Force of limb withdrawals elicited by graded noxious heat compared with other behavioral measures of carrageenan-induced hyperalgesia and allodynia

Abstract

We investigated if carrageenan-induced thermal hyperalgesia and mechanical allodynia are associated with a reduction in threshold and–or enhancement of suprathreshold nocifensive responses, using a method to measure the force of a hind limb withdrawal reflex elicited by graded noxious heat stimuli (36–52°C, 5 s) delivered by Peltier thermode tethered to the ventral hind paw of conscious rats. Withdrawal reflexes were recorded 2.5 h after intraplantar injection of carrageenan (1 or 0.1%) or saline vehicle in sessions >2 weeks apart: baseline reflexes were assessed the day before. Withdrawal reflex force increased linearly from 42–52°C. Carrageenan 1% significantly enhanced withdrawal reflexes at 40–46°C, reducing the slope and threshold of the stimulus-response function. This was associated with significant reductions in thermal paw withdrawal latency (Hargreaves test: by 50%), mechanical withdrawal threshold (by 82%) and weight bearing on the injected side (by 81%) measured with independent force plates. Smaller reductions in thermal paw withdrawal latency and mechanical withdrawal threshold, and smaller enhancement of withdrawal reflex force, were observed following 0.1% carrageenan. Intraplantar saline was ineffective. This method allows assessment of hyperalgesic changes in stimulus-response coding over a broad range of noxious stimulus intensities.