Chronic pain produces psychologic distress, which often leads to mood disorders such as depression. Co-existing chronic pain and depression pose a serious socio-economic burden and result in disability affecting millions of individuals, which urges the development of treatment strategies targeting this comorbidity. Ketamine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, is shown to be efficient in treating both pain and depression-related symptoms. However, the molecular characteristics of its role in chronic pain-induced depression remain largely unexplored. Hence, we studied the behavioral and molecular effects of a single systemic administration of ketamine (15 mg/kg, i.p.) on mechanical hypersensitivity and depressive-like consequences of chronic neuropathic pain. We showed that ketamine transiently alleviated mechanical hypersensitivity (lasting <24 h), while its antidepressant effect was observed even 72 h after administration. In addition, ketamine normalized the upregulated expression of the mitogen activated protein kinase (MAPK) phosphatase 1 (MKP-1) and the downregulated phosphorylation of extracellular signal-regulated kinase (pERK) in the anterior cingulate cortex (ACC) of mice displaying...Continue Reading
MKP-1 (3CH134), an immediate early gene product, is a dual specificity phosphatase that dephosphorylates MAP kinase in vivo
The dual specificity mitogen-activated protein kinase phosphatase-1 and -2 are induced by the p42/p44MAPK cascade.
Mapping of punctuate hyperalgesia around a surgical incision demonstrates that ketamine is a powerful suppressor of central sensitization to pain following surgery
Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1
Modulation of formalin-induced behaviors and edema by local and systemic administration of dextromethorphan, memantine and ketamine
Functional anatomical correlates of antidepressant drug treatment assessed using PET measures of regional glucose metabolism
Cold allodynia and hyperalgesia in neuropathic pain: the effect of N-methyl-D-aspartate (NMDA) receptor antagonist ketamine--a double-blind, cross-over comparison with alfentanil and placebo
ERK1/2 achieves sustained activation by stimulating MAPK phosphatase-1 degradation via the ubiquitin-proteasome pathway.
Peripheral antihyperalgesic and analgesic actions of ketamine and amitriptyline in a model of mild thermal injury in the rat
Systemic ketamine inhibits hypersensitivity after surgery via descending inhibitory pathways in rats
N-methyl-D-aspartate receptor subtype mediated bidirectional control of p38 mitogen-activated protein kinase
Cooperation of ERK and SCFSkp2 for MKP-1 destruction provides a positive feedback regulation of proliferating signaling
Increases in the activated forms of ERK 1/2, p38 MAPK, and CREB are correlated with the expression of at-level mechanical allodynia following spinal cord injury
Low GABA concentrations in occipital cortex and anterior cingulate cortex in medication-free, recovered depressed patients
Activation of Erk in the anterior cingulate cortex during the induction and expression of chronic pain.
Mitogen-activated protein (MAP) kinase/MAP kinase phosphatase regulation: roles in cell growth, death, and cancer
Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction and expression of affective pain.
Pharmacological aspects and potential new clinical applications of ketamine: reevaluation of an old drug
Ketamine produces effective and long-term pain relief in patients with Complex Regional Pain Syndrome Type 1
Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: a double-blind placebo controlled study
Recommendations for the pharmacological management of neuropathic pain: an overview and literature update.
Inhibition of spinal astrocytic c-Jun N-terminal kinase (JNK) activation correlates with the analgesic effects of ketamine in neuropathic pain
Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure
Biphasic activation of extracellular signal-regulated kinase in anterior cingulate cortex distinctly regulates the development of pain-related anxiety and mechanical hypersensitivity in rats after incision
A single subanesthetic dose of ketamine relieves depression-like behaviors induced by neuropathic pain in rats.
Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents
Early molecular alterations in anterior cingulate cortex and hippocampus in a rodent model of neuropathic pain.
Comprehensive analysis of the lysine acetylome and succinylome in the hippocampus of gut microbiota-dysbiosis mice.
Efficacy of ketamine in relieving neuropathic pain: a systematic review and meta-analysis of animal studies.
Tianeptine induces expression of dual specificity phosphatases and evokes rebound emergence of cortical slow wave electrophysiological activity.
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