Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal.
Neuronal Networks Group, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto 4200-135, Portugal.
J Neurosci. 2022 Apr 27;42(17):3587-3598. doi: 10.1523/JNEUROSCI.0025-22.2022. Epub 2022 Mar 22.
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-fiber and C-fiber input reaches Lamina I projection neurons (PNs) and local-circuit neurons (LCNs). We propose that this inhibition provides a feedforward control of excitatory drive to Lamina I neurons that regulates their convergent and cervical-specific 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-fiber 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-specific or trigeminal-specific processing modes. Disruption of this control may contribute to development of primary headache syndromes.
颈部和三叉神经传入纤维支配相邻的颅区，它们在上颈段背角神经元上的会聚为原发性头痛综合征中的疼痛牵涉提供了潜在的基础。I 层神经元是这种机制的核心，因为它们将会聚的伤害性传入信息传递到脊髓上的疼痛中心。不幸的是，人们对供应 I 层神经元的三叉神经和颈神经传入之间的相互作用知之甚少。在这里，我们使用了雌雄大鼠，结果表明，颈神经和三叉神经传入通过突触前抑制相互作用，其中 I 层神经元的单突触传入经历单向和相互的突触前控制。这意味着传入驱动的突触前抑制塑造了三叉神经和颈 Aδ 纤维和 C 纤维传入到达 I 层投射神经元 (PNs) 和局部回路神经元 (LCNs) 的方式。我们提出，这种抑制为到达 I 层神经元的兴奋性驱动提供了前馈控制，从而调节它们的会聚和颈特异性或三叉神经特异性处理模式。因此，三叉神经和颈传入驱动的突触前抑制的破坏可能导致原发性头痛综合征的发展。
