SYNAPTIC MEDIATION FROM CUTANEOUS MECHANICAL NOCICEPTORS

1. Responses of dorsal horn neurons to cutaneous mechanical stimulatio n were studied in an in vitro preparation of hamster spinal cord with partially intact innervation from an isolated patch of hairy skin. Sta ble extracellular and intracellular recordings were obtained from cell s with different mechanoreceptive properties similar to those reported for other species in vivo. Analyses were made of the intracellular re sponses of 25 dorsal horn neurons activated selectively by mechanical stimulation to the skin patch. 2. Bath application of the broad spectr um, excitatory amino acid (EAA) receptor antagonist, kynurenic acid (1 mM) blocked excitation of 7 of 8 high-threshold mechanoreceptive unit s by either cutaneous nerve volleys or mechanical stimulation of the s kin. This concentration of kynurenic acid suppressed peripherally evok ed responses in 8 of 14 neurons responsive to innocuous mechanical sti muli. 3. High-threshold mechanoreceptive neurons of the superficial do rsal horn exhibited one of three distinctive patterns of postsynaptic potentials in response to electrical stimulation of cutaneous afferent fibers: 1) a simple fast excitatory postsynaptic potential (EPSP), 2) a fast EPSP with a prolonged decay phase lasting between 100 and 1,00 0 ms, and 3) a multiphasic response dissociable on the basis of stimul us strength consisting of a fast EPSP followed by a hyperpolarizing in hibitory postsynaptic potential (IPSP) (duration 80-100 ms). Gentle me chanical stimuli initiated inhibition from areas adjacent to the high- threshold mechanically excitatory field; this suggests that membrane h yperpolarization in these neurons was evoked by input from tow-thresho ld mechanoreceptors. 4. Bath application of 6-cyano-7-nitroquinoxaline -2,3-dione (CNQX, 10 mu M), a competitive EAA antagonist selective for non-N-methyl-D-aspartate (non-NMDA) receptor subtypes, substantially or completely (56-100%) suppressed EPSPs evoked from cutaneous afferen t fibers in high-threshold mechanoreceptive neurons. CNQX also decreas ed the membrane depolarization, the frequency of EPSPs, and the freque ncy of action potentials evoked by mechanical stimulation of the recep tive field. 5. CNQX (10 mu M) or kynurenic acid (1 mM) had considerabl y weaker effects on IPSPs than on EPSPs evoked from the periphery in s uperficial dorsal horn neurons. IPSP amplitudes were unchanged by thes e agents in some neurons and decreased by only 20-25% in others. 6. We conclude that L-glutamate acting on non-NMDA receptors mediates fast synaptic excitation of superficial dorsal horn neurons from peripheral mechanical nociceptors with myelinated fibers. Furthermore, the obser vations imply either an agent other than L-glutamate or one acting at different membrane receptors is a synaptic mediator for other peripher al afferent units including some activated by innocuous mechanical sti muli.