Brain pathways of pain empathy activated by pained facial expressions: a meta-analysis of fMRI using the activation likelihood estimation method

OBJECTIVE: The objective of this study is to summarize and analyze the brain signal patterns of empathy for pain caused by facial expressions of pain utilizing activation likelihood estimation, a meta-analysis method. DATA SOURCES: Studies concerning the brain mechanism were searched from the Science Citation Index, Science Direct, PubMed, DeepDyve, Cochrane Library, SinoMed, Wanfang, VIP, China National Knowledge Infrastructure, and other databases, such as SpringerLink, AMA, Science Online, Wiley Online, were collected. A time limitation of up to 13 December 2016 was applied to this study. DATA SELECTION: Studies presenting with all of the following criteria were considered for study inclusion: Use of functional magnetic resonance imaging, neutral and pained facial expression stimuli, involvement of adult healthy human participants over 18 years of age, whose empathy ability showed no difference from the healthy adult, a painless basic state, results presented in Talairach or Montreal Neurological Institute coordinates, multiple studies by the same team as long as they used different raw data. OUTCOME MEASURES: Activation likelihood estimation was used to calculate the combined main activated brain regions under the stimulation of pained facial expression. RESULTS: Eight studies were included, containing 178 subjects. Meta-analysis results suggested that the anterior cingulate cortex(BA32), anterior central gyrus(BA44), fusiform gyrus, and insula(BA13) were activated positively as major brain areas under the stimulation of pained facial expression. CONCLUSION: Our study shows that pained facial expression alone, without viewing of painful stimuli, activated brain regions related to pain empathy, further contributing to revealing the brain's mechanisms of pain empathy.

Ethanol Increases Mechanical Pain Sensitivity in Rats via Activation of GABA_A Receptors in Medial Prefrontal Cortex

Ethanol is widely known for its ability to cause dramatic changes in emotion, social cognition, and behavior following systemic administration in humans.Human neuroimaging studies suggest that alcohol dependence and chronic pain may share common mechanisms through amygdala-medial prefrontal cortex（m PFC） interactions. However, whether acute administration of ethanol in the m PFC can modulate pain perception is unknown.Here we showed that bilateral microinjections of ethanol into the prelimbic and infralimbic areas of the m PFC lowered the bilateral mechanical pain threshold for 48 h without influencing thermal pain sensitivity in adult rats.However, bilateral microinjections of artificial cerebrospinal fluid into the m PFC or bilateral microinjections of ethanol into the dorsolateral PFC（also termed as motor cortex area 1 in Paxinos and Watson＇s atlas of The Rat Brain. Elsevier Academic Press, Amsterdam, 2005） failed to do so, suggesting regional selectivity of the effects of ethanol. Moreover, bilateral microinjections of ethanol didnot change the expression of either pro-apoptotic（caspase-3 and Bax） or anti-apoptotic（Bcl-2） proteins, suggesting that the dose was safe and validating the method used in the current study. To determine whether c-aminobutyric acid A（GABA_A） receptors are involved in mediating the ethanol effects, muscimol, a selective GABA_Areceptor agonist, or bicuculline, a selective GABA_A receptor antagonist, was administered alone or co-administered with ethanol through the same route into the bilateral m PFC. The results showed that muscimol mimicked the effects of ethanol while bicuculline completely reversed the effects of ethanol and muscimol. In conclusion, ethanol increases mechanical pain sensitivity through activation of GABA_A receptors in the m PFC of rats.