Pain
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Enadoline is a highly selective and potent kappa-opioid receptor agonist. This report describes and compares the activities of enadoline and morphine in a rat model of postoperative pain. A 1 cm incision through the muscle and skin of the plantar surface of the right hind paw induced thermal hyperalgesia as well as static and dynamic allodynia lasting at least 2 days. ⋯ Morphine dose-dependently (1-6 mg/kg, s.c.) potentiated isoflurane-induced sleeping time and respiratory depression in the rat. However, whilst enadoline also (1-1000 microg/kg, i.v.) potentiated isoflurane-induced sleeping time, it did not cause respiratory depression. It is suggested that enadoline may possess therapeutic potential as a pre-emptive antihyperalgesic and antiallodynic agent.
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We studied the effect of unilateral ligation of two spinal nerves on behavioral pain responses evoked by various types of cutaneous stimuli in the adult rat. Furthermore, we determined the effect of spinal nerve ligation on morphology of the peripheral nerves. The most consistent behavioral finding (83%) was a marked decrease in monofilament-induced hindlimb withdrawal thresholds (mechanical allodynia) ipsilateral to the spinal nerve ligation. ⋯ However, this mechanical allodynia may differentially dissociate from mechanical and thermal hyperalgesia at various post-operative time points. The marked mechanical allodynia together with a dramatic decrease in the number of myelinated nerve fibers is paradoxical, since the activation of myelinated nerve fibers by monofilaments produced abnormally strong behavioral responses. This paradox may be explained by spinal nerve ligation-induced amplification or disinhibition of tactile signals at central levels.