Vagal, sympathetic and somatic sensory inputs to upper cervical (C1-C3) spinothalamic tract neurons in monkeys

Abstract

1. Myocardial ischemia activates vagal and sympathetic cardiac afferent fibers. The purpose of this study was to determine a neuro physiological basis for cardiac pain referred to C1-C3 somatic dermatomes. We hypothesized that afferent fibers traveling in vagal or sympathetic nerves transmit nociceptive information to C1-C3 spinothalamic tract (STT) neurons. 2. Electrical stimulation of the left stellate ganglion to excite cardiopulmonary sympathetic afferent fibers increased extracellular activity of 44 of 77 C1-C3 STT neurons examined in 33 anesthetized male monkeys (Macaca fascicularis); responses increased as stimulus strength increased. Additionally, this stimulus inhibited 5 cells, increased/decreased activity of 2 cells, and did not affect 26 cells. 3. Electrical stimulation of the left (ipsilateral) thoracic vagus nerve excited 41 of 78 C1-C3 STT neurons, inhibited 4 neurons, increased/decreased activity of 2 neurons, and did not affect 31 neurons. Responses increased with increasing stimulus strength Contralateral vagal stimulation excited 7 of 39 cells tested, inhibited 4 cells and did not affect 28 cells. 4. Effects of stimulating one or more vagal branches were examined on 22 C1-C3 STT neurons excited by input from left thoracic vagus nerve. Stimulation of the cardiac branch excited 11 of 16 cells tested; stimulation of the recurrent laryngeal nerve excited 11 of 18 cells; stimulation of vagal fibers just rostral to the diaphragm excited 8 of 19 cells. 5. Excitatory somatic receptive fields ranged from small ipsilateral fields to large, sometimes bilateral or noncontinuous fields. Many fields included the ipsilateral neck and/or inferior jaw. Thirty-nine of 74 neurons examined were wide dynamic range (WDR), 21 were high threshold (HT), 6 were low threshold (LT), and 8 did not respond to brushing or noxious pinching of somatic tissues. Most (38 of 39) WDR cells responded to stimulation of the stellate ganglion or vagal fibers, as did 18 of 21 HT cells, 3 of 6 LT cells, and 2 of 8 cells unresponsive to brush or pinch stimuli. 6. Results of this study supported the concept that vagal and/ or sympathetic afferent activation of C1-C3 STT neurons might provide a neural mechanism for referred pain that originates in the heart or other visceral organs but is perceived in the neck and jaw region. Additionally, C1-C3 STT neurons processed sensory information from widespread regions of the body.

c-Fos expression in rat brain stem and spinal cord in response to activation of cardiac ischemia-sensitive afferent neurons and electrostimulatory modulation

“…Second, the nonischemic afferent signaling, involving arterial baroreceptor procedures, did not cause any significant Fos expression at the cervical or thoracic level. Furthermore, the upper thoracic dorsal rhizotomy virtually eliminated Fos expression in the cervical and thoracic dorsal horns as well as in the NTS in response to either procedure, in agreement with previous evidence (8,13,22,23,25) that the majority of the sensory neurons responsive to cardiac ischemia are located in dorsal root ganglia between T 1 and T 6 . Although there is evidence that nodose ganglion cardiac afferent neurons also transmit ischemic signals, only ϳ10% of these neurons are sensitive to the mechanical and chemical stimuli associated with cardiac ischemia (2).…”

“…The cells demonstrating increased expression of Fos are found at the neuroaxis levels previously identified by electrophysiological studies as being activated in response to CISAN stimulation (8,13,17,21,23,30,37). To our knowledge, this is the first report to localize Fos-positive cells at different sites in the CNS depending on the method used to activate CISAN.…”

“…The majority are associated with spinal segments T 2 -T 6 , and their axons terminate mainly in laminae I, V, VII, and X (21). Although the majority of cardiac vagal afferent fibers activated by coronary artery occlusion (38) project directly to the nucleus tractus solitarius (NTS) (8), they also excite neurons in the spinothalamic tract (STT) in spinal segments C 1 -C 3 . Cardiac chemosensitive fibers transmit signals through the dorsal laminae and a number of spinoanterolateral ascending tracts, including the STT, primarily in spinal segments C 1 -C 3 and T 2 -T 6 , and then to a number of higher sites (13,15,23).…”

Left vagal stimulation induces dynorphin release and suppresses substance P release from the rat thoracic spinal cord during cardiac ischemia

“…For example, disruption of the circuitry in the C 1 -C 2 relay by the excitotoxin, ibotenic acid, eliminated the inhibition of vagal stimulation on thoracic spinal neurons (56). The results from these experiments (56) and others from Foreman's laboratory group (6,7,56) indicate that the inhibitory effects on thoracic neurons by vagal stimulation do not require direct descending pathways from supraspinal nuclei but rather that propriospinal nuclei in the upper cervical spinal cord are excited by vagal stimulation, and the excitation of this pathway accounts for a large part of the suppression of thoracic nuclei activity. Given these findings from Foreman's group and our laboratory, suppression of the irSP release, both at rest and during CoAO while LVS was applied, may also involve propriospinal pathways activated in the cervical segments.…”

Chest pain and angina pectoris – or the ugly swan and the beautiful duckling

“…This might provide a neural mechanism for referred pain that originates in the heart or other visceral organs but is perceived in the neck and jaw region. 5 Especially electrical stimulation of a cardiac branch of the left vagus nerve in humans can cause referred craniofacial pain. 6 Of interest is the lack of pain alarm in some patients, which of course leads to increased morbidity and mortality.…”