Distribution and properties of visceral nociceptive neurons in rabbit cingulate cortex

Abstract

Human imaging localizes most visceral nociceptive responses to anterior cingulate cortex (ACC), however, imaging in conscious subjects cannot completely control anticipatory and reflexive activity or resolve neuron activity. This study overcame these shortcomings by recording individual neuron responses in 12 anesthetized and paralyzed rabbits to define the visceronociceptive response pattern by region and layer. Balloon distension was applied to the colon at innocuous (15 mmHg) or noxious (60 mmHg) intensities, and innocuous and noxious mechanical, thermal and electrical stimuli were applied to the skin. Simultaneous recording from multiple regions assured differences were not due to anesthesia and neuron responses were resolved by spike sorting using principal components analysis. Of the total 346 neurons, 48% were nociceptive; responding to noxious levels of visceral or cutaneous stimulation, or both. Visceronociceptive neurons were most frequent in ACC (39%) and midcingulate cortex (MCC, 36%) and infrequent in retrosplenial cortex (RSC, 12%). In contrast, cutaneous nociceptive units were higher in MCC (MCC, 43%; ACC, 32%; RSC, 23%). Visceralspecific neurons were proportionately more frequent in ACC (37%), while cutaneous-specific units predominated in RSC (62.5%). Visceral nociceptive response durations were longer than those for cutaneous responses. Postmortem analysis of electrode tracks confirmed regional designations, and laminar analysis found inhibitory responses mainly in superficial layers and excitatory in deep layers. Thus, cingulate visceral nociception extends beyond ACC, this is the first report of nociceptive activity in RSC including nociceptive cutaneous responses, and these regional differences require a new model of cingulate nociceptive processing.

Effect of electroacupuncture on P2X3 receptor regulation in the peripheral and central nervous systems of rats with visceral pain caused by irritable bowel syndrome

“…In recent years, the neuroimaging of humans showed that in patients with IBS, the functional activity of the brain plays an important role in the response to visceral stimulation and reflects the severity of the IBS symptoms. As an important center of pain, the anterior cingulate cortex has extensive fiber links with the medial thalamus medulla, amygdala, periaqueductal gray matter, caudate nucleus, and other nuclei involved in the modulation of pain sensation [38][39][40]. Positron emission tomography (PET) showed that the cingulate cortex in patients with IBS was activated after CRD [41].…”

Cerebral cortex modulation of pain

“…These results suggest that the medial thalamic nucleus is the major thalamic relay that transmits nociceptive information to the ACC. Both visceral-and cutaneous-specific nociceptive neurons have also frequently been found in the ACC of rabbit, suggesting that the ACC is associated with both visceral and somatic pain [25] . Electrical stimulation of ACC can facilitate the paw withdrawal and tail-flick reflexes induced by noxious heating.…”

Cingulate Cortex and Pain Architecture

“…The highest density of cingulate nociceptive neurons is in ACC and they are activated by visceral and cutaneous stimuli (Gao et al, 2006;Sikes et al, 2008) including noxious colorectal distension in unrestrained rats (Wang et al, 2008). When MCC is analyzed, it too has nociceptive responses during noxious cutaneous and colorectal distension (Sikes et al, 2008) and in a pancreatitis model .…”

“…When MCC is analyzed, it too has nociceptive responses during noxious cutaneous and colorectal distension (Sikes et al, 2008) and in a pancreatitis model . Finally, nociception is not limited to ACC and MCC but includes adjacent M2 neurons.…”