Scopolamine into the anterior cingulate cortex diminishes nociception in a neuropathic pain model in the rat: an interruption of ‘nociception‐related memory acquisition’?

Abstract

The cingulate cortex plays a key role in the affective component related to pain perception. This structure receives cholinergic projections and also plays a role in memory processing. Therefore, we propose that the cholinergic system in the anterior cingulate cortex is involved in the nociceptive memory process. We used scopolamine (10 microg in 0.25 mircrol/saline) microinjected into the anterior cingulate cortex, either before thermonociception followed by a sciatic denervation, between thermonociception and denervation or after both procedures (n=10 each). The vehicle group (saline solution 0.9%, n=14) was microinjected before thermonociception. Chronic nociception was measured by the autotomy score, which onset and incidence were also determined. Group scopolamine-thermonociception-denervation (STD) presented the lowest autotomy score as compared to vehicle and group thermonociception-denervation-scopolamine (TDS) (vehicle vs. STD, p=0.002, STD vs. TDS, p=0.001). Group thermonociception-scopolamine-denervation (TSD) showed a diminished autotomy score when compared to TDS (p=0.053). STD group showed a delay in the onset of AB as compared to the rest of the groups. Group TSD presented a significative delay (p=0.048) in AB onset when compared to group TDS. There were no differences in the incidence between groups. The results show that nociception-related memory processed in the anterior cingulate cortex is susceptible of being modified by the cholinergic transmission blockade. When scopolamine is microinjected prior to the nociceptive stimuli, nociception-related memory acquisition is prevented. The evidence obtained in this study shows the role of the anterior cingulate cortex in the acquisition of nociception-related memory.

Expression of muscarinic M1 and M2 receptors in the anterior cingulate cortex associated with neuropathic pain

“…The muscarinic cholinergic system projects to this structure (Gaykema et al, 1990) where the presence of muscarinic receptors has been shown (Levey et al, 1991;Tohyama, 1998). This result obtained in a structure related to the cognitive sphere (ACC) impaired nociceptive related memory acquisition, rather than muscarinic analgesia per se (Ortega-Legaspi et al, 2003), as seen with agonists in other structures. This result obtained in a structure related to the cognitive sphere (ACC) impaired nociceptive related memory acquisition, rather than muscarinic analgesia per se (Ortega-Legaspi et al, 2003), as seen with agonists in other structures.…”

“…Scopolamine (10 lg diluted in 250 nl of saline solution) was microinjected at a rate of 0.5 ll/min during 30 s. This dose was chosen based on two previous reports (Farr et al, 2000;Ortega-Legaspi et al, 2003). Scopolamine (10 lg diluted in 250 nl of saline solution) was microinjected at a rate of 0.5 ll/min during 30 s. This dose was chosen based on two previous reports (Farr et al, 2000;Ortega-Legaspi et al, 2003).…”

“…This model has proven to be an useful tool to study central mechanisms of neuropathic pain and was used in our previous study (Ortega-Legaspi et al, 2003), the results of which led us to further investigate the dynamics of muscarinic receptors expression. We separated the animals according to AS in order to evaluate the changes related to those animals according to the lesser and greatest pain as well as those with medium AS values.…”

Expression of the Dopaminergic D1 and D2 Receptors in the Anterior Cingulate Cortex in a Model of Neuropathic Pain

“…Interestingly enough, the sample of animals used in this study was random which still showed that a difference in the expression of a receptor has an impact in the degree of autotomy. Furthermore, while this behaviour is developed over time, the present study shows a snapshot of the average day (eight) in which a control animal reaches its AS mean [14,18,31]. …”

Cortical modulation of pain

“…Such results are supported by other studies showing that scopolamine, a cholinergic antagonist, injected into the ACC before nociceptive stimulus results in reduction of pain later on. Scopolamine after pain stimulus does not reduce pain score, so it seems that ACC is involved in the memory of pain [67]. Presently there is no evidence that activation of the descending inhibitory system is involved in the pain avoidance mechanism described above.…”