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Pain. 2015 Oct;156(10):2042-51. doi: 10.1097/j.pain.0000000000000267.

Monosynaptic convergence of somatic and visceral C-fiber afferents on projection and local circuit neurons in lamina I: a substrate for referred pain.

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aInstituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal bNeuronal Networks, Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, Porto, Portugal cLaboratório de Biologia Experimental, Faculdade de Medicina, Universidade do Porto, Porto, Portugal dMTA-DE-NAP B-Pain Control Research Group, University of Debrecen, Debrecen, Hungary eDepartment of Physiology, University of Debrecen, Debrecen, Hungary.


Referred pain is a phenomenon of feeling pain at a site other than the site of the painful stimulus origin. It arises from a pathological mixing of nociceptive processing pathways for visceral and somatic inputs. Despite numerous studies based on unit recordings from spinal and supraspinal neurons, the exact mechanism and site of this mixing within the central nervous system are not known. Here, we selectively recorded from lamina I neurons, using a visually guided patch-clamp technique, in thoracic spinal cord preparation with preserved intercostal (somatic) and splanchnic (visceral) nerves. We show that somatic and visceral C fibers converge monosynaptically onto a group of lamina I neurons, which includes both projection and local circuit neurons. Other groups of lamina I neurons received inputs from either somatic or visceral afferents. We have also identified a population of lamina I local circuit neurons showing overall inhibitory responses upon stimulation of both nerves. Thus, the present data allow us to draw two major conclusions. First, lamina I of the spinal cord is the first site in the central nervous system where somatic and visceral pathways directly converge onto individual projection and local circuit neurons. Second, the mechanism of somatovisceral convergence is complex and based on functional integration of monosynaptic and polysynaptic excitatory as well as inhibitory inputs in specific groups of neurons. This complex pattern of convergence provides a substrate for alterations in the balance between visceral and somatic inputs causing referred pain.

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