The use of rat spinal reflexes to quantify injection pain

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.

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