Accepted

Skin pain resulting from mechanical compression is one of the most common pains in daily life and the indispensable information for electronic skin to perceive external signals. The external mechanical stimuli are transduced into impulses and transmitted via nerve fiber, and finally, the sensation is perceived via the procession of the nerve system. However, the mathematical mechanism for pain sensation due to mechanical stimuli remains unclear. In this paper, a mathematical model for skin pain sensation under compression is established, in which the Flament solution, the revised Hodgkin-Huxley model, and the mathematical model gate control theory are considered simultaneously. The proposed model includes three parts: a mechanical model of skin compression, a model of transduction, and a model of modulation and perception. It is demonstrated that the pain sensation degree increases with the compression amplitude and decreases with deeper nociceptor location in the skin. With the help of the proposed model, the quantitative relationship between compression pain sensation and external mechanical stimuli is revealed, which has a significant benefit in promoting the design and mechanism research of electronic skin with pain perception function.

In complex diseases, the phenotypic variability can be explained by genetic variation (G), environmental stimuli (E), and interaction of genetic and environmental factors (G-by-E effects), among which the contribution G-by-E remains largely unknown. In this study, we focus on ten major neuropsychiatric disorders using data for 138,383 United States families with 404,475 unique individuals. We show that, while gene-environment interactions account for only a small portion of the total phenotypic variance for a subset of disorders (depression, adjustment disorder, substance abuse), they explain a rather large portion of the phenotypic variation of the remaining disorders: over 20% for migraine and close to or over 30% for anxiety/phobic disorder, attention-deficit/hyperactivity disorder, recurrent headaches, sleep disorders, and post-traumatic stress disorder. In this study, we have incorporated-in the same analysis-clinical data, family pedigrees, the spatial distribution of individuals, their socioeconomic and demographic confounders, and a collection of environmental measurements.

Buprenorphine, a novel opioid with complex pharmacology, is effective for treating pain and is qualitatively safer than high dose full agonist opioid therapy; but transitioning to buprenorphine can be technically complex and carries some risk of precipitated withdrawal. We report our clinic's experience converting 36 patients with sickle cell disease from full agonist opioids to buprenorphine using a method developed in the past ten years. Thirty of these patients were induced using a standard outpatient protocol and six were induced during medical admissions. Typically, patients were on high-dose chronic opioid therapy with inadequate response; often with very high acute care utilization. Unlike prior case series, the method of induction, dosing, and management of withdrawal are detailed, as are post-induction adverse events. There were seven adverse events in the first three days following standard induction, two of which were judged to be definitely related to the induction but none with any lasting sequelae. At six months follow-up, five participants had discontinued buprenorphine (16.67%), and overall acute care visits dropped from a mean of 10.50 (SD 11.35) in the six months pre-induction to 2.89 (SD 3.40) in the six months post induction. In an appropriately interdisciplinary care setting, buprenorphine shows promise as a safe alternative to chronic opioid therapy with early evidence of benefit for high utilizing patients with SCD. This article is protected by copyright. All rights reserved.

Spinal analgesia is recommended for intractable cancer pain. Morphine-clonidine and sufentanil-clonidine are often used in association in intrathecal drug delivery systems, injected by intraabdominal pumps. To refill these pumps and to limit patient transport, it may be necessary to ship the mixtures in polypropylene syringes to peripheral establishments located near patient homes. The purpose of this study is to determine the stability of morphine-clonidine and sufentanil-clonidine mixtures in polypropylene syringes to ensure the best and safest transport conditions and in implantable pumps for intrathecal use.

The spinal N-methyl-D-aspartate receptor (NMDAR), particularly their subtypes NR2A and NR2B, plays pivotal roles in neuropathic and inflammatory pain. However, the roles of NR2A and NR2B in orofacial pain and the exact molecular and cellular mechanisms mediating nervous system sensitization are still poorly understood. Here, we exhaustively assessed the regulatory effect of NMDAR in mediating peripheral and central sensitization in orofacial neuropathic pain. Von-Frey filament tests showed that the inferior alveolar nerve (IANX) induced ectopic allodynia behavior in the whisker pad of mice. Interestingly, mechanical allodynia was reversed in mice lacking NR2A and NR2B. IANX also promoted the production of peripheral sensitization-related molecules, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, brain-derived neurotrophic factor (BDNF), and chemokine upregulation (C-C motif) ligand 2 (CCL2), and decreased the inward potassium channel (Kir) 4.1 on glial cells in the trigeminal ganglion, but NR2A conditional knockout (CKO) mice prevented these alterations. In contrast, NR2B CKO only blocked the changes in Kir4.1, IL-1β, and TNF-α and further promoted the production of CCL2. Central sensitization-related c-fos, glial fibrillary acidic protein (GFAP), and ionized calcium-binding adaptor molecule 1 (Iba-1) were promoted and Kir4.1 was reduced in the spinal trigeminal caudate nucleus by IANX. Differential actions of NR2A and NR2B in mediating central sensitization were also observed. Silencing of NR2B was effective in reducing c-fos, GFAP, and Iba-1 but did not affect Kir4.1. In contrast, NR2A CKO only altered Iba-1 and Kir4.1 and further increased c-fos and GFAP. Gain-of-function and loss-of-function approaches provided insight into the differential roles of NR2A and NR2B in mediating peripheral and central nociceptive sensitization induced by IANX, which may be a fundamental basis for advancing knowledge of the neural mechanisms' reaction to nerve injury.