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Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system, which can severely impact patients' quality of life. The current-approved treatments for NP comprise of both centrally acting agents and topical drugs, including capsaicin 8% dermal patches, which is approved for the treatment of peripheral NP.
Learn More >Rheumatoid arthritis (RA) is often accompanied by joint pain and inflammation. Previous studies demonstrated that functional FcγRI was expressed in dorsal root ganglion neurons, and might contribute to pain in rodent models of antigen-induced arthritis (AIA). This study was performed to elucidate the roles of nociceptive neuronal FcγRI-coupled signaling in the development of joint pain in AIA.
Learn More >Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder that typically occurs in the limbs, usually the upper limb. CRPS usually develops from a peripheral event but its maintenance relies on changes within the central nervous system. While functional abnormalities in the thalamus and primary somatosensory cortex (S1) of the brain are some of the most consistently reported brain findings in CRPS, the mechanisms are yet to be explored in full, not least of all how these two regions interact and how they might relate to clinical deficits, such as the commonly reported poor tactile acuity in this condition. This study recruited 15 upper-limb CRPS subjects and 30 healthy controls and used functional magnetic resonance imaging (fMRI) to investigate infra-slow oscillations (ISOs) in critical pain regions of the brain in CRPS. As hypothesised, we found CRPS was associated with increases in resting signal intensity ISOs (0.03-0.06 Hz) in the thalamus contralateral to the painful limb in CRPS subjects. Interestingly, there was no such difference between groups in S1, however CRPS subjects displayed stronger thalamo-S1 functional connectivity than controls, and this was related to pain. As predicted, CRPS subjects displayed poor tactile acuity on the painful limb which, interestingly, was also related to thalamo-S1 functional connectivity strength. Our findings provide novel evidence of altered patterns of resting activity and connectivity in CRPS which may underlie altered thalamocortical loop dynamics and the constant perception of pain.
Learn More >The objective of this study was to examine if patients with migraine who responded sufficiently to acute treatment were significantly different from those who did not in terms of patient characteristics, treatment patterns, and patient level of impairment, and to identify characteristics associated with insufficient response.
Learn More >Clinical and experimental evidence supports the presence of several gender differences in the pain experience.
Learn More >Differences in pain processing, muscle structure and function have been reported in patients with low back pain (LBP) with different grades of pain chronicity.
Learn More >Interpreting randomized clinical trials (RCTs) is crucial to making decisions regarding the use of analgesic treatments in clinical practice. In this article, we report on an Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus meeting organized by the Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks (ACTTION), the purpose of which was to recommend approaches that facilitate interpretation of analgesic RCTs. We review issues to consider when drawing conclusions from RCTs, as well as common methods for reporting RCT results and the limitations of each method. These issues include the type of trial, study design, statistical analysis methods, magnitude of the estimated beneficial and harmful effects and associated precision, availability of alternative treatments and their benefit-risk profile, clinical importance of the change from baseline both within and between groups, presentation of the outcome data, and the limitations of the approaches used.
Learn More >Over the past number of years, N-methyl-D-aspartate (NMDA) inhibitory drugs, like ketamine, have been introduced as adjuvant treatments for postoperative acute pain, within a multimodal approach. A further extension of this strategy could be the use of opioids with NMDA receptor (NMDAr) antagonism activity for control of postoperative pain. Methadone has a unique pharmacodynamic profile: it is both a μ-agonist and an NMDAr-blocker.
Learn More >Synthetic opioids, including fentanyl and its analogues, have therapeutic efficacy in analgesia and anesthesia. However, their illicit use in the U.S. has increased, and contributed to the number one cause of death for adults 18-50 years old. Fentanyl and the heroin metabolite, morphine, induce respiratory depression that can be treated with the mu opioid receptor (MOR) antagonist, naloxone. With higher or more rapid dosing, fentanyl, more than morphine, causes chest wall rigidity, and can also induce rapid onset laryngospasm. Because non-MORs could mediate differing clinical manifestations, we examined the interactions of fentanyl and morphine at recombinant human neurotransmitter transporters, G protein-coupled receptors, and the NMDA glutamate receptor. Both drugs were agonists at MOR, kappa, and delta opioid receptors. Morphine had little or no affinity at other human receptors and transporters (Ki or IC value >100μM). However, fentanyl had Ki values of 1,407nM and 1,100nM at α1A and α1B adrenoceptor subtypes, respectively, Ki values of 1,049nM and 1,670nM at dopamine D4.4 and D1 receptor subtypes, respectively, and also blocked [H]neurotransmitter uptake by the vesicular monoamine transporter 2 (VMAT2) (IC = 911nM). Pharmacokinetic models indicate that these Ki and IC values are pharmacologically relevant. Fentanyl had little affinity for other receptors or transporters. Thus, noradrenergic disposition at specific receptor subtypes in relevant organs may play a role in respiratory and cardiothoracic effects of fentanyl. Data suggest that less selective fentanyl receptor pharmacology could play a role in the different clinical effects of morphine compared to fentanyl, including fentanyl-induced deaths following illicit use. SIGNIFICANCE STATEMENT: The synthetic opioid, fentanyl, induces different clinical effects including rapid onset muscular rigidity, vocal cord closure and rapid death, than the heroin metabolite, morphine. Our data indicate for the first time that the two drugs have very different effects at recombinant human neurotransmitter receptors and transporters that might explain those clinical differences.
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