Characterization of a method for measuring primary hyperalgesia of deep somatic tissue

Measuring primary hyperalgesia from deep somatic tissue (ie, muscle and joint) is difficult in laboratory animals but clinically important. In this study, we modified a newly developed method to measure primary hyperalgesia of muscle in rats and compared this with primary hyperalgesia from the knee. Compression withdrawal thresholds of the gastrocnemius muscle or the knee joint were measured with a device consisting of strain gauges attached to forceps. Compression of the muscle or joint with the forceps results in hind limb withdrawal, and thresholds were measured before and 4 hours after induction of inflammation by 3% carrageenan injected into the gastrocnemius muscle or 3% kaolin-carrageenan injected into the knee joint. Compression thresholds were significantly decreased 4 hours after induction of inflammation in the muscle or knee joint compared with thresholds before inflammation. Surprisingly, in animals with muscle inflammation, compression thresholds were also significantly decreased on the contralateral hind limb. Systemic morphine (5 mg/kg, intraperitoneal) or lidocaine (2%) injected into the inflamed tissue reversed the decreased compression threshold induced by deep tissue inflammation. However, local anesthetic applied to the skin overlying the muscle or knee joint did not affect the decreased threshold. Thus, we report a consistent and convenient method to measure primary hyperalgesia in deep tissues of rats. The measured hyperalgesia originates in the inflamed tissues and has no measurable contribution from skin.

The current method measures primary hyperalgesia directly from injured deep somatic tissues. Thus it is relevant to painful clinical conditions that are aggravated by mechanical pressure at the site of injury. As such, it might serve as a model for basic mechanistic studies as well as drug discovery for musculoskeletal pain syndromes.