Effects of (2<i>R</i>,6<i>R</i>)-hydroxynorketamine in assays of acute pain-stimulated and pain-depressed behaviors in mice

by Todd M. Hillhouse, Kaitlyn J. Partridge, Patrick I. Garrett, Sarah C. Honeycutt, Joseph H. Porter

Ketamine has been shown to produce analgesia in various acute and chronic pain states; however, abuse liability concerns have limited its utility. The ketamine metabolite (2R,6R)-hydroxynorketamine (HNK) has been shown to produce antidepressant-like effects similar to ketamine without abuse liability concerns. (2R,6R)-HNK produces sustained analgesia in models of chronic pain, but has yet to be evaluated in models of acute pain. The present study evaluated the efficacy of acute (2R,6R)-HNK administration (one injection) in assays of pain-stimulated (52- and 56-degree hot plate test and acetic acid writhing) and pain-depressed behavior (locomotor activity and rearing) in male and female C57BL/6 mice. In assays of pain-stimulated behaviors, (2R,6R)-HNK (1–32 mg/kg) failed to produce antinociception in the 52- and 56-degree hot plate and acetic acid writhing assays. In assays of pain-depressed behaviors, 0.56% acetic acid produced a robust depression of locomotor activity and rearing that was not blocked by pretreatment of (2R,6R)-HNK (3.2–32 mg/kg). The positive controls morphine (hot plate test) and ketoprofen (acetic acid writhing, locomotor activity, and rearing) blocked pain-stimulated and pain-depressed behaviors. Finally, the effects of intermittent (2R,6R)-HNK administration were evaluated in 52-degree hot plate and pain-depressed locomotor activity and rearing. Intermittent administration of (2R,6R)-HNK also did not produce antinociceptive effects in the hot plate or pain-depressed locomotor activity assays. These results suggest that (2R,6R)-HNK is unlikely to have efficacy in treating acute pain; however, the efficacy of (2R,6R)-HNK in chronic pain states should continue to be evaluated.

The impact of the newly developed school-based ‘Digital Health Contact’—Evaluating a health and wellbeing screening tool for adolescents in England

by Alice Porter, Katrina d’Apice, Patricia Albers, Nicholas Woodrow, Hannah Fairbrother, Katie Breheny, Clare Mills, Sarah Tebbett, Frank De Vocht

Introduction

Supporting adolescents with their health and wellbeing is an international public health priority. Schools are well placed to universally detect unmet health needs and support pupils. This study aimed to evaluate the effectiveness of a digital health and wellbeing screening tool, called the ‘Digital Health Contact’ (DHC) implemented in schools in the East Midlands of England. The DHC, delivered by Public Health Nurses (School Nurses) (PHN(SN)), aims to identify pupils with unmet health needs (via a ‘red flag’ system) and provide appropriate support.

Materials and methods

Using data from 22 schools which took part in the DHC and 14 schools which did not take part, across three academic years (2018–2020), we conducted a controlled interrupted timeseries analysis with negative binomial regression to explore the effect of the DHC on the number of annual referrals to PHN(SN). Using DHC data from 164 pupils, we further conducted a Difference-in-Difference analysis to explore the impact of ‘red flag’ and referral via the DHC in Year 9 (age 13–14) on the number of red flags in Year 11 (age 15–16).

Results

Across all schools, the mean annual number of referrals increased over the three year follow-up period. In the adjusted model, the number of referrals was comparable between schools taking part in the DHC and non-participating schools (0.15 referrals [95% CI -0.21, 0.50]). Red flag score was not significantly different among Year 11 pupils, after being referred via the DHC in Year 9 (-0.36 red flags [95% CI -0.97, 0.24]).

Discussion

The DHC, and similar screening tools, have the potential to raise awareness of the health and wellbeing support in schools and provide an additional pathway of referral to this support for pupils with unmet health needs, without replacing the traditional pathway where pupils refer themselves or are referred by teachers.

The location of an internal focus of attention differentially affects motor performance

by Andrew J. Strick, Logan T. Markwell, Hubert Makaruk, Jared M. Porter

Prior research has questioned the appropriateness of internal focus instructions or the juxtaposition to external and control conditions. Moreover, there has been a lack of research conducted to test a variety of internal conditions on motor performance. The purpose of the present study was to address those critiques and add to the attentional focus literature by varying the location of an internal focus while performing a standing long jump. Participants performed a standing long jump during five separate conditions (internal focus: toes, knees, hips, arms; and control). The analysis revealed that all internal focus conditions performed worse than the control condition. Furthermore, the only difference between internal conditions was found between arms and knees, where the knee condition resulted in a significantly shorter jump distance relative to the arms. Regardless of the location specified, all internal focus conditions led to detriments in jump performance when compared to the control condition. These findings add to a large body of work demonstrating the importance of instructional content on motor performance.