Hindlimb flexion withdrawal evoked by noxious heat in conscious rats: magnitude measurement of stimulus-response function, suppression by morphine and habituation

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Abstract
1. The aim of this study was to develop a quantitative behavioral model of nociception. Electromyographic (EMG) recordings from a hamstring flexor muscle provided a measure of the magnitude of hindlimb withdrawals elicited by brief, graded noxious contact thermal stimuli applied to the hindpaw in conscious rats. 2. The magnitude of limb withdrawals showed a significant, usually linear, increase with stimulus temperature from a threshold of approximately 40 up to 52 degrees C. Stimulus-response functions of withdrawal magnitude versus temperature were reproducible within and across rats. Withdrawal magnitude was much more tightly correlated with stimulus temperature (r2 = 0.76, 0.73) than was withdrawal latency (r2 = 0.57, 0.55). 3. Systemic administration of the opiate analgesic morphine (3.5 mg/kg ip) suppressed withdrawals in a naloxone-reversible manner, such that the slope of the stimulus-response function was significantly reduced without an increase in threshold. 4. Successive withdrawals to repeated, identical noxious heat stimuli decreased in a manner consistent with habituation. The response recovered to the prehabituated level after a 15-min rest period, and subsequently decremented even more quickly. The decrement in withdrawal magnitude was greater at lower stimulus intensities and shorter interstimulus intervals, and transferred to a nearby (7.5 mm) but not distant (2.5 cm) site. Evidence for dishabituation was also obtained. 5. The advantages of this method as an animal model of nociception are presented and discussed in terms of the underlying neural circuitry and its modulation.

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