplasticity and involve N-methyl-D-aspartic acid (NMDA) rece ptor mechanisms. The present study examined whether the GABA(A) receptor an tagonist bicuculline (BIC) or the GABA(B) receptor antagonist 2-hydroxysacl ofen (SAC) can influence the RF properties and activity of Ve nociceptive n eurons classified as either nociceptive-specific or wide-dynamic range in C AP adult rats or in neonatally vehicle-treated (CON) rats. C-fiber depletio n was confirmed in the CAP rats by a significant decrease in plasma extrava sation of Evans blue dye in a skin area receiving topical application of mu stard oil, a small-fiber excitant and inflammatory irritant As previously r eported, marked increases in cutaneous RF size and spontaneous activity occ urred in Vc nociceptive neurons of adult CAP rats, compared with CON rats. GABA(A) receptor blockade by BIC (i.t.) in CON rats produced a significant increase in spontaneous activity and in pinch RF size and tactile RF size ( or appearance of a tactile area in the RF of nociceptive-specific neurons), as well as a significant lowering of the mechanical threshold and a signif icant enhancement of responses to pinch stimuli applied to the RF. In CAP r ats, GABA(B) receptor blockade also produced significant changes similar to those documented in CON rats, except for a paradoxical and significant dec rease in pinch RF size and no noticeable changes in responses to pinch stim uli. GABA(A) receptor blockade by SAC (i.t.) did not produce any significan t changes in Vc nociceptive neurons in either CON or CAP rats. These result s suggest that GABA(A) receptor-mediated inhibition may be involved in main taining the functional expression of Vc nociceptive neuronal properties in normal conditions, and that in animals depleted of their C-fiber afferents, some features of this GABA(A) receptor-mediated modulation may be disrupte d such that a GABA(A) receptor-mediated excitation is manifested.