• Liliana L Luz, Elisabete C Fernandes, Fanni Dora, Nikolay V Lukoyanov, Peter Szucs, and Boris V Safronov.
• Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
• Pain. 2019 Nov 1; 160 (11): 2612-2623.

AbstractNociceptive trigeminal afferents innervating craniofacial area, eg, facial skin and cranial meninges, project to a broad region in the medullary and upper cervical dorsal horn designated as the trigeminocervical complex. Lamina I neurons in the trigeminocervical complex integrate and relay peripheral inputs, thus playing a key role in both cranial nociception and primary headache syndromes. Because of the technically challenging nature of recording, the long-range trigeminal afferent inputs to the medullary and cervical lamina I neurons were not intensively studied so far. Therefore, we have developed an ex vivo brainstem-cervical cord preparation with attached trigeminal nerve for the visually guided whole-cell recordings from the medullary and cervical lamina I neurons. Two-thirds of recorded neurons generated intrinsic rhythmic discharges. The stimulation of the trigeminal nerve produced a complex effect; it interrupted the rhythmic discharge for hundreds of milliseconds but, if the neuron was silenced by a hyperpolarizing current injection, could elicit a discharge. The monosynaptic inputs from the trigeminal Aδ, high-threshold Aδ, low-threshold C, and C afferents were recorded in the medullary neurons, as well as in the cervical neurons located in the segments C1 to C2 and, to a lesser degree, in C3 to C4. This pattern of supply was consistent with our labelling experiments showing extensive cervical projections of trigeminal afferents. Excitatory inputs were mediated, although not exclusively, through AMPA/kainate and NMDA receptors, whereas inhibitory inputs through both GABA and glycine receptors. In conclusion, the trigeminocervical lamina I neurons receive a complex pattern of long-range monosynaptic and polysynaptic inputs from a variety of the trigeminal nociceptive afferents.

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