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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropathic pain is a chronic pain that results from lesion or dysfunction of the nervous system. Depression and cognitive decline are often coupled to chronic pain, suggesting the involvement of cortical areas associated with higher cognitive functions. We investigated layer 2/3 pyramidal neurons in acute slices of the contralateral medial prefrontal cortex (mPFC) in the rat spared nerve injury (SNI) model of neuropathic pain and found morphological and functional differences between the mPFC of SNI and sham-operated animals. Basal, but not apical, dendrites of neurons from SNI rats are longer and have more branches than their counterparts in sham-operated animals; spine density is also selectively increased in basal dendrites of neurons from SNI rats; the morphological changes are accompanied by increased contribution to synaptic currents of the NMDA component. Interestingly, the NMDA/AMPA ratio of the synaptic current elicited in mPFC neurons by afferent fiber stimulation shows linear correlation with the rats' tactile threshold in the injured (but not in the contralateral) paw. Our results not only provide evidence that neuropathic pain leads to rearrangement of the mPFC, which may help defining the cellular basis for cognitive impairments associated with chronic pain, but also show pain-associated morphological changes in the cortex at single neuron level.
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PMID:Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain. 1917 85

Neuropathic pain is common in the palliative care population; unless adequately treated, the pain can lead to chronic anxiety, depression, and social impairment. Many treatments have been proposed for neuropathic pain; however, it remains underdiagnosed, under-treated, and often requires long-term therapy with risk of adverse effects. Memantine (Namenda), an N-Methyl, D-aspartate receptor inhibitor currently marketed for the treatment of dementia, has been proposed as a medication for the treatment of neuropathic pain for its mechanism, safety, lack of serious adverse effects, and relatively rapid onset of action. However, clinical trials have not been promising so far and its routine use in neuropathic pain is not currently recommended.
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PMID:Memantine (Namenda) for neuropathic pain. 1919 60

Glutamate is the most widely distributed and a major excitatory neurotransmitter in the CNS. It has been found to play a critical role in various physiological functions in which increased glutamate or its subsequent stimulation is thought to have a role in pathophysiological mechanism of various CNS diseases like epilepsy, stroke, depression and pain. Early attempts to develop glutamatergic antagonists failed in clinical studies due to nonselective or competitive antagonism and have a lot of safety issues like loss of cognitive functions, psychomimetic effect and sedation. Neuropathic pain can be described as pain associated with damage or permanent alteration of the peripheral or central nervous system. At present, there are very few effective therapies for neuropathic pain. The current approach includes targeting specific or alternate binding sites of glutamate receptors, resulting in reduced CNS liabilities. Targeting the glutamatergic system shows a better efficacy and fewer side effects, compared with classical drugs for the treatment of neuropathic pain. This review discusses the various targets on glutamatergic system, which includes the receptors, transporters and enzymes, for the treatment of neuropathic pain and their advantages over classical glutamatergic antagonists. The review also highlights the newer drugs in clinical trials for neuropathic pain.
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PMID:Current approaches with the glutamatergic system as targets in the treatment of neuropathic pain. 1953 98

Neuropathic pain is initiated or caused by a primary lesion or dysfunction in the central and/or peripheral nervous systems, including infection, trauma, metabolic abnormalities, and nerve compression, and is typically accompanied by hyperalgesia and allodynia. Neuropathic pain can be mild to excruciating, debilitating, difficult to manage, cause depression, decrease the quality of life, require extremity amputations, and has a variety of clinical symptoms. It effects up to 5% of the population, 70% of patients with advanced cancer and inflammatory pathologies, and 95% of patients with spinal cord injuries. The primary treatments of neuropathic pain are antidepressants, anticonvulsants, local anesthetic/topical agents, and opioids. The rapidly evolving symptom- and mechanism-based approaches to the treatment of neuropathic pain holds promise for improving the quality of life of patients with neuropathic pain. However, pharmacological treatment of the symptoms are difficult because of the limited understanding of the underlying causes of the pain, and the systemic levels of multiple side effects induced by various agents at an effective dose. Further, neuropathic pain is often refractory to conventional analgesic treatments, with most patients obtaining only partial relief with these agents, and with tolerability or side effects often limiting their use. Alternative treatments to pharmacology include peripheral or neuraxial nerve blockade, and implanted cortical or spinal cord stimulators. However, the great need remains for development of new and more effective approaches to reducing neuropathic pain. This review examines various approaches currently used for treatment of neuropathic pain and potential new and more effective approaches.
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PMID:Reducing and eliminating neuropathic pain. 1999 36

Neuropathic pain (NeP) is prevalent in patients with peripheral neuropathy (PN), regardless of etiology. We sought to compare the efficacy of the cannabinoid nabilone as either monotherapy or adjuvant therapy with a first-line medication for NeP, gabapentin, in a patient population with PN-NeP. Patients diagnosed with PN-NeP were permitted to initiate monotherapy (nabilone or gabapentin) or add one of these two medications (adjuvant therapy) to their existing NeP treatment regimen in a non-randomized open-label nature. Baseline data collected included a primary outcome (visual analog scores [VAS] of pain) and secondary outcomes (quality of life [EuroQol 5 Domains and Short-Form 36] assessments and assessments of sleep [Medical Outcomes Sleep Study Scale {MOSSS}], anxiety and depression [Hospital Anxiety and Depression Scale], and pain [Brief Pain Inventory]). Reassessment and modulation of dosing and/or medications occurred at 3- and 6-month intervals. Medication adverse effects and drug efficacy, as well as questionnaires, were assessed at 6 months. Matched analysis of variance testing was performed to compare 3- and 6-month scores with baseline, as well as to compare therapies at equal time points. Significant improvements in pain VAS were seen in all treatment groups at 6 months. Numerous sleep parameters within MOSSS, Brief Pain Inventory, and Short-Form 36 improved in patients receiving nabilone or gabapentin either as monotherapy or adjuvant treatment. Hospital Anxiety and Depression Scale-A scores were significantly improved in all treatment groups. Sleep adequacy and the sleep problems index within the MOSSS improved in nabilone monotherapy patients in particular. The benefits of monotherapy or adjuvant therapy with nabilone appear comparable to gabapentin for management of NeP. We advocate for head-to-head randomized, double-blind studies for current therapies for NeP in order to determine potential advantages beneficial in this patient population.
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PMID:An open-label comparison of nabilone and gabapentin as adjuvant therapy or monotherapy in the management of neuropathic pain in patients with peripheral neuropathy. 2108 11

Peripheral neuropathy (PN) is a common impairment which may impact upon quality of life (QoL). Neuropathic pain (NeP) occurs in up to 50% of patients with PN. We hypothesized that disability and impaired quality of life resulting from PN is primarily associated with presence of NeP. Our aim was to determine using prospectively identified PN patients presenting to a tertiary care neuromuscular clinic if presence of NeP (PN+NeP) had greater impact upon QoL than with absence of NeP (PN-NeP). A second aim was to identify if QoL varied based upon etiology of PN. We analyzed neuropathy severity (Toronto Clinical Neuropathy Score (TCSS)), pain quantity and quality (Visual Analogue Scale (VAS) pain score, Brief Pain Inventory (BPI)), QoL and health status measures (EuroQol Instrument 5 Domains (EQ-5D), Medical Outcomes Sleep Study Scale (MOSSS), Hospital Anxiety and Depression Scale (HADS), Short Form 36 Health Survey (SF-36)) and Health Assessment Questionnaire (HAQ) to determine impact of NeP. Although both cohorts were epidemiologically similar and had similar severity of PN, PN+NeP patients had considerably greater impairment for QoL, sleep efficacy, and features of anxiety and depression, leading to substantially greater health care resources utilization when compared to PN-NeP patients. The magnitude of NeP severity was the only explaining variable for increased impact upon QoL measures and diminishing overall wellbeing. Our results confirm that NeP is a primary indicator for worsening QoL and diminished overall wellbeing in PN patients. The etiology of PN did not influence levels of NeP-related compromise of QoL. Further studies are needed to determine optimal methods for management of PN+NeP patients subjected to a significant physiological, psychological and functional burden.
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PMID:The impact of pain in patients with polyneuropathy. 2253 45

Neuropathic pain is often accompanied by stress, anxiety and depression. Although there is evidence for involvement of corticotropin-releasing factor (CRF), the detailed neuronal basis of these pain-related mood alterations is unknown. This study shows that peripheral mononeuropathy was accompanied by changes in limbic forebrain CRF, but did not lead to changes in the functioning of the hypothalamo-pituitary-adrenal axis and the midbrain Edinger-Westphal centrally projecting (EWcp) neuron population, which play main roles in the organism's response to acute pain. Twenty-four days after chronic constriction injury (CCI) of the rat sciatic nerve, the oval bed nucleus of the stria terminalis (BSTov) contained substantially more Crf mRNA as did the central amygdala (CeA), which, in addition, possessed more CRF. In contrast, Crf mRNA and CRF contents of the hypothalamic paraventricular nucleus (PVN) were unaffected by CCI. Similarly, EWcp neurons, producing the CRF family member urocortin 1 (Ucn1) and constitutively activated by various stressors including acute pain, did not show an effect of CCI on Ucn1 mRNA or Ucn1. Also, the immediate early gene products cFos and deltaFosB in the EWcp were unaffected by CCI. These results indicate that neuropathic pain does not act via the HPA-axis or the EWcp, but includes a main role of Crf in the limbic system, which is in clear contrast to stressors like acute and chronic pain, which primarily act on the PVN and the EWcp.
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PMID:Experimental neuropathy increases limbic forebrain CRF. 2168 87

Neuropathic pain concurrent with mood disorder from peripheral nerve injury is a serious clinical problem that significantly affects quality of life. Recent studies have suggested that a lack of brain-derived neurotrophic factor (BDNF) in the limbic system may cause this pain-emotion. BDNF is induced in cultured neurons by 4-methylcatechol (4-MC), but the role of 4-MC-induced BDNF in pain-emotion is poorly understood. Thus, we assessed the possible involvement of BDNF in brain in depression-like behavior during chronic pain following peripheral nerve injury. In addition, we examined whether intracerebroventricular (i.c.v.) 4-MC prevents chronic pain in rats and produces an antidepressant effect. Sprague-Dawley rats implanted intracerebroventricularly with a PE-10 tube were subjected to chronic constriction injury (CCI). Pain was assessed by a reduction in paw withdrawal latency (PWL) to heat stimuli after CCI. We also used a forced swimming testing (FST; time of immobility, in seconds) from day 14 to day 21 after CCI. Modulation of pain and emotional behavior was performed by injection of PD0325901 (a MEK1/2 inhibitor). 4-MC (100 nM) was continuously administered i.c.v. for 3 days during the period from day 14 to day 21 after CCI. To block analgesic and antidepressant effects, anti-BDNF antibody or K252a (a TrkB receptor inhibitor) was injected in combination with 4-MC. Naloxone was also coadministered to confirm the analgesic effect of 4-MC. During the chronic stage after CCI, the rats showed a sustained decrease in PWL (thermal hyperalgesia) associated with extension of the time of immobility (depression-like behavior). PD0325901 significantly reduced the decrease in PWL and the increased time of immobility after CCI. The decreased PWL and increased time of immobility were also reduced by 4-MC and by treatment with an ERK1/2 inhibitor. These effects of 4-MC i.c.v. were reversed by anti-BDNF and K252a. The analgesic effect of 4-MC i.c.v. was also antagonized by naloxone. Based on these results, we suggest that a lack of BDNF and activation of ERK1/2 in the pain-emotion network in the CNS may be involved in depression-like behavior during chronic pain. 4-MC i.c.v. ameliorates chronic pain and depression-like behavior by producing of BDNF and normalization of ERK1/2 activation. Therefore, enhancement of BDNF may be a new treatment strategy for chronic pain associated with depression.
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PMID:Intracerebroventricular 4-methylcatechol (4-MC) ameliorates chronic pain associated with depression-like behavior via induction of brain-derived neurotrophic factor (BDNF). 2219 56

Neuropathic pain is strongly associated with mood disorders like anxiety and depression. Corticotropin-releasing factor (CRF) plays a prominent role in these disorders as it is up-regulated in limbic structures such as the amygdala, upon experimentally induced neuropathy. This review discusses recent literature on the role of CRF in pain processing and highlights the amygdala as a potential hot spot in supraspinal descending pain control. Many studies have demonstrated analgesic effects of CRF following local and systemic administration, but more recently also hyperalgesic effects were shown upon endogenous amygdalar CRF increase or by blocking the CRF type 1 receptor (CRFR1). On the basis of the reviewed literature, we postulate a central mechanism for pain control in which the amygdala plays a critical role by switching on and off chronic pain. In this mechanism, upon pain stimuli, CRFR1 in the amygdala is activated by CRF to induce hyperalgesia. When the activated CRFR1 is internalized (pain initiation), it triggers the translocation of the cytoplasmic CRF type 2 receptor (CRFR2) to the plasma membrane. Here, CRFR2 can be recruited by either high (pharmacological) concentrations of CRF or by endogenous CRFR2 ligands, the urocortins, leading to analgesia (pain termination). This on-off switching of pain is completed by redistribution of the CRF receptors to their initial activity state. We furthermore propose that in neuropathic pain, this mechanism is dysregulated and causes a state of permanent hyperalgesia, and present an integrative (patho)physiological model for the way disturbed CRF receptor signalling in the amygdala could initiate neuropathic pain.
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PMID:The amygdala, a relay station for switching on and off pain. 2233 28

Neuropathic pain and allodynia may arise from sensitization of central circuits. We report a mechanism of disinhibition-based central sensitization resulting from long-term depression (LTD) of GABAergic interneurons as a consequence of TRPV1 activation in the spinal cord. Intrathecal administration of TRPV1 agonists led to mechanical allodynia that was not dependent on peripheral TRPV1 neurons. TRPV1 was functionally expressed in GABAergic spinal interneurons and activation of spinal TRPV1 resulted in LTD of excitatory inputs and a reduction of inhibitory signaling to spinothalamic tract (STT) projection neurons. Mechanical hypersensitivity after peripheral nerve injury was attenuated in TRPV1(-/-) mice but not in mice lacking TRPV1-expressing peripheral neurons. Mechanical pain was reversed by a spinally applied TRPV1 antagonist while avoiding the hyperthermic side effect of systemic treatment. Our results demonstrate that spinal TRPV1 plays a critical role as a synaptic regulator and suggest the utility of central nervous system-specific TRPV1 antagonists for treating neuropathic pain.
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PMID:TRPV1 in GABAergic interneurons mediates neuropathic mechanical allodynia and disinhibition of the nociceptive circuitry in the spinal cord. 2263 22


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