Anterior Cingulate Cortex Contributes to Alcohol Withdrawal- Induced and Socially Transferred Hyperalgesia

Abstract

Pain is often described as a “biopsychosocial” process, yet social influences on pain and underlying neural mechanisms are only now receiving significant experimental attention. Expression of pain by one individual can be communicated to nearby individuals by auditory, visual, and olfactory cues. Conversely, the perception of another’s pain can lead to physiological and behavioral changes in the observer, which can include induction of hyperalgesia in “bystanders” exposed to “primary” conspecifics in which hyperalgesia has been induced directly. The current studies were designed to investigate the neural mechanisms responsible for the social transfer of hyperalgesia in bystander mice housed and tested with primary mice in which hyperalgesia was induced using withdrawal (WD) from voluntary alcohol consumption. Male C57BL/6J mice undergoing WD from a two-bottle choice voluntary alcohol-drinking procedure served as the primary mice. Mice housed in the same room served as bystanders. Naïve, water-drinking controls were housed in a separate room. Immunohistochemical mapping identified significantly enhanced Fos immunoreactivity (Fos-ir) in the anterior cingulate cortex (ACC) and insula (INS) of bystander mice compared to naïve controls, and in the dorsal medial hypothalamus (DMH) of primary mice. Chemogenetic inactivation of the ACC but not primary somatosensory cortex reversed the expression of hyperalgesia in both primary and bystander mice. These studies point to an overlapping neural substrate for expression of socially transferred hyperalgesia and that expressed during alcohol WD.

Validating Rat Model of Empathy for Pain: Effects of Pain Expressions in Social Partners

“…Moreover, a period of at least 24 h exposure to the bedding from hyperalgesic mice was shown to be essential for social transfer of pain hypersensitivity to other bystander mice (Smith et al, 2016 ). Although the olfactory cue-based transfer of pain hypersensitivity may not be empathic response as seen in our and other studies (for review see Chen, 2018 ), it would be of particular interest to see what is going to happen at the neural circuit level and the molecular/cellular levels in the brain between the two different models because both types of contagious pain involve the mPFC (Li et al, 2014 ; Smith et al, 2017 ). Based upon the results of previous and our present studies, we propose that the visual information be more critical for induction of empathy for pain or distress at the first sight or short duration of social communication, while other sensory information such as olfactory, auditory, and somatic sources should also be necessary when salient visual information is lacking.…”

The use of chemogenetic approaches in alcohol use disorder research and treatment

“…To date, several DREADDs have been successfully employed in AUD-related research studies (Table 1); these included investigations of binge or excessive alcohol intake (Cassataro et al, 2014;Cheng et al, 2017;den Hartog et al, 2016;Li et al, 2017;Navarro et al, 2016;Pleil et al, 2015), alcohol-seeking behavior (Bull et al, 2014;Cheng et al, 2017;Jaramillo et al, 2018;Pina & Cunningham, 2017;Pina, Young, Ryabinin, & Cunningham, 2015;Prasad & McNally, 2016), alcohol sensitization (Jaramillo et al, 2017), alcohol-induced reinstatement and extinction (Marchant et al, 2016;Prasad & McNally, 2016), as well as alcohol-induced anxiety (Kang et al, 2017), hyperalgesia (Smith, Walcott, Heinricher, & Ryabinin, 2017), and over-eating (Cains, Blomeley, Kollo, Racz, & Burdakov, 2017).…”

Alcohol and Pain: A Translational Review of Preclinical and Clinical Findings to Inform Future Treatment Strategies

“…Indeed, the social transfer of hyperalgesia may represent an adaptive biobehavioral process to facilitate the communication of dangers within a group of animals. Interestingly, chemogenetic inactivation of the ACC reduced hyperalgesia symptoms in both alcohol‐exposed mice and their bystander partners (Smith et al, ). These recent insights demonstrate the preclinical potential to investigate important social components of affective pain that may directly relate to the fundamental reinforcing properties of alcohol in human populations.…”