Neural Mechanisms That Underlie Angina-Induced Referred Pain in the Trigeminal Nerve Territory: A c-Fos Study in Rats

The present study was designed to determine whether the trigeminal sensory nuclear complex (TSNC) is involved in angina-induced referred pain in the trigeminal nerve territory and to identify the peripheral nerve conducting nociceptive signals that are input into the TSNC. Following application of the pain producing substance (PPS) infusion, the number of Fos-labeled cells increased significantly in the subnucleus caudalis (Sp5C) compared with other nuclei in the TSNC. The Fos-labeled cells in the Sp5C disappeared when the left and right cervical vagus nerves were sectioned. Lesion of the C1-C2 spinal segments did not reduce the number of Fos-labeled cells. These results suggest that the nociceptive signals that conduct vagal afferent fibers from the cardiac region are input into the Sp5C and then projected to the thalamus. 1. Introduction Angina pectoris has been recognized as the cause of a variety of cardiac symptoms, including chest pain and pain that may radiate either to arm or to the neck and jaw. Foreman and colleagues anesthetized a primate and recorded the responses from the spinothalamic tract (STT) cells in the T1–T5 and C5-C6 segments of the animal’s spinal cord following either occlusion of the coronary artery or the injection of algesic chemicals into the pericardial sac. The authors also found a convergence of visceral and somatic input to the chest and upper arm [1]. Their findings were consistent with the observation that referred pain associated with an attack of angina pectoris commonly occurs in proximal somatic fields. The referred pain is explained by the convergence of visceral and somatic inputs to the same dorsal horn neuron in the nociceptive ascending pathway [2]. It is well known that angina pectoris induces toothache or neck and jaw pain. The dental literature has described the presence of toothaches attributed to angina attacks and coronary artery disease [3]. Thus, referral to the somatic structures in the territory of the trigeminal nerve is one of the characteristics of anginal pain, and the neural mechanisms of this pain are of particular interest because such mechanisms appear to be due to a convergence of trigeminal and spinal inputs in either the spinal cord or the trigeminal sensory nucleus. Several lines of electrophysiological studies have demonstrated that an injection of algesic chemicals into the pericardial sac results in increased activity in C1-C2 STT cells [4–7]. This finding suggests that angina-induced referred pain in the trigeminal nerve territory is attributed to the convergence of both inputs from