Articles: neuralgia.
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Randomized Controlled Trial
NRD.E1, an innovative non-opioid therapy for painful diabetic peripheral neuropathy - a randomised proof of concept study.
Painful diabetic peripheral neuropathy (PDPN) affects up to 26% of patients with diabetes mellitus, with major impacts on their general health and well-being. Most available drugs fail to deliver acceptable pain reduction in the majority of patients and are often poorly tolerated. NRD.E1 is a novel product that has shown anti-nociceptive preclinical effects and good tolerability in healthy volunteer studies. ⋯ NRD.E1 is a novel non-opioid therapeutic which is being developed for the treatment of PDPN. In this randomized, controlled, dose-finding, Proof of Concept study, NRD.E1 induced a clinically relevant pain reduction and it was well tolerated. Available data suggest that NRD.E1 has at least similar efficacy and better tolerability than the currently available therapies, potentially offering a promising new therapeutic option to patients with PDPN and possibly other neuropathic pain indications.
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Intrathecal application of contulakin-G (CGX), a conotoxin peptide and a neurotensin analogue, has been demonstrated to be safe and potentially analgesic in humans. However, the mechanism of action for CGX analgesia is unknown. We hypothesized that spinal application of CGX produces antinociception through activation of the presynaptic neurotensin receptor (NTSR)2. ⋯ Anatomical studies demonstrated coexpression of NTSR2 and Cav2.3 in dorsal root ganglion neurons. Finally, synaptic fractionation and slice electrophysiology recordings confirmed a predominantly presynaptic effect. Together, these data reveal a nonopioid pathway engaged by a human-tested drug to produce antinociception.
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We previously established a macaque model of central post-stroke pain (CPSP) and confirmed the involvement of increased activity of the posterior insular cortex (PIC) and secondary somatosensory cortex (SII) to somatosensory stimuli in mechanical allodynia by a combination of imaging techniques with local pharmacological inactivation. However, it is unclear whether the same intervention would be effective for thermal hyperalgesia. Therefore, using the macaque model, we examined behavioural responses to thermal stimuli following pharmacological inactivation of the PIC/SII. ⋯ CPSP is caused by stroke lesions in the sensory system and characterized by mechanical allodynia or thermal hyperalgesia. Inactivation of the PIC/SII has an analgesic effect on mechanical allodynia; however, it is not clear whether the same intervention could reduce thermal hyperalgesia. Here, using the macaque model, we demonstrated that inactivation of these cortices reduces hypersensitivity to thermal stimuli. This result emphasizes that increased PIC/SII activity can contribute to abnormal pain of multiple modalities.
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Experimental studies have suggested that nitrous oxide-induced analgesia depends on interactions with opioids. On the basis of these results, we hypothesized that the effects of inhaled nitrous oxide/oxygen (N 2 O/O 2 ) 50%-50% equimolar mixture (EMONO) on patients with neuropathic pain would be higher in those receiving concomitant opioids. To test this hypothesis, we did exploratory post hoc analyses of our recently published ProtoTOP study to compare the effects of EMONO and placebo in patients with or without concomitant opioid treatment. ⋯ The proportion of patients with at least 30% pain reduction and of those reporting an overall improvement with the Patient Global Impression of Change were significantly higher only in this population of patients. In conclusion, these results complement our previous analyses with the identification of a specific population of responders to EMONO inhalation in patients with neuropathic pain. As suggested by experimental studies, we hypothesized that these long-lasting analgesic effects could depend on the anti-N-methyl-D-aspartate properties of N 2 O.
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Neuropathic pain is a prevalent and burdensome condition. While oral medical therapies are the first-line treatment for refractory neuropathic pain, in some cases, infusion therapy may be employed. This article is a systematic review of recent publications regarding epidemiologic, pathophysiologic, diagnostic, and therapeutic advancements in the treatment of neuropathic pain using intravenous infusion therapy. Special consideration will be given to relevant and practically used agents and available information on outcomes. ⋯ Individuals with neuropathic pain from various etiologies (e.g. trigeminal neuralgia, post-herpetic neuralgia, diabetic neuropathy) often find short-term relief from infusion therapies. However, it is difficult to generalize the findings of these studies to form a standard treatment regimen. The purpose of this paper is to provide clinicians an up-to-date summary of recent literature regarding several infusion therapies in treating neuropathic pain.