Dopamine receptors in the anterior insular cortex modulate long‐term nociception in the rat

Abstract

The rostral agranular insular cortex (RAIC) receives dopaminergic projections from the mesolimbic system, which has been involved in the modulation of nociceptive processes. In this study we determined the contribution of dopamine D(1) and D(2) receptors in the RAIC regarding nociception processing in a neuropathic pain model, as well as inflammatory articular nociception measured as pain-induced functional impairment in the rat (PIFIR). Microinjection of vehicle or substances into the RAIC was performed after the induction of nociception. The groups were treated with: a dopamine D(1) receptor antagonist (SCH-23390), a dopamine D(1) receptor agonist (SKF-38393), a dopamine D(2) receptor agonist (TNPA) and a dopamine D(2) receptor antagonist (spiperone). Chronic nociception, induced by denervation, was measured by the autotomy score in which onset and incidence were also determined. The SCH-23390 and TNPA groups showed a decrease in the autotomy score and a delay on the onset as compared to control, whereas the PIFIR groups did not show statistical differences. This work shows the differential role of dopamine receptors within the RAIC in which the activation of D(2) or the blockade of D(1) receptors elicit antinociception.

Subthalamic deep brain stimulation modulates small fiber–dependent sensory thresholds in Parkinson’s disease

“…In the present study, we found that changes in WDT and HPT correlated to motor improvement when the stimulator was turned on. Experimental studies showed that dopaminergic pathways are implicated in pain integration and modulation to heat noxious stimulation [5,32,40]. Genetic factors also support the association between low dopaminergic activity and high pain sensitivity [35].…”

Cerebral cortex modulation of pain

“…Furthermore, application of dopamine reuptake inhibitor GBR-12935 in the RAIC produced antinociceptive effects [53] . The effect of dopamine is mediated by different receptors; ie, the activation of D (2) and the blockade of D(1) receptors elicit antinociception, since the dopamine D(1) receptor antagonist SCH-23390 and dopamine D(2) receptor agonist TNPA caused decreases in the autotomy score and a delay in the onset in the neuropathic pain model induced by denervation [54] . The RAIC has a higher density of dopamine fibers that arise principally from the ipsilateral ventral tegmental area/substantia nigra and from a set of neurons different from those that project to the medial prefrontal cortex [13] .…”

“…These cortical structures constitute, respectively, the medial and lateral pain systems, the nucleus submedius (Sm)-VLO-periaqueductal gray (PAG) system and the motor cortex system [3][4][5][7][8][9][10][11] . Multiple neurotransmitters, including opioid, glutamate, GABA and dopamine transmitters, are involved in the modulation of pain by these cortical structures [11][12][13][14][15] . This paper reviews recent studies on pain modulation by the aforementioned cerebral cortex structures in animals and human.…”

Does the salience network play a cardinal role in psychosis? An emerging hypothesis of insular dysfunction

“…Nonetheless, various sources of evidence suggest that a dopaminergic abnormality is likely to be associated with salience network dysfunction in individuals with schizophrenia. Dopamine has emerged as the primary neurochemical medi ator in relation to various traits and behaviours mediated by the insula (e.g., novelty-seeking, 140 craving, 141,142 nociception 143 ). Moreover, various studies have demonstrated the importance of dopaminergic modulation on the ACC during executive tasks, 144 suggesting that DA plays an important role in the function of the salience network.…”