Determinants of thermal pain thresholds in normal subjects
Introduction
Pain evoked by normally innocuous thermal stimuli, referred to as heat and cold hyperalgesia, is an important symptom in neuropathic pain patients (Jensen and Baron, 2003). Quantitative measurements of thermal pain thresholds are therefore an essential part of quantitative sensory testing (QST) in clinical and research studies of pain.
QST results depend on subjective evaluation by the patient, i.e., it is a psychophysical method. Recently, Rolke et al. (Rolke et al., 2006) provided normal values from quantitative sensory testing of 180 healthy volunteers by the German Research Network on Neuropathic Pain. The data were obtained at 10 participating centers according to a standardized protocol and were proposed to serve as reference data for somatosensory testing in patients and clinical trials (Petersen and Rowbotham, 2006).
In that study, inter-individual variations in heat and cold pain thresholds resulted in very large 95% confidence intervals (Rolke et al., 2006). Therefore, low thermal pain thresholds (i.e., small differences in temperature from baseline) can lie within normal limits, e.g., a heat pain threshold of ⩾37 °C and a cold pain threshold of ⩽29 °C measured at the dorsum of the hands have to be considered normal.
As a consequence of the wide range of normal data for thermal pain thresholds, the temperature thresholds defining thermal hyperalgesia are very narrow, i.e., in the hand ranging from 32 to 37 °C for heat hyperalgesia and from 32 to 29 °C for cold hyperalgesia. It therefore seems likely that, in a number of patients presenting with symptoms of thermal hyperalgesia, sensitivity to heat and in particular cold determined using the thermotest device can provide false negative results when these control values are used as a reference.
One explanation for the low thermal pain thresholds in normal subjects may be their expectations. A lack of understanding of the range of temperatures to be experienced might induce avoidance behaviour triggered, e.g., by some fear of pain or of burns, so that the stop button is pressed before pain is actually perceived.
Another important aspect of thermal testing, which has not been investigated sufficiently, is the reproducibility of thermal pain threshold determinations. However, data on reliability are essential for long-term studies, like follow-up on natural history or therapy.
Finally, the normal protocol for testing thermal pain thresholds does not consider the nature of the perceptions induced by the changing temperature. However, knowledge of the qualitative ratings of perception at the threshold for pain might improve the sensitivity for evaluation of algesia via thermotesting (Kelly et al., 2005).
This study was aimed at devising methods to increase sensitivity and investigate reproducibility of quantitative thermotesting. Healthy subjects were tested to find out (a) whether a modified thermotest protocol incorporating the subject’s expectations is capable of changing the values determined for thermal pain thresholds, (b) how reproducible thermal pain thresholds are over a three-week period and (c) whether ratings of temperature and pain perception provide further useful information.
Section snippets
Subjects
Twenty healthy right-handed subjects were studied, divided into equal groups in which two different protocols for determining thermal thresholds were tested (protocol A: 5 women, 5 men, 36.7 ± 15.0 years [SD]; protocol B: 5 women, 5 men, 34.0 ± 9.4 years [SD]; no statistical difference between age of groups). All experiments were performed in a sitting position in a room held at a temperature of 22–23 °C and a relative humidity of 50–60%. By taking a medical history, we confirmed that all subjects
Influence of test protocol on thermal pain thresholds
Thermal pain thresholds were not influenced by the subjects’ being made familiar with the likely range of applied temperatures prior to the test. Both protocol A, adopted from the German Research Network on Neuropathic Pain, and the modified protocol B, in which the subjects were previously exposed to temperatures ranging from 10 to 40 °C, provided similar data with large inter-individual differences including low pain thresholds as previously published (Table 1) (Rolke et al., 2006). It is
Discussion
This study has demonstrated (a) that previous experience of test stimuli has no influence on the variability of thermal pain thresholds, (b) reproducibility of determinations of heat and cold pain thresholds within individuals and (c) the potential value of pain and temperature ratings at the thermal pain thresholds.
Conclusion
The results of this study indicate that modification of the investigation protocol to familiarize the subjects with the range of applied temperatures failed to reduce the wide range of normative data for thermal pain thresholds. Therefore, further approaches are needed to reduce the potential risk of false negative results in patients reporting thermal hyperalgesia. On the other hand, the reproducibility of thermal pain thresholds as well as pain and temperature ratings at the thresholds
Acknowledgements
We thank Elspeth McLachlan and Rob Boland for helpful discussion during the preparation of the manuscript. This work was supported by the Alexander von Humboldt-Foundation, the Spinal Injuries Research Centre (SIRC) at the Prince of Wales Medical Research Institute and the German Ministry of Research and Education within the German Research Network on Neuropathic Pain (BMBF, 01EM 05/04). J.A.B. is a research fellow of the National Health and Medical Research Council of Australia.
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