BackgroundDorsal root ganglion neuron-derived immortal cell lines including ND7/23 and F-11 cells have been used extensively as in vitro model systems of native peripheral sensory neurons. However, while it is clear that some sensory neuron-specific receptors and ion channels are present in these cell lines, a systematic comparison of the molecular targets expressed by these cell lines with those expressed in intact peripheral neurons is lacking.ResultsIn this study, we examined the expression of RNA transcripts in the human neuroblastoma-derived cell line, SH-SY5Y, and two dorsal root ganglion hybridoma cell lines, F-11 and ND7/23, using Illumina next-generation sequencing, and compared the results with native whole murine dorsal root ganglions. The gene expression profiles of these three cell lines did not resemble any specific defined dorsal root ganglion subclass. The cell lines lacked many markers for nociceptive sensory neurons, such as the Transient receptor potential V1 gene, but expressed markers for both myelinated and unmyelinated neurons. Global gene ontology analysis on whole dorsal root ganglions and cell lines showed similar enrichment of biological process terms across all samples.ConclusionsThis paper provides insights into the receptor repertoire expressed in common dorsal root ganglion neuron-derived cell lines compared with whole murine dorsal root ganglions, and illustrates the limits and potentials of these cell lines as tools for neuropharmacological exploration.

Background Location-based augmented reality (AR) games, such as Pokémon GO and Harry Potter: Wizards Unite, have been shown to have a beneficial impact on the physical activity, social connectedness, and mental health of their players. In March 2020, global social distancing measures related to the COVID-19 pandemic prompted the AR games developer Niantic Inc to implement several changes to ensure continued player engagement with Pokémon GO and Harry Potter: Wizards Unite. We sought to examine how the physical and mental well-being of players of these games were affected during the unprecedented COVID-19 restriction period as well as how their video game engagement was affected. Objective The aims of this study were to examine the impact of COVID-19–related social restrictions on the physical and mental well-being of AR game players; to examine the impact of COVID-19–related social restrictions on the use of video games and motivations for their use; and to explore the potential role of AR games (and video games in general) in supporting well-being during COVID-19–related social restrictions. Methods A mixed methods web-based self-reported survey was conducted in May 2020, during which COVID-19–related social restrictions were enforced in many countries. Participants were recruited on the web via four subreddits dedicated to Pokémon GO or Harry Potter: Wizards Unite. Data collected included quantitative data on demographics, time spent playing video games, physical activity, and mental health; qualitative data included motivations to play and the impact of video games on mental health during COVID-19 lockdown. Results We report results for 2004 participants (1153/1960 male, 58.8%, average age 30.5 years). Self-reported physical activity during COVID-19–related social restrictions significantly decreased from 7.50 hours per week on average (SD 11.12) to 6.50 hours (SD 7.81) (P<.001). More than half of the participants reported poor mental health (925/1766, 52.4%; raw World Health Organization–5 Well-Being Index score <13). Female gender, younger age, and reduced exercise were significant predictors of poor mental health. Participants reported a significant increase in video game play time from 16.38 hours per week on average (SD 19.12) to 20.82 hours (SD 17.49) (P<.001). Approximately three quarters of the participants (n=1102/1427, 77.2%) reported that playing video games had been beneficial to their mental health. The changes made to Pokémon GO and Harry Potter: Wizards Unite were very well received by players, and the players continued to use these games while exercising and to maintain social connection. In addition to seeking an escape during the pandemic and as a form of entertainment, participants reported that they used video games for emotional coping and to lower stress, relax, and alleviate mental health conditions. Conclusions AR games have the potential to promote physical and mental health during the COVID-19 pandemic. Used by populations under isolation and distress, these games can improve physical and mental health by providing virtual socialization, sustained exercise, temporal routine, and mental structure. Further research is needed to explore the potential of AR games as digital behavioral interventions to maintain human well-being in the wider population.

Burn injury is a cause of significant mortality and morbidity worldwide and is frequently associated with severe and long-lasting pain that remains difficult to manage throughout recovery. We characterised a mouse model of burn-induced pain using pharmacological and transcriptomic approaches. Mechanical allodynia elicited by burn injury was partially reversed by meloxicam (5 mg/kg), gabapentin (100 mg/kg) and oxycodone (3 and 10 mg/kg), while thermal allodynia and gait abnormalities were only significantly improved by amitriptyline (3 mg/kg) and oxycodone (10 mg/kg). The need for relatively high opioid doses to elicit analgesia suggested a degree of opioid resistance, similar to that shown clinically in burn patients. We thus assessed the gene expression changes in dorsal root ganglion neurons and pathophysiological mechanisms underpinning burn injury-induced pain using a transcriptomic approach. Burn injury was associated with significantly increased expression of genes associated with axon guidance, neuropeptide signalling, behavioural defence response and extracellular signalling, confirming a mixed neuropathic and inflammatory aetiology. Notably, among the pain-related genes that were upregulated post-injury was the cholecystokinin 2 receptor (Cckbr), a G protein-coupled receptor known as a pain target involved in reducing opioid effectiveness. Indeed, the clinically used cholecystokinin receptor antagonist proglumide (30 mg/kg) was effective at reversing mechanical allodynia, with additional analgesia evident in combination with low-dose oxycodone (1 mg/kg), including significant reversal of thermal allodynia. These findings highlight the complex pathophysiological mechanisms underpinning burn injury-induced pain and suggest that cholecystokinin-2 receptor antagonists may be useful clinically as adjuvants to decrease opioid requirements and improve analgesic management.

Please cite this article as: Yin K, Zimmermann K, Vetter I, Lewis RJ, Therapeutic opportunities for targeting cold pain pathways, Biochemical Pharmacology (2014), http://dx.doi. org/10.1016/j.bcp.2014.09.024 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Background Having patients self-manage their health conditions is a widely promoted concept, but many patients struggle to practice it effectively. Moreover, few studies have analyzed the nature of work required from patients and how such work fits into the context of their daily life. Objective This study aimed to review the characteristics of patient work in adult patients. Patient work refers to tasks that health conditions impose on patients (eg, taking medications) within a system of contextual factors. Methods A systematic scoping review was conducted using narrative synthesis. Data were extracted from PubMed, Excerpta Medica database (EMBASE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), and PsycINFO, including studies from August 2013 to August 2018. The included studies focused on adult patients and assessed one or more of the following: (1) physical health–related tasks, (2) cognitive health–related tasks, or (3) contextual factors affecting these tasks. Tasks were categorized according to the themes that emerged: (1) if the task is always visible to others or can be cognitive, (2) if the task must be conducted collaboratively or can be conducted alone, and (3) if the task was done with the purpose of creating resources. Contextual factors were grouped according to the level at which they exert influence (micro, meso, or macro) and where they fit in the patient work system (the macroergonomic layer of physical, social, and organizational factors; the mesoergonomic layer of household and community; and the microergonomic triad of person-task-tools). Results In total, 67 publications were included, with 58 original research articles and 9 review articles. A variety of patient work tasks were observed, ranging from physical and tangible tasks (such as taking medications and visiting health care professionals) to psychological and social tasks (such as creating coping strategies). Patient work was affected by a range of contextual factors on the micro, meso, or macro levels. Our results indicate that most patient work was done alone, in private, and often imposing cognitive burden with low amounts of support. Conclusions This review sought to provide insight into the work burden of health management from a patient perspective and how patient context influences such work. For many patients, health-related work is ever present, invisible, and overwhelming. When researchers and clinicians design and implement patient-facing interventions, it is important to understand how the extra work impacts one’s internal state and coping strategy, how such work fits into daily routines, and if these changes could be maintained in the long term.

1The NLRP3 inflammasome is a multi-protein complex that assembles in response to 2 tissue damage or infection, triggering activation of caspase-1, an enzyme that converts 3 interleukin (IL)-1β into its active form. A role for the NLRP3 inflammasome is 4 emerging in inflammatory pain, but its influence in other pain types is largely 5 unexamined. Therefore the aim of this study was to assess the role of the NLRP3 6 inflammasome and its downstream product caspase-1 in a mouse model of burn-7 induced pain. A superficial burn was induced on the plantar surface of the left hind 8 paw using a hot plate set at 52.5 °C for 25 seconds. Development of acute burn-9 induced mechanical allodynia, thermal allodynia, edema and weight bearing changes 10 was assessed in Nlrp3 -/-and caspase-1-deficient (Ice -/-

Spider venom is a novel source of disulfide-rich peptides with potent and selective activity at voltage-gated sodium channels (NaV). Here, we describe the discovery of μ-theraphotoxin-Pme1a and μ/δ-theraphotoxin-Pme2a, two novel peptides from the venom of the Gooty Ornamental tarantula Poecilotheria metallica that modulate NaV channels. Pme1a is a 35 residue peptide that inhibits NaV1.7 peak current (IC50 334 ± 114 nM) and shifts the voltage dependence of activation to more depolarised membrane potentials (V1/2 activation: Δ = +11.6 mV). Pme2a is a 33 residue peptide that delays fast inactivation and inhibits NaV1.7 peak current (EC50 > 10 μM). Synthesis of a [+22K]Pme2a analogue increased potency at NaV1.7 (IC50 5.6 ± 1.1 μM) and removed the effect of the native peptide on fast inactivation, indicating that a lysine at position 22 (Pme2a numbering) is important for inhibitory activity. Results from this study may be used to guide the rational design of spider venom-derived peptides with improved potency and selectivity at NaV channels in the future.

Location-based augmented reality games, used in several smartphone devices, have the potential to improve health outcomes by transforming gaming from a sedentary leisure pursuit to an active leisure pursuit thus having positive physical, psychological and social implications. We consider two games, Harry Potter: Wizards Unite and Pokémon GO, by qualitatively mapping both psychographic and behavioral data to profile groups of players to fully understand how we can better design location-based augmented reality exergames to improve exercise and health. Data was collected through an online open-ended, text-box survey (proforma) hosted on Qualtrics, with participants reached via virtual snowballing. The proforma was posted on four subreddit forums dedicated to Harry Potter: Wizards Unite and Pokémon GO for two weeks, and 1052 participants responded. Our study aligns with a deductive category application, with all highlighted excerpts coded using a predetermined coding scheme. Overall, three themes were identified: 1) Player Loyalty, 2) Player Involvement and 3) Player Constraints. We conclude that psychographic constraints experienced can negatively influence player preference and behavior. However, psychographic enablers such as player involvement with the franchise and player loyalty toward the brand can act to sustain continued gameplay across different player types and should not be underestimated as a powerful influence in decision-making, choice behavior, and behavior change (to improve exercise and health).