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Thermal sensitivity is an essential characteristic of some painful states, including oxaliplatin-induced neuropathy. The thermal place preference test (TPPT) was designed to finely assess thermal sensitivity in rodents. The TPPT monitors the time spent by unrestrained rodents on a test plate at fixed temperatures (5-50°C) compared with an adjacent reference plate at a neutral temperature (25°C). Here, we report the results of a study designed (i) to validate the optimal methodological parameters for measuring thermal sensitivity in rats, (ii) to assess the thermal sensitivity of healthy rats and animal models of pain and (iii) to explore the pharmacological effects of analgesic drugs. The most reproducible conditions occurred when the TPPT was performed in the morning and in the dark for 3 min with the reference plate set to 25°C. The temperature preferences of healthy rats were more than 17°C and less than 40°C. When compared with control animals, oxaliplatin-treated rats showed thermal hypersensitivity at 12, 20 and 35°C, and carrageenan-treated rats showed thermal hypersensitivity at 15 and 45°C. Duloxetine (2.5 mg/kg, intraperitoneal) reversed oxaliplatin-induced cold hypersensitivity (20°C) and morphine (1 mg/kg, intravenous) reversed carrageenan-induced heat hypersensitivity (45°C). We conclude that the TPPT enables a fine-grained assessment of thermal sensitivity that is relevant to the pathophysiological exploration of animal pain models and to the pharmacological assessment of analgesic drugs.

We describe an animal model of nociceptive sensory neuropathy induced by repeat intravenous administration of oxaliplatin in which treated animals partly reproduce the characteristic pain symptoms in oxaliplatin-treated patients. We tested the ability of 1, 2 and 4 mg/kg oxaliplatin doses injected twice-weekly for four-and-a-half consecutive weeks to induce a nociceptive peripheral neuropathy in male Sprague-Dawley rats. The behavioral assessment revealed cold allodynia (10 degrees C) and hyperalgesia (4 degrees C) symptoms associated with a mechanical allodynia. The rats maintained a good general clinical status without motor dysfunction. The 2mg/kg oxaliplatin dose and the tail-immersion test in cold water (10 degrees C) were selected to compare pharmacological sensitivity between single administered drugs as morphine, lidocaine, carbamazepine, gabapentin and repeated administration of drugs as clomipramine, venlafaxine, calcium and magnesium solutions. Magnesium solution (90 mg/kg) and venlafaxine (7.5 mg/kg) administration induced an antinociceptive effect whereas gabapentin (300 mg/kg), clomipramine (2.5 mg/kg) and lidocaine (3 and 6 mg/kg) only induced an antiallodynic effect.

Acrylamide was intraperitoneally administered to male Sprague-Dawley rats at four different doses (5, 10, 20 and 30 mg/kg) three times a week for 5 consecutive weeks. Because of motor dysfunction, the 30 mg/kg dose was not used for behavioral pain tests. Clinical status remained good throughout the experiment and no motor deficit was observed at the other doses. We showed that acrylamide administration at low doses and cumulative dose (CD) range of 35-140 mg/kg produced mechanical allodynia and rapid, marked heat (42 degrees C) and cold (10 degrees C) allodynia after tail immersion test. Mechanical and thermal hyperalgesia appeared after higher cumulative doses (70-280 mg/kg), except for cold (4 degrees C) hyperalgesia (20-80 mg/kg). All the modifications persisted throughout all study, except the mechanical hyperalgia. All the cumulative doses tested were lower than those generally reported to induce motor dysfunction (CD250 mg/kg), confirming that CD may be considered to be a suitable index in assessing neurological signs and suggesting that early detection of acrylamide neurotoxicity would be possible using the sensory tests, especially those for detecting allodynia thresholds.