Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0423716 (Neuropathic pain)
 1,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain is a chronic condition that is challenging to treat. It often produces considerable physical disability and emotional distress. Patients with neuropathic pain often experience depression and anxiety both of which are known to be temporally correlated with noradrenergic dysfunction in the locus coeruleus (LC) as pain becomes chronic. Antidepressants are the first-line drug therapy for neuropathic pain, and the LC represents a potential target for such therapy. In this study, we evaluated the efficacy of the tricyclic antidepressant desipramine (DMI, a noradrenaline reuptake inhibitor) in preventing or relieving the noradrenergic impairment induced by neuropathic pain. The treatment started before or after the onset of the anxiodepressive phenotype ("early or late treatment") in adult rats subjected to chronic sciatic constriction. Electrophysiological and western blotting assays showed LC dysfunction (increased bursting activity, alpha2-adrenoceptor sensitivity, tyrosine hydroxylase, and noradrenaline transporter expression) in chronic constriction injury at long term. These noradrenergic changes were concomitant to the progression of anxiety and despair-like features. Desipramine induced efficient analgesia, and it counteracted the despair-like behavior in chronic constriction injury-DMI animals, reducing the burst rate and tyrosine hydroxylase expression. Surprisingly, "early" DMI treatment did not modify pain-induced anxiety, and it dampened pain aversion, although these phenomena were abolished when the treatment commenced after noradrenaline impairment had been established. Hence, DMI seems to produce different outcomes depending when the treatment commences, indicating that the balance between the benefits and adverse effects of DMI therapy may shift as neuropathy progresses.
 ...
PMID:The onset of treatment with the antidepressant desipramine is critical for the emotional consequences of neuropathic pain. 3013 Mar 2

Neuropathic pain can be a predictor of severe emotional distress, up to full-blown depressive states. In these patients, it is important to move beyond the sole treatment of pain, to recognize depressive symptoms, and to ultimately improve the quality of life. We systematically searched for published and unpublished clinical trials assessing the efficacy and tolerability of antidepressants vs placebo on depression, anxiety and quality of life in patients with neuropathic pain, and pooled data in a meta-analysis. A total of 37 studies fulfilled eligibility criteria and 32 provided data for meta-analysis. Antidepressants were more effective than placebo in improving depressive symptoms (standardized mean difference -0.11; 95% confidence interval -0.20 to -0.02), although the magnitude of effect was small, with a number needed to treat of 24. No significant difference emerged between antidepressants and placebo in reducing anxiety. Quality of life seemed improved in patients on antidepressants, as did pain. Acceptability and tolerability were higher in patients on placebo. To the best of our knowledge, this is the first meta-analysis specifically focusing on the effect of antidepressants on psychiatric symptoms and quality of life in patients with neuropathic pain. Our findings suggest that despite their potential benefit in patients with neuropathic pain, antidepressants should be prescribed with particular care because they might be less tolerable in such a fragile population. However, our findings warrant further research to explore how a correct use of antidepressants can help patients to cope with the consequences of neuropathic pain on their psychosocial health and quality of life.
 ...
PMID:Beyond pain: can antidepressants improve depressive symptoms and quality of life in patients with neuropathic pain? A systematic review and meta-analysis. 3114 10

Pain and emotional distress have a reciprocal relation. The amygdala has been implicated in emotional processing. The central nucleus of the amygdala (CeA) receives nociceptive information from the dorsal horn of spinal cord and is responsible for the central plasticity in chronic pain. Neuropathic pain is a type of severe chronic pain and can be strongly influenced by emotional components. Plastic changes in the CeA may play a key role in the development or maintenance or both of neuropathic pain. We studied the expression levels of proteins in the CeA of spinal nerve transection (SNT) model rats. Total tissue lysate proteins were separated by two-dimensional-gel electrophoresis (2D-PAGE). Gels from different time points were compared using Progenesis SameSpot software, and the spots with Fold Change greater than 2 were excised for protein identification by mass spectrometry. We identified more than 50 cytosolic proteins as significantly altered in their expression levels in the CeA of SNT rats, and most of these changes have been validated at mRNA levels by qRT-PCR. We also identified more than 40 membrane proteins as notably up- or down-regulated in the CeA of SNT model rats relative to a control using stable isotope dimethyl labeling nano-LC-MS/MS based proteomics and found that one such protein, doublecortin (DCX), a microtubule-associated protein expressed by neuronal precursor cells during development, is specifically localized in the membrane fraction without changes in total amount of the protein. Immunohistochemistry showed that doublecortin is expressed in processes in the CeA of rats 7 and 21 days after SNT surgery, suggesting that doublecortin is one of the proteins that may contribute to the plastic changes, namely, redevelopment or rewiring of neural networks, in the CeA in the neuropathic pain model. These dysregulated proteins may play roles in reciprocal relationships between pain and psychological distress in the amygdala and contribute to central sensitization. Data are available via ProteomeXchange with identifier PXD017473.
 ...
PMID:Quantitative Proteomic Analysis of the Central Amygdala in Neuropathic Pain Model Rats. 3205 77