Affective dimensions of pain and region -specific involvement of nitric oxide in the development of empathic hyperalgesia

Abstract

Empathy for pain depends on the ability to feel, recognize, comprehend and share painful emotional conditions of others. In this study, we investigated the role of NO in a rat model of empathic pain. Pain was socially transferred from the sibling demonstrator (SD) who experienced five formalin injection to the naïve sibling observer (SO) through observation. SO rats received L-NAME (a nonspecific NO synthase inhibitor) or L-arginine (a precursor of NO) prior to observing the SD. Nociception, and concentrations of NO metabolites (NOx) in the serum, left and right hippocampus, prefrontal cortex, and cerebellum were evaluated. Nociceptive responses were significantly increased in the painobserving groups. NOx levels measured 24 h after the last pain observation using the Griess method, were indicative of NOx concentration decreases and increases in the left hippocampus and cerebellum, respectively. There was an increase in tissue concentration of NOx in cerebellum and prefrontal cortex in both pain and observer groups 7 days after the fifth formalin injection. Our results suggest that NO is involved in development of empathic hyperalgesia, and observation of sibling's pain can change NO metabolites in different brain regions in observer rats.

CFA‐treated mice induce hyperalgesia in healthy mice via an olfactory mechanism

“…However, while CFA-treated mice exhibited thermal hypersensitivity in Hargreaves test, neither "bystander" mice nor mice exposed to bedding from CFA-treated animals showed significant thermal hyperalgesia. Thermal hypersensitivity has been reported in bystanders using various thermal tests, such as tail immersion test, tail flick and hotplate tests Mohammadi, Kohlmeier, et al, 2020;Smith et al, 2016;Smith et al, 2021) In the present study, olfactory ablation using dichlobenil prevented CFA-bedding-induced nociceptive hypersensitivity. Dichlobenil damages the dorsomedial area of the main olfactory epithelium, an area that contains olfactory sensory neurons (Bergman et al, 2002;Mancuso et al, 1997;Vedin et al, 2004), but spares vomeronasal neurons (Denizet et al, 2017;John & Key, 2003;Piras et al, 2003).…”

“…However, while CFA‐treated mice exhibited thermal hypersensitivity in Hargreaves test, neither “bystander” mice nor mice exposed to bedding from CFA‐treated animals showed significant thermal hyperalgesia. Thermal hypersensitivity has been reported in bystanders using various thermal tests, such as tail immersion test, tail flick and hotplate tests (Mohammadi, Ahmadi‐Zeidabadi, et al., 2020; Mohammadi, Kohlmeier, et al., 2020; Smith et al., 2016; Smith et al., 2021), as well as Hargreaves test (Langford et al., 2006). In our study, the lack of thermal hyperalgesia in bystander mice using Hargreaves test could be a result of multiple factors, including social context during testing (e.g., dyads vs. individuals), the intensity of radiant heat stimulation, and other environmental factors that we may not understand fully.…”

Lysophosphatidic acid receptor type‐1 mediates brain activation in micro‐positron emission tomography analysis in a fibromyalgia‐like mouse model

“…Indeed, the present study showed that ICS caused an activation in cognition‐related brain regions, such as the LS, dHP, and vHP (Mokhtari et al, 2019; Sweeney & Yang, 2015). In addition to their cognitive functions, the septal nucleus and hippocampus are also involved in the modulation of affective pain (Favaroni Mendes & Menescal‐de‐Oliveira, 2008; Mohammadi et al, 2020). Several reports have demonstrated that chronic pain‐related central sensitization is associated with widespread alterations in the connectivity between the ACC and the striatum or dmStr (Spisak et al, 2017; Zhuang et al, 2021).…”

A novel animal model for understanding secondary traumatic stress and visceral pain in male rats

“…Observational paradigms for conditioned fear have shown that the behaviours of observer animals dramatically shift because of the fear experience, and indeed this effect can be exacerbated when the observers are familiar with the stimulus animal (Keum & Shin, 2016). Moreover, research suggests that the witnessing of pain experiences, such as formalin injections and models of neuropathic pain, induces significant changes in the behaviour of the observers (Baptista- de-Souza et al, 2015;Mohammadi et al, 2020). A more recent study from the same group has demonstrated that social pain transmission also induces alterations at the neural and hormonal level (Baptista-de-Souza et al, 2022).…”