Chronic Inflammatory Pain Alters Expression of Limbic MAPK Phosphatases.
Dakota Nerland, Allison Ash, Adam Garman, Jeffery Foltz, Gabriel Berenbeim, Benjamin Wilke, Lori Winter, Daniel T Christian, Vanja Duric
Chronic pain & management 2024 DOI: 10.29011/2576-957x.100055 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Male and female rats |
| Intervention | Ketamine |
| Dose | 10 mg/kg |
| Duration | 21-day pain paradigm |
| Topics | Depression |
| Keywords | Limbic Mkp-1 Mkp-2 Mkp-3 Chronic pain Sex differences Ketamine therapy |
| Citations | 1 |
| Key findings | Chronic pain activates MKP-1 and other DUSP genes in limbic brain regions in a sex- and region-specific manner, and ketamine blocks pain-induced upregulation of MKP-1. |
Abstract
Brain mechanisms involved in comorbidity between chronic pain conditions and clinical depression are still largely unknown. Our previous studies demonstrated that expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) is both necessary and sufficient for the development of enhanced behavioral emotionality (i.e., depressive- like behaviors) in rodents. Here, we investigated the role of the dual specificity phosphatase (DUSP) gene family, specifically MKP-1, MKP-2 and MKP-3, in limbic brain areas involved in affective pain processing and stress responses. Male rats exposed to 21 days of peripheral inflammatory pain exhibited a robust increase in MKP-1 gene expression within the hippocampus, prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Similar upregulation of hippocampal MKP-1 was also observed in female animals exposed to the same 21-day paradigm. However, the overall pattern of MKP-1 expression across various limbic areas differed in females exposed to chronic pain, as significant downregulation of MKP-1 was observed in the ACC, while no changes were detected within the PFC. Furthermore, similar limbic region-specific variances in pain-related dysregulation were also observed for MKP-2 and MKP-3. Finally, pain-induced upregulation of limbic MKP-1 was blocked by low-dose ketamine treatment (10 mg/kg) previously shown to produce rapid antidepressant effects in rodents. Overall, the results of this study suggest that chronic pain activates specific MKPs/DUSPs within limbic brain regions, which may underlie previously reported pain-related decreases in MAPK signaling. Thus, dysregulation of MKP-1 and other DUSP genes may play an important role in the development of mood disorders associated with chronic pain state.
Comparable studies
Other preclinical and animal studies on depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelics, but Not Ketamine, Produce Persistent Antidepressant-like Effects in a Rodent Experimental System for the Study of Depression Rats | 2020 | Preclinical study | |
| A Single Subanesthetic Dose of Ketamine Relieves Depression-like Behaviors Induced by Neuropathic Pain in Rats Rats with spared nerve injury (neuropathic pain model), sham-operated rats, and control... | 2011 | Animal experimental study | |
| Effects of N,N-Dimethyltryptamine on Rat Behaviors Relevant to Anxiety and Depression Adult male Sprague-Dawley rats | 2018 | Experimental study | |
| A non-hallucinogenic LSD analog with therapeutic potential for mood disorders. Mice and cultured rat cortical neurons | 2023 | Preclinical study | |
| Comparison of (R)-ketamine and lanicemine on depression-like phenotype and abnormal composition of gut microbiota in a social defeat stress model Susceptible mice after chronic social defeat stress | 2017 | Preclinical animal study |