Quantification of local and referred muscle pain in humans after sequential i.m. injections of hypertonic saline

Abstract
The aim of the present study was to test (1) whether muscle pain is influenced by temporal and spatial summation, and (2) whether sequential noxious muscle stimuli applied at hourly interstimulus-intervals could produce an increased sensation of pain due to central hyperexcitability. In the study eleven healthy men were exposed to computer-controlled intramuscular infusion of saline (5%) given over 20 s in m. tibialis anterior (m. TA). The intensities of local and referred pain were assessed by recordings on visual analogue scales (VAS), and the areas of local pain (around the injection site) and referred pain (outside the local pain area) were localised by the subject. Three experiments were performed. Experiment 1: Each subject participated in three tests separated by one week: (a) bolus (0.4 ml saline) infusion at one site; (b) four sequential infusions (0.1 ml saline) given at 90-s interstimulus-intervals at one site; and (c) four sequential infusions (0.1 ml saline) given at 360-s interstimulus-intervals at one site. Experiment 2: This was performed as experiment 1, but the infusions were given at spatially separated sites. Experiment 3. Hypertonic saline (0.1 ml) was injected one, four and 24 h after the sequential infusions (90-s interstimulus-intervals) given at spatially separated sites. The highest VAS peak and the largest local and referred pain areas were found after the bolus infusions. Compared to the first infusion, significant increases were found in the VAS peak, the size of the local pain area, and the size of the referred pain area (non-significant) after the four sequential infusions given at 90-s interstimulus-intervals (temporal summation). Four spatially separated infusions given simultaneously produced a higher VAS peak, a larger local pain area, and a larger referred pain area (non-significant) compared to one infusion (spatial summation). The infusion given 4 h after the sequential infusions tended to produce an increase in the referred pain area and in the pain intensity. In all three experiments significant correlations were found between the VAS peak and the size of the local (R = 0.64, P < 0.0001, n = 231) and referred (R = 0.47, P < 0.0001, n = 231) pain areas. Based on the above results it can be concluded that experimental muscle pain is influenced by temporal and spatial summation.