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A modified Hargreaves' method for assessing threshold temperatures for heat nociception.

ABSTRACT: This study describes a modified Hargreaves' method for assessing paw withdrawal threshold temperatures for heat (PWT-H) nociception in the hind paws of rats. This method utilises radiant heat to maintain controlled lamp temperatures (CLTs) on a glass floor beneath the rat hind paw. An ascending series of CLTs were applied for 10s, with 5-10min intervals between applications, until characteristic withdrawal behaviour was observed or a cutoff CLT was reached. The average plantar epicutaneous temperatures measured from anaesthetised rats corresponding to CLTs and withdrawal latencies were used for determining PWT-H. The mean PWT-H in 2-month-old (mo) naïve Sprague-Dawley rats (n=38) was 47.6±0.2°C, which is comparable to the noxious threshold temperature for human glabrous skin (46.5±0.5°C). The PWT-H was consistent between trials and daily assessments over four consecutive days. No significant differences were observed between the PWT-H in 2-, 6- to 8-, and >24-mo F344 rats, but the PWT-H in 1-mo rats was significantly reduced. Three hours following plantar incision, the PWT-H decreased to 37.5±0.2°C, consistent with previous observations of C-fibre afferents from incised glabrous skin firing at 36.7±3.6°C. Parallel testing, using the current method and an electronic von Frey device, illustrated similar degrees of incision-induced hyperalgesia, gradual improvements in hyperalgesia, and reversals induced through morphine and gabapentin. In conclusion, the present method facilitates a comparison of PWT-H using electrophysiological and human psychophysical studies involving thermosensation, and as a behavioural assay identical to von Frey testing, this method also measures the threshold for nociception.

SUBMITTER: Banik RK

PROVIDER: S-EPMC3759573 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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A modified Hargreaves' method for assessing threshold temperatures for heat nociception.

Banik Ratan K RK Kabadi Rajiv A RA

Journal of neuroscience methods 20130622 1

This study describes a modified Hargreaves' method for assessing paw withdrawal threshold temperatures for heat (PWT-H) nociception in the hind paws of rats. This method utilises radiant heat to maintain controlled lamp temperatures (CLTs) on a glass floor beneath the rat hind paw. An ascending series of CLTs were applied for 10s, with 5-10min intervals between applications, until characteristic withdrawal behaviour was observed or a cutoff CLT was reached. The average plantar epicutaneous tempe ...[more]

PMID: 23796910

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Project description:BackgroundImmunological correlates of protection are biological markers such as disease-specific antibodies which correlate with protection against disease and which are measurable with immunological assays. It is common in vaccine research and in setting immunization policy to rely on threshold values for the correlate where the accepted threshold differentiates between individuals who are considered to be protected against disease and those who are susceptible. Examples where thresholds are used include development of a new generation 13-valent pneumococcal conjugate vaccine which was required in clinical trials to meet accepted thresholds for the older 7-valent vaccine, and public health decision making on vaccination policy based on long-term maintenance of protective thresholds for Hepatitis A, rubella, measles, Japanese encephalitis and others. Despite widespread use of such thresholds in vaccine policy and research, few statistical approaches have been formally developed which specifically incorporate a threshold parameter in order to estimate the value of the protective threshold from data.MethodsWe propose a 3-parameter statistical model called the a:b model which incorporates parameters for a threshold and constant but different infection probabilities below and above the threshold estimated using profile likelihood or least squares methods. Evaluation of the estimated threshold can be performed by a significance test for the existence of a threshold using a modified likelihood ratio test which follows a chi-squared distribution with 3 degrees of freedom, and confidence intervals for the threshold can be obtained by bootstrapping. The model also permits assessment of relative risk of infection in patients achieving the threshold or not. Goodness-of-fit of the a:b model may be assessed using the Hosmer-Lemeshow approach. The model is applied to 15 datasets from published clinical trials on pertussis, respiratory syncytial virus and varicella.ResultsHighly significant thresholds with p-values less than 0.01 were found for 13 of the 15 datasets. Considerable variability was seen in the widths of confidence intervals. Relative risks indicated around 70% or better protection in 11 datasets and relevance of the estimated threshold to imply strong protection. Goodness-of-fit was generally acceptable.ConclusionsThe a:b model offers a formal statistical method of estimation of thresholds differentiating susceptible from protected individuals which has previously depended on putative statements based on visual inspection of data.

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A modified Hargreaves' method for assessing threshold temperatures for heat nociception.

Publications

A modified Hargreaves' method for assessing threshold temperatures for heat nociception.

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