Variation of pain and vasomotor responses evoked by intramuscular infusion of hypertonic saline in human subjects: influence of gender and its potential neural mechanisms.

The aim of current study was to explore role of gender in pain and cutaneous vasomotor responses during the condition of intramuscular (i.m.) hypertonic (HT, 5.8%) saline induced muscle pain. In 20 healthy human subjects (10 females), 2-4.8ml of either HT or isotonic (IT, 0.9%) saline was infused into the left tibialis anterior muscle to elicit muscle pain, during which the intensity and distribution of pain together with skin vasomotor responses were investigated. Cutaneous blood flow was assessed using laser-Doppler flowmetry in 4 different skin areas: ipsilateral infusion area (5cm×5cm), ipsilateral referred pain area (5cm×10cm), contralateral area to the infusion site (5cm×5cm), and contralateral area to the referred pain site (5cm×10cm). Among the different i.m. infusions, 4.8ml HT saline evoked the highest pain intensity, the longest pain duration, and the largest pain distribution area in different subjects (P<0.001). Gender-related differences in pain and skin vasomotor responses were observed following the i.m. HT, but not IT, saline infusion while women exhibited stronger pain intensity and duration (P<0.001), and more expressed vasomotor responses (P<0.05) at the infusion area and contralateral mirror site. Intramuscularly pre-treating the infusion area with 1ml of 2% lidocaine markedly reduced the muscle pain and blocked the increased skin blood flow in both men and women (P<0.05). However, post-treatment with lidocaine significantly reduced the pain intensity and the increased skin blood flow only in men, but not women. The data demonstrate that gender-associated difference exists in HT saline intramuscularly induced local muscle pain and vasomotor responses. Neural mechanisms underlying gender-related differences in vasomotor responses is significantly different, suggesting that local pre-treatment, but not post-treatment, with anesthetic may provide superior analgesia to block sex-associated difference in pain and vasomotor responses.