Articles: hyperalgesia.
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Randomized Controlled Trial
Study protocol for a randomised, double-blinded, placebo-controlled, clinical trial of S-ketamine for pain treatment in patients with chronic pancreatitis (RESET trial).
Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids. However, opioids often have limited efficacy. Moreover, side effects are common and bothersome. Hence, novel approaches to control pain associated with CP are highly desirable. Sensitisation of the central nervous system is reported to play a key role in pain generation and chronification. Fundamental to the process of central sensitisation is abnormal activation of the N-methyl-D-aspartate receptor, which can be antagonised by S-ketamine. The RESET trial is investigating the analgaesic and antihyperalgesic effect of S-ketamine in patients with CP. ⋯ The protocol is approved by the North Denmark Region Committee on Health Research Ethics (N-20130040) and the Danish Health and Medicines Authorities (EudraCT number: 2013-003357-17). The results will be disseminated in peer-reviewed journals and at scientific conferences.
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Journal of pain research · Jan 2015
ReviewBuprenorphine - an attractive opioid with underutilized potential in treatment of chronic pain.
Despite proven clinical utility, buprenorphine has not been used widely for the treatment of chronic pain. Questions about "ceiling effect" or bell-shaped curve observed for analgesia in preclinical studies and potential withdrawal issues on combining with marketed μ-agonists continue to hinder progress in expanding full potential of buprenorphine in the treatment of cancer and noncancer pain. Mounting evidence from clinical studies and conclusions drawn by a panel of experts strongly support superior safety and efficacy profile of buprenorphine vs marketed opioids. ⋯ The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. The buprenorphine pharmacology also allows it to be combined with other μ-receptor opioids for additivity in efficacy. Transdermal delivery products of buprenorphine have been preferred choices for the management of pain but new delivery options are under investigation for the treatment of both opioid dependence and chronic pain.
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Bradykinin is a neuropeptide released after tissue damage which plays an important role in inflammatory pain. The up-regulation of the bradykinin B1 receptor in response to inflammation makes it an attractive target for drug development. Aim was to investigate if the selective B1 receptor antagonist BI113823 reduces inflammation-induced mechanical hyperalgesia and if the effect is mediated via peripheral and/or spinal B1 receptor antagonism. ⋯ The selective bradykinin B1 receptor antagonist BI113823 reduces CFA-induced mechanical hyperalgesia which is mediated via antagonism of peripheral as well as spinal bradykinin B1 receptors. The selective modulation of CFA-sensitized spinal NS neurons by BI113823 could be a promising property for the treatment of inflammatory pain.
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Nummular headache (NH) is most commonly a localized unifocal headache; however, some patients infrequently exhibit multifocal symptomatic painful head areas retaining all features of NH. We present the pressure pain sensitivity map of an adolescent with multifocal NH. ⋯ This is the first pain sensitivity map of a patient with multifocal NH. Our results support peripheral mechanisms are maintained in multifocal NH.
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The activation of alpha-7 nicotinic acetylcholine receptors (α7-nAchRs) are currently being considered as novel therapeutic approaches for managing hyperalgesia in inflammation and chronic neuropathic pain, but the role of a7-nAChRs on opioids induced hyperalgesia remain unknown. The present study investigated the effects of α7-nAChRs selective agonists PHA-543613 and type II positive allosteric modulators (PAMs) PNU-120596 in remifentanil induced postoperative hyperalgesia. As the results shown, intrathecal treatment with both α7-nAChRs agonists and type II PAMs could attenuate remifentanil induced hyperalgesia by increasing paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). ⋯ Our data indicated that activation of α7-nAchRs decreased the proinflammatory cytokines (TNF-α, IL-6) and p-NR2B protein level in the spinal cord. The depression of the increased levels of proinflammatory cytokines and p-NR2B after remifentanil treatment may contribute to the anti-hyperalgesia effects of PHA-543613and PNU-120596 via α7-nAChRs. Therefore, our findings demonstrated that α7-nAChRs may be potential candidates for treating opioids induced hyperalgesia.