Pain on i.v. injection of some anaesthetic agents is evoked by the unphysiological osmolality or pH of their formulations.

We have studied the intensity and time-course of pain during and after injection into an isolated vein segment in seven normal subjects of saline or glucose of different osmolalities (0-6 osmol kg-1) or pH (2-13). Pain scores were recorded continuously by a modified visual analogue scale apparatus. With osmolar stimulation, pain occurred at 1.0 osmol kg-1 during perfusion and 3.0 osmol kg-1 with rapid injection and increased with osmolar concentration of both saline and glucose solutions. Acidic and alkaline solutions evoked pain at a pH value less than 4 or greater than 11. We conclude that pain on i.v. injection of some sedative and hypnotic drugs is likely to be caused by formulations of extremely unphysiological osmolalities or pH values.