Anterior Cingulate Cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis (CP), but cortical modulation of painful CP remains elusive. Here, we examined the role of the anterior cingulate cortex (ACC) in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid (TNBS). TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in rats. Morphological data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii (NTS) and ACC, and some FOS-expressing neurons in the NTS projected to the ACC. In addition, a larger portion of ascending fibers from the NTS innervated pyramidal neurons, the neural subpopulation primarily expressing FOS under the condition of painful CP, rather than GABAergic neurons within the ACC. CP rats showed increased expression of vesicular glutamate transporter 1, and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor (NMDAR) subunit NR2B and the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) subunit GluR1 within the ACC. Microinjection of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats, which was similar to the analgesic effect of endomorphins injected into the ACC. Specifically inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety, whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP rats. Taken together, these findings provide neurocircuit, biochemical, and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats, as well as novel insights into the cortical modulation of painful CP, and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.

Pre-Clinical Study of Immediate Effects of Religious and Non-Religious Mindfulness Practice on Cardiovascular and Cortical Modulation

Although low levels of stress can be motivating, high levels of stress – especially when it is sustained – can be detrimental to mental and physical health. Mindfulness practice has been widely applied in health care worldwide as an effective stress management approach. This study compared the immediate effects of two types (religious: Serenity Prayer; and non-religious: Body Scan) of mindfulness practice with a control condition (resting: sitting) in six adults. This study found no statistically significant difference between the conditions, but data visualization showed a trend of cardiovascular modulation (increased high frequency of heart rate variability) and cortical modulation (increased alpha to beta ratio and theta to beta ratio of quantitative encephalogram) with a greater level of perceived stress-relieved by both types of mindfulness practice. In addition, religious belief may be a moderator of the effects of intervention. The results of this study offered insight into the effect of prayer on cardiovascular and cortical modulation for promoting the wellbeing of a person.

Investigating the Effects of tDCS on Visual Orientation Discrimination Task Performance: “the Possible Influence of Placebo”

The non-invasive neuromodulation technique tDCS offers the promise of a low-cost tool for both research and clinical applications in psychology, psychiatry, and neuroscience. However, findings regarding its efficacy are often equivocal. A key issue is that the clinical and cognitive applications studied are often complex and thus effects of tDCS are difficult to predict given its known effects on the basic underlying neurophysiology, namely alterations in cortical inhibition-excitation balance. As such, it may be beneficial to assess the effects of tDCS in tasks whose performance has a clear link to cortical inhibition-excitation balance such as the visual orientation discrimination task (ODT). In prior studies in our laboratory, no practice effects were found during 2 consecutive runs of the ODT, thus in the current investigation, to examine the effects of tDCS, subjects received 10 min of 2 mA occipital tDCS (sham, anode, cathode) between a first and second run of ODT. Surprisingly, subjects’ performance significantly improved in the second run of ODT compared to the first one regardless of the tDCS stimulation type they received (anodal, cathodal, or sham-tDCS). Possible causes for such an improvement could have been due to either a generic “placebo” effect of tDCS (as all subjects received some form of tDCS) or an increased delay period between the two runs of ODT of the current study compared to our previous work (10-min duration required to administer tDCS as opposed to ~ 2 min in previous studies as a “break”). As such, we tested these two possibilities with a subsequent experiment in which subjects received 2-min or 10-min delay between the 2 runs (with no tDCS) or 10 min of sham-tDCS. Only sham-tDCS resulted in improved performance thus these data add to a growing literature suggesting that tDCS has powerful placebo effect that may occur even in the absence of active cortical modulation.