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Although the great majority of patients who take opioids for chronic pain use them appropriately and to good effect, a certain minority will develop the problematic outcome of opioid use disorder (OUD). Patient characteristics associated with the development of OUD in patients with chronic pain have been described, however relatively unexplored is how sensitivity to pain is associated with OUD outcomes.
Learn More >Migraine with aura is known to increase the risk of cardiovascular disease (CVD). The absolute contribution of migraine with aura to CVD incidence in relation to other CVD risk factors remains unclear.
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.
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 >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 >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 >To examine whether sleep disturbance modifies the association between physical activity and incident pain.
Learn More >The aetiology of painful diabetic neuropathy is unclear. We have evaluated vitamin D levels in diabetic patients with and without painful neuropathy. Forty-three patients with type 1 diabetes and painless (DPN) (n = 20) or painful (PDN) (n = 23) neuropathy and 14 non-diabetic healthy control subjects (C) underwent assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal confocal microscopy (CCM) and measurement of serum 25(OH)D. There were no significant differences for age, BMI, HbA1c, lipids, neurological deficits, QST, electrophysiology, intra-epidermal nerve fibre density (IENFD) and corneal nerve morphology between patients with DPN and PDN. Both positive (hyperalgesia and allodynia) and negative symptoms (paraesthesia and numbness) of diabetic neuropathy were greater in PDN compared to DPN (P = 0.009 and P = 0.02 respectively). Serum 25(OH)D level were significantly lower in PDN (24.0 ± 14.1 ng/mL) compared to DPN (34.6 ± 15.0 ng/mL, P = 0.01) and controls (34.1 ± 8.6 ng/mL, P = 0.03). The odds ratio in favour of painful diabetic neuropathy was 9.8 (P = 0.003 (95% CI 2.2-76.4) for vitamin D deficiency (<20 ng/mL) and 4.4 (P = 0.03 [95% CI 1.1-19.8]) for vitamin D insufficiency (<30 ng/mL). This study suggests that vitamin D deficiency and insufficiency are associated with painful diabetic neuropathy. This article is protected by copyright. All rights reserved.
Learn More >Opioid use has increased to epidemic levels over the past decade within the United States, particularly among vulnerable populations. This retrospective study aimed to evaluate rates of prolonged opioid use in the Veteran population after thoracic surgery and identify specific risk clusters.
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