"Together, these results suggest that α 2A -/α 2C -adrenoceptors and 5-HT 2 /5-HT 4 receptor-modulated mechanisms may be responsible for the antinociceptive effect of imipramine on visceral pain in rats. Despite the proven antinociceptive effects of antidepressants revealed by experimental studies in animals (Fishbain et al., 2000; Micó et al., 2006) and the clinical studies that recommend the use of antidepressants for the management of certain pain states (Onghena and Van Houdenhove, 1992; O'Malley et al., 2000; Saarto and Wiffen, 2010), the exact mechanism(s) of the analgesic actions of antidepressants remain unknown and require elucidation. The major mechanism of antidepressant-mediated antinociception has been suggested to be the blockade of the reuptake of monoamines via the inhibition of their specific transporters at the presynaptic membrane (Millan, 2002; Micó et al., 2006). "
[Show abstract][Hide abstract] ABSTRACT: It has been shown that imipramine, a tricyclic antidepressant (TCA), is a potent analgesic agent. However, the effect of imipramine on visceral pain has not been extensively investigated. In the current study, our aim was to characterize the putative analgesic effect of intravenous imipramine on visceral pain in rats. Our second aim was to assess the involvement of serotonergic (5-HT2, 3, 4) and noradrenergic (α2A, 2B, 2C) receptor subtypes in this putative antinociceptive effect of imipramine. Male Sprague Dawley rats (250-300 g) were implanted with venous catheters for drug administration and implanted with enamelled nichrome electrodes for electromyography of the external oblique muscles. Noxious visceral stimulation was applied via by colorectal distension (CRD). The visceromotor responses (VMRs) to CRD were quantified electromyographically before and after imipramine administration at 5, 15, 30, 60, 90 and 120 min. In the antagonist groups, the agents were administered 10 min before imipramine. The administration of imipramine (5-40 mg/kg) produced a dose-dependent reduction in VMR. The administration of yohimbine (a nonselective α2-adrenoceptor antagonist, 1 mg/kg), BRL-44408 (an α2A-adrenoceptor antagonist, 1 mg/kg) or MK-912 (an α2C-adrenoceptor antagonist, 300 μg/kg) but not imiloxan (an α2B-adrenoceptor antagonist, 1 mg/kg) inhibited the antinociceptive effect of imipramine (20 mg/kg). Additionally, ketanserin (a 5-HT2 receptor antagonist, 0.5, 1, and 2 mg/kg) and GR113808 (a 5-HT4 receptor antagonist, 1 mg/kg) enhanced and ondansetron (a 5-HT3 receptor antagonist, 0.5, 1, and 2 mg/kg) failed to alter the imipramine-induced antinociceptive effect. Our data demonstrated that, in the CDR-induced rat visceral pain model, intravenous imipramine appeared to have antinociceptive potential and that α2A-/α2C-adrenoceptors and 5-HT2/5-HT4 receptors may be responsible for the antinociceptive effect of imipramine on visceral pain in rats.
"TCAs are well-known drugs that inhibit norepinephrine and serotonin reuptake in the CNS, modulating sodium channels and augmenting dorsal root ganglion blockage by the inhibition of NMDA receptors.11,110 The efficacy of TCAs is established mainly in PHN.111,112 Antidepressive effects create a double hit to NP mechanism, since pain perception is highly increased with depression. TCAs are thought to have analgesic effects at dosages lower than required for depression. "
[Show abstract][Hide abstract] ABSTRACT: Cancer pain is a serious health problem, and imposes a great burden on the lives of patients and their families. Pain can be associated with delay in treatment, denial of treatment, or failure of treatment. If the pain is not treated properly it may impair the quality of life. Neuropathic cancer pain (NCP) is one of the most complex phenomena among cancer pain syndromes. NCP may result from direct damage to nerves due to acute diagnostic/therapeutic interventions. Chronic NCP is the result of treatment complications or malignancy itself. Although the reason for pain is different in NCP and noncancer neuropathic pain, the pathophysiologic mechanisms are similar. Data regarding neuropathic pain are primarily obtained from neuropathic pain studies. Evidence pertaining to NCP is limited. NCP due to chemotherapeutic toxicity is a major problem for physicians. In the past two decades, there have been efforts to standardize NCP treatment in order to provide better medical service. Opioids are the mainstay of cancer pain treatment; however, a new group of therapeutics called coanalgesic drugs has been introduced to pain treatment. These coanalgesics include gabapentinoids (gabapentin, pregabalin), antidepressants (tricyclic antidepressants, duloxetine, and venlafaxine), corticosteroids, bisphosphonates, N-methyl-D-aspartate antagonists, and cannabinoids. Pain can be encountered throughout every step of cancer treatment, and thus all practicing oncologists must be capable of assessing pain, know the possible underlying pathophysiology, and manage it appropriately. The purpose of this review is to discuss neuropathic pain and NCP in detail, the relevance of this topic, clinical features, possible pathology, and treatments of NCP.
OncoTargets and Therapy 04/2014; 7:599-618. DOI:10.2147/OTT.S60995 · 2.31 Impact Factor
"Amitriptyline, nortriptyline, and desipramine are antidepressants currently recommended as first-line therapies (Figure 2). Clinical experience indicates that TCAs can be efficacious in relieving neuropathic pain, although they display a relatively slow onset of action, and the medical literature shows that they do not work as well in patients with certain types of pain common in PHN (ie, burning pain or allodynia).18,62 TCAs are often poorly tolerated, and are associated with significant systemic adverse events and cardiac toxicity (Table 1), which require considerable caution when treating older patients, the population that is the most prevalent for developing PHN. "
[Show abstract][Hide abstract] ABSTRACT: An estimated one million individuals in the US are diagnosed with herpes zoster (HZ; shingles) each year. Approximately 20% of these patients will develop postherpetic neuralgia (PHN), a complex HZ complication characterized by neuropathic pain isolated to the dermatome that was affected by the HZ virus. PHN is debilitating, altering physical function and quality of life, and commonly affects vulnerable populations, including the elderly and the immunocompromised. Despite the availability of an immunization for HZ prevention and several approved HZ treatments, the incidence of PHN is increasing. Furthermore, management of the neuropathic pain associated with PHN is often suboptimal, and the use of available therapeutics may be complicated by adverse effects and complex, burdensome treatment regimens, as well as by patients' comorbidities and polypharmacy, which may lead to drug-drug interactions. Informed and comprehensive assessments of currently available pharmacological treatment options to achieve effective pain control in the primary care setting are needed. In this article, we discuss the situation in clinical practice, review currently recommended prevention and treatment options for PHN, and outline practical considerations for the management of this neuropathic pain syndrome, with a focus on optimal, individual-based treatment plans for use in the primary care setting.
Journal of Pain Research 03/2014; 7:125-132. DOI:10.2147/JPR.S57242
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