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To evaluate the possible relationship between sleep disturbances and primary headaches.
Learn More >Peripheral nerve injury can lead to remodeling of brain circuits, and this can cause chronification of pain. We have recently reported that male mice subjected to spared injury of the sciatic nerve undergo changes in the function of the medial prefrontal cortex (mPFC) that culminate in reduced output of layer 5 pyramidal cells. More recently, we have shown that this is mediated by alterations in synaptic inputs from the basolateral amygdala (BLA) into GABAergic interneurons in the mPFC. Optogenetic inhibition of these inputs reversed mechanical allodynia and thermal hyperalgesia in male mice. It is known that the processing of pain signals can exhibit marked sex differences. We therefore tested whether the dysregulation of BLA to mPFC signaling is equally altered in female mice. Injection of AAV-Arch3.0 constructs into the BLA followed by implantation of a fiberoptic cannula into the mPFC in sham and SNI operated female mice was carried out, and pain behavioral responses were measured in response to yellow light mediated activation of this inhibitory opsin. Our data reveal that Arch3.0 activation leads to a marked increase in paw withdrawal thresholds and latencies in response to mechanical and thermal stimuli, respectively. However, we did not observe nerve injury-induced changes in mPFC layer 5 pyramidal cell output in female mice. Hence, the observed light-induced analgesic effects may be due to compensation for dysregulated neuronal circuits downstream of the mPFC.
Learn More >The experience of pain relief arises from physiological and psychological factors, and attributes such as the commercial features of analgesic treatments have been shown to influence placebo analgesia by affecting treatment expectations. Therefore, treatment valuation from price information should influence the placebo analgesic effect. This hypothesis was tested in a functional magnetic resonance imaging (fMRI) study in which healthy subjects were enrolled in a two-day experiment. On day 1, the participants (n=19) had treatment experiences with two different placebo creams during a conditioning session without receiving information on treatment price. On day 2, placebo analgesia was tested after providing price information (high vs. low) while fMRI was performed. The results showed that the higher-priced placebo treatment lead to enhanced pain relief. Placebo analgesia in response to the higher priced treatment was associated with activity in the ventral striatum, ventromedial prefrontal cortex and ventral tegmental area. The behavioral results indicate that the experience of pain was influenced by treatment valuation from price. Our findings reveal that the context of values in pain control is associated with activity in expectation- and reward-related circuitry. Perspective: Treatment with higher price was associated with enhanced placebo analgesia, and this effect was influenced by activities in expectation and reward processing brain areas. The context of value such as medical cost influences cognitive evaluation processes to modulate pain. Our study may help evaluate a patient's preference toward high-priced drugs.
Learn More >While much of the literature provides positive support for psychological interventions for chronic pain, two recent meta-analyses indicate small to moderate benefits only. This inconsistency in findings suggests that there are other treatment-related variables to consider. One possible consideration pertains to treatment format, as psychological models form the basis for both unidisciplinary psychology and integrated interdisciplinary treatments for chronic pain. Therefore, a comparative meta-analysis of unidisciplinary and interdisciplinary treatments was performed to determine whether there were differences in treatment effect size (ES) at post-treatment and follow-ups of up to one year. One specific treatment model, Acceptance and Commitment Therapy (ACT), was investigated as it was felt that this literature was extensive enough to perform the planned analysis, while also being circumscribed enough in size to make it feasible. In total, 29 articles met inclusion criteria, 13 reported outcomes for unidisciplinary ACT and 15 for interdisciplinary ACT. At both post-treatment and follow-up, interdisciplinary ACT had a greater ES for physical disability, psychosocial impact and depression compared to unidisciplinary ACT. No differences in ES were observed for pain intensity, pain-related anxiety, or pain acceptance. Findings remained the same when study heterogeneity was considered. There was a significant difference observed between treatment format and treatment duration – on average, unidisciplinary interventions were of shorter duration than interdisciplinary interventions. Moderation analyses examining the relation between total treatment duration and ES generally indicated a moderate positive relation between treatment length and ES. This relation was strong for psychosocial impact. Perspective: A comparative meta-analysis examined the relative ES of unidisciplinary (i.e., clinical psychology only) and interdisciplinary ACT for chronic pain in 29 studies. The ES for interdisciplinary ACT was larger than unidisciplinary ACT for physical disability, psychosocial impact, and depression. No differences were present for pain intensity, anxiety, and acceptance.
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