<b><i>Introduction:</i></b> We investigated the possibilities and opportunities for using wearable devices that measure physical activity and physiometric signals in conjunction with ecological momentary assessment (EMA) data to improve the assessment and treatment of pain. <b><i>Methods:</i></b> We considered studies with cross-sectional and longitudinal designs as well as interventional or observational studies correlating pain scores with measures derived from wearable devices. A search was also performed on studies that investigated physical activity and physiometric signals among patients with pain. <b><i>Results:</i></b> Few studies have assessed the possibility of incorporating wearable devices as objective tools for contextualizing pain and physical function in free-living environments. Of the studies that have been conducted, most focus solely on physical activity and functional outcomes as measured by a wearable accelerometer. Several studies report promising correlations between pain scores and signals derived from wearable devices, objectively measured physical activity, and physical function. In addition, there is a known association between physiologic signals that can be measured by wearable devices and pain, though studies using wearable devices to measure these signals and associate them with pain in free-living environments are limited. <b><i>Conclusion:</i></b> There exists a great opportunity to study the complex interplay between physiometric signals, physical function, and pain in a real-time fashion in free-living environments. The literature supports the hypothesis that wearable devices can be used to develop reproducible biosignals that correlate with pain. The combination of wearable devices and EMA will likely lead to the development of clinically meaningful endpoints that will transform how we understand and treat pain patients.

A single intrathecal dose of adenosine 2A receptor (A2AR) agonist was previously reported to produce a multi-week reversal of allodynia in a chronic constriction injury (CCI) model of neuropathic pain. We aimed to determine if this long-term reversal was induced by A2AR agonism versus more generalized across adenosine receptor subtypes, and begin to explore the intracellular signaling cascades involved. In addition, we sought to identify whether the enduring effect could be extended to other models of neuropathic pain. We tested an A1R and A2BR agonist in CCI and found the same long duration effect with A2BR but not A1R agonism. An A2AR agonist (ATL313) produced a significant long-duration reversal of mechanical allodynia induced by long established CCI (administered 6 wk after surgery), spinal nerve ligation and sciatic inflammatory neuropathy. To determine if ATL313 had a direct effect on glia, ATL313 was coadministered with lipopolysaccharide to neonatal microglia and astrocytes in vitro. ATL313 significantly attenuated TNFα production in both microglia and astrocytes but had no effect on LPS induced IL-10. Protein kinase C significantly reversed the ATL313 effects on TNF in vitro in microglia and astrocytes, while a protein kinase A inhibitor only effected microglia. Both intrathecal PKA and PKC inhibitors significantly reversed the effect of the A2AR agonist on neuropathic allodynia. Therefore, A2AR agonists administered IT remain an exciting novel target for the treatment of neuropathic pain.

No abstract

Introduction: Methadone, a synthetic narcotic, is widely used both in adults and children for pain control and as a replacement drug in opioid use disorder to prevent craving and withdrawal. To support clinical pharmacokinetic trials in neonates, infants, and children, the authors developed and validated a novel, automated, highly sensitive liquid chromatography–electrospray–tandem mass spectrometry ionization (LC-ESI-MS/MS) method for the quantification of methadone and its metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenylpyraline (EMDP), in samples collected as dried blood spots. Methods: Blood was spiked with different concentrations of methadone, EDDP, and EMDP, and blood drops were applied to filter paper cards. Punches of 6.4 mm were removed from the cards, and 600 µL of protein precipitation solution (methanol/0.2M ZnSO4, 7:3, vol/vol) containing the internal standards (methadone-d9 and EDDP-d5) at a concentration of 1 mcg/L was added. The extracts were analyzed using LC-ESI-MS/MS in combination with online extraction. The mass spectrometer was run in the positive multiple reaction monitoring mode, and the total run time was 3.2 minutes. Results: For the dried blood spots, the assay has a lower limit of quantification of 0.1 mcg/L for methadone, EDDP, and EMDP. The range of reliable response for methadone for the ion transition m/z = 310.2→265.1 was 0.1–100 mcg/L and for the ion transition m/z = 310.2→223.1 5–1000 mcg/L. For EDDP, on the range of reliable response for the ion transition, m/z = 278.2→234.3 was 0.1–100 mcg/L and for the ion transition m/z = 278.2→186.1 5–1000 mcg/L. The calibration range for EMDP was 0.1–100 mcg/L. Accuracy (85%–115%) and imprecision (<15%) met predefined acceptance criteria. Discussion: This assay allows for the measurement of small volume blood samples without the need for an intravenous blood draw, and thus, it is suitable for pharmacokinetics studies and therapeutic drug monitoring in pediatric patients.