Clinical neuroscienceDemarcation of secondary hyperalgesia zones: Punctate stimulation pressure matters

- Secondary hyperalgesia area is a primary outcome in studies of analgesic efficacy.
- The literature indicates a lack of standardization in demarcation paradigms.
- Standardized demarcation of areas were made with different punctate stimulators.
- A highly significant correlation between applied pressure and area was demonstrated.
- Standardized assessment methods are recommended in future research.

BackgroundSecondary hyperalgesia is increased sensitivity in normal tissue near an injury, and it is a measure of central sensitization reflecting injury-related effects on the CNS. Secondary hyperalgesia areas (SHAs), usually assessed by polyamide monofilaments, are important outcomes in studies of analgesic drug effects in humans. However, since the methods applied in demarcating the secondary hyperalgesia zone seem inconsistent across studies, we examined the effect of a standardized approach upon the measurement of SHA following a first degree burn injury (BI).New methodThe study was a two-observer, test-retest study with the two sessions separated by 6 wk. An observer-blinded design adjusted to examine day-to-day and observer-to-observer variability in SHA was used. In 23 healthy volunteers (12 females/11 males) a BI was induced by a contact thermode (47.0 °C, 420 s, 2.5 × 5.0 cm2). The SHA, demarcated by polyamide monofilaments (bending force: 0.2, 69 and 2569 mN) and a “weighted-pin” stimulator (512 mN), were assessed 45 to 75 min after each BI.ResultsA random effect, linear mixed model demonstrated a logarithmic correlation between elicited skin pressures (mN/mm2) and the SHAs (P < 0.0001). No day-to-day or observer-to-observer differences in SHAs were observed. Intraclass correlation coefficients, in the range of 0.51 to 0.84, indicated a moderate to almost perfect reliability between observers.Comparison with existing methodsNo standardized approach in SHA-assessment has hitherto been presented.ConclusionsThis is the first study to demonstrate that demarcation of secondary hyperalgesia zones depends on the developed pressure of the punctate stimulator used.