Presynaptic interactions between trigeminal and cervical nociceptive afferents supplying upper cervical lamina I neurons

Cervical and trigeminal afferents innervate neighboring cranial territories, and their convergence on upper cervical dorsal horn neurons provides a potential substrate for pain referral in primary headache syndromes Lamina I neurons are central to this mechanism as they relay convergent nociceptive input to supraspinal pain centers. Unfortunately, little is known about the interactions between trigeminal and cervical afferents supplying lamina I neurons. Here we used rats of both sexes to show that cervical and trigeminal afferents interact via presynaptic inhibition, where monosynaptic inputs to lamina I neurons undergo unidirectional as well as reciprocal presynaptic control. This means that afferent-driven presynaptic inhibition shapes the way trigeminal and cervical A delta- and C-fiber input reaches lamina I projection and local-circuit neurons. We propose that this inhibition provides a feedforward control of excitatory drive to lamina I neurons that regulates their convergent and cervical- or trigeminal-specific processing modes. As a consequence, disruption of the trigeminal and cervical afferent-driven presynaptic inhibition may contribute to development of primary headache syndromes.