The heptadecapeptide
histogranin, synthesized by adrenal chromaffin cells, is implicated in the
analgesia produced by transplanting chromaffin cells into the spinal cord, including block of
hyperalgesia mediated by
NMDA-subtype
glutamate receptors. To examine the neurophysiological basis for this
analgesia, we applied the stable analog [Ser(1)]-
histogranin (SHG) by iontophoresis near extracellularly recorded wide-dynamic range (WDR) neurons in anesthetized rats. When SHG was applied during peripheral electrical stimulation of A and C fibers at 0.1Hz, the C-fiber response was significantly inhibited but the A-fiber response was unaffected. SHG also opposed the
NMDA-receptor-dependent post-tetanic facilitation (wind-up) of C-fiber responses produced by increasing the rate of peripheral afferent stimulation to 1Hz for 20s. To test whether block of
NMDA-subtype receptors could be wholly or partially responsible for this suppression, SHG was applied during sequential pulsed iontophoresis of three agonists targeting distinct excitatory
synaptic receptors:
NMDA,
kainate and
substance P. All three excitatory effects were reversed by SHG; this reversal outlasted the 10-30min observation period when higher SHG doses were applied (>60nA).
Histogranin therefore probably produces prolonged spinal
analgesia by opposing the basal and potentiating synaptic effects of C-fibers on dorsal horn neurons. Actions besides or in addition to
NMDA-receptor antagonism (e.g., agonism at inhibitory postsynaptic receptors or block of voltage-gated
cation channels on C-fibers) are implied by the diversity of excitatory transmitters opposed by SHG.