Pain caused by
subcutaneous injections is unpleasant, which may limit patient compliance. The objective of this study was to use spinal reflexes to quantify
subcutaneous injection pain. Spinal reflexes were measured using an electromyogram (EMG) test. The effects of injection volume, pH and osmotic pressure were investigated. The EMG responses increased with injection volume and the acidity of the
solution but did not depend on the osmotic pressure of the
solution. The EMG responses differed for subcutaneously injected
sodium chloride and
glucose over the same range of osmotic pressures.
Pain caused by the
subcutaneous injections was unrelated to the osmotic ratio up to approximately 5. The injection
pain caused by therapeutic
protein solutions was also evaluated. We compared the EMG responses of the
adalimumab and
etanercept, as the injection of
adalimumab is more painful than that of
etanercept in humans. The EMG magnitude for
adalimumab was twice that induced by
etanercept as observed for the EMG tests performed in rats. Therapeutic
proteins account for an increasingly large proportion of
pharmaceutical drugs. When a high dose of therapeutic
proteins is required, the
protein solution must often be highly concentrated to reduce the injection volume. For patient comfort, it is critical to reduce injection
pain. The EMG test reported here allows
subcutaneous injection pain to be quantified and may be useful for optimizing
drug formulations.