Estimating Efficacy and Drug ED50's Using von Frey Thresholds: Impact of Weber's Law and Log Transformation

Mills, Charles D.; LeBlond, David; Joshi, Sunil Kumar; Zhu, Chang; Hsieh, Gin C.; Jacobson, Peer B.; Meyer, Michael D.; Decker, Michael

doi:10.1016/j.jpain.2012.02.009

Cited by 103 publications

(90 citation statements)

References 5 publications

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“…To meet the assumption of normality of our dependent variable (50% PWT), we Log 10 transformed the 50% PWT values (Mills et al, 2012). We used IBM SPSS Statistics 20 to analyze the data.…”

Section: Methodsmentioning

confidence: 99%

Recovery Sleep Does Not Mitigate the Effects of Prior Sleep Loss on Paclitaxel-Induced Mechanical Hypersensitivity in Sprague-Dawley Rats

Kozachik

Opp

Page

2014

Biological Research For Nursing

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Society has a rapidly growing accumulative sleep debt due to employment obligations and lifestyle choices that limit sleep opportunities. The degree to which poor sleep may set the stage for adverse symptom outcomes among more than 1.7 million persons who will be diagnosed with cancer is not entirely understood. Paclitaxel (PAC), a commonly used chemotherapy agent, is associated with painful, debilitating peripheral neuropathy of the hands and feet, which may persist long after adjuvant therapy is completed. The aims of this preclinical study were to determine the accumulative and sustained effects of sleep restriction on PAC-induced mechanical sensitivity in animals and whether there are male–female differences in mechanical sensitivity in PAC-injected animals. Sixty-two adult Sprague-Dawley rats (n = 31 females) were assigned to three cycles of intraperitoneal injections of PAC (1 mg/kg) versus vehicle (VEH; 1 ml/kg) every other day at light onset for 7 days, followed by seven drug-free days and to sleep restriction versus unperturbed sleep. Sleep restriction involved gentle handling to maintain wakefulness during the first 6 hr of lights on immediately following an injection; otherwise, sleep was unperturbed. Mechanical sensitivity was assessed via von Frey filaments, using the up–down method. Mechanical sensitivity data were Log10 transformed to meet the assumption of normality for repeated measures analysis of variance. Chronic sleep restriction of the PAC-injected animals resulted in significantly increased mechanical sensitivity that progressively worsened despite sleep recovery opportunities. If these relationships hold in humans, targeted sleep interventions employed during a PAC protocol may improve pain outcomes.

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“…To meet the assumption of normality of our dependent variable (50% PWT), we Log 10 transformed the 50% PWT values (Mills et al, 2012). We used IBM SPSS Statistics 20 to analyze the data.…”

Section: Methodsmentioning

confidence: 99%

Recovery Sleep Does Not Mitigate the Effects of Prior Sleep Loss on Paclitaxel-Induced Mechanical Hypersensitivity in Sprague-Dawley Rats

Kozachik

Opp

Page

2014

Biological Research For Nursing

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“…Please note that, as in our previous paper (67), we logged the data of the behavioural testes to ensure a normal distribution since the Von Frey's hairs are distributed on an exponential scale. Mills et al, 2012, recently demonstrated that Log transformation makes more 'mathematical and biological sense' (62).…”

Section: Immunohistochemistrymentioning

confidence: 99%

Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice

et al. 2018

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Overline: PainOne Sentence Summary: Silencing key neurons with botulinum toxin conjugates exerts long-lasting pain relief in mouse models of chronic pain. 2 AbstractChronic pain is a widespread debilitating condition affecting millions of people worldwide. Although several pharmacological treatments for relieving chronic pain have been developed, they require frequent chronic administration and are often associated with severe adverse events, including overdose and addiction. Persistent increased sensitization of neuronal subpopulations of the peripheral and central nervous system has been recognized as a central mechanism mediating chronic pain, suggesting that inhibition of specific neuronal subpopulations might produce antinociceptive effects. We leveraged the neurotoxic properties of the botulinum toxin to specifically silence key pain processing neurons in the spinal cords of mice.We show that a single intrathecal injection of botulinum toxin conjugates produced long-lasting pain relief in mouse models of inflammatory and neuropathic pain without toxic side effects. Our results suggest that this strategy might be a safe and effective approach for relieving chronic pain while avoiding the adverse events associated with repeated chronic drug administration.

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“…Because a number of our dependent variables were not normally distributed, we log 10 transformed the 50% PWT values that we obtained via VFH testing as well as the baseline and post-EPM corticosterone levels (Mills et al, 2012). We used IBM SPSS Statistics 20 to analyze the data.…”

Section: Methodsmentioning

confidence: 99%

A Hyperresponsive HPA Axis May Confer Resilience Against Persistent Paclitaxel-Induced Mechanical Hypersensitivity

Kozachik

Page

2015

Biological Research For Nursing

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Paclitaxel (PAC) treatment is associated with persistent, debilitating neuropathic pain that affects the hands and feet. Female sex and biological stress responsivity are risk factors for persistent pain, but it is unclear whether these important biologically based factors confer risk for PACinduced neuropathic pain. To determine the relative contributions of sex and hypothalamicpituitary-adrenal (HPA)-axis stress responsivity to PAC-induced mechanical hypersensitivity, we employed a PAC protocol consisting of three, 2-week cycles of every-other-day doses of PAC 1 mg/kg versus saline (Week 1) and recovery (Week 2), totaling 42 days, in mature male and female Fischer 344, Lewis, and Sprague Dawley (SD) rats, known to differ in HPA axis stress responsivity. Mechanical sensitivity was operationalized using von Frey filaments, per the updown method. Among PAC-injected rats, SD rats exhibited significantly greater mechanical hypersensitivity relative to accumulative PAC doses compared to Fischer 344 rats. Lewis rats were not significantly different in mechanical hypersensitivity from SD or Fischer 344 rats. At the end of the protocol, PAC-injected SD rats exhibited profound mechanical hypersensitivity, whereas the PAC-injected Fischer 344 rats appeared relatively resilient to the long-term effects of PAC and exhibited mechanical sensitivity that was not statistically different from their saline-injected counterparts. Sex differences were mixed and noted only early in the PAC protocol. Moderate HPA axis stress responsivity may confer additional risk for the painful effects of PAC. If these findings hold in humans, clinicians may be better able to identify persons who may be at increased risks for developing neuropathic pain during PAC therapy. KeywordsFischer 344; Sprague Dawley; Lewis; rats; neuropathic pain Reprints and permission: sagepub.com/journalsPermissions.nav Corresponding Author: Sharon L. Kozachik, PhD, RN, School of Nursing, Johns Hopkins University, 525 North Wolfe Street, Room 445, Baltimore, MD 21205, USA. skozach1@jhu.edu. Authors' NoteThe content is solely the responsibility of the authors and does not necessarily represent the official views of the Oncology Nursing Society Foundation, of the National Institute of Nursing Research, or of the National Institutes of Health.Author Contribution SLK contributed to conception and design; acquisition, analysis, and interpretation; drafted the manuscript; critically revised the manuscript; gave final approval; and agrees to be accountable for all aspects of work ensuring integrity and accuracy. GGP contributed to design; acquisition and interpretation; critically revised the manuscript; gave final approval; and agrees to be accountable for all aspects of work ensuring integrity and accuracy. Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscrip...

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Estimating Efficacy and Drug ED50's Using von Frey Thresholds: Impact of Weber's Law and Log Transformation

Cited by 103 publications

References 5 publications

Recovery Sleep Does Not Mitigate the Effects of Prior Sleep Loss on Paclitaxel-Induced Mechanical Hypersensitivity in Sprague-Dawley Rats

Recovery Sleep Does Not Mitigate the Effects of Prior Sleep Loss on Paclitaxel-Induced Mechanical Hypersensitivity in Sprague-Dawley Rats

Selective neuronal silencing using synthetic botulinum molecules alleviates chronic pain in mice

A Hyperresponsive HPA Axis May Confer Resilience Against Persistent Paclitaxel-Induced Mechanical Hypersensitivity

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