Papers of the Week

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 Aδ- 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.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. Here we show that cervical and trigeminal afferents interact via presynaptic inhibition, where inputs to lamina I neurons undergo unidirectional as well as reciprocal control. The afferent-driven presynaptic inhibition shapes the trigeminocervical Aδ- and C-fiber input to lamina I neurons. This inhibition provides control of excitatory drive to lamina I neurons that regulates their convergent and cervical- or trigeminal-specific processing modes. Disruption of this control may contribute to development of primary headache syndromes.