Pain
-
N-methyl-D-aspartate (NMDA) receptors serve prominent roles in vast physio-pathological conditions including hyperalgesia (defined as augmented pain intensity in response to painful stimuli) associated with central sensitization. Using M40403 a synthetic low molecular weight superoxide dismutase mimetic that removes superoxide we show for the first time that this radical plays a key role in NMDA-mediated hyperalgesia. Intrathecal administration of NMDA in rats led to a time-dependent development of thermal hyperalgesia. ⋯ M40403 by preventing MnSOD nitration restored its activity and inhibited the hyperalgesic response to intrathecal NMDA. Thus, superoxide-mediated nitration and deactivation of spinal MnSOD is a novel pathway of NMDA-mediated spinal hyperalgesia and hence central sensitization since it helps to maintain high levels of superoxide that in turn maintains nociceptive signaling. The broader implication of our findings is that superoxide may contribute to various forms of pain events that are driven by NMDA-receptor activation.
-
Chemical cauterization of the central cornea with silver nitrate was assessed as a superficial injury model of tissue sensitization accompanying acute inflammation. Adult male Sprague-Dawley rats were anesthetized with halothane gas, and the centers of their right corneas treated with a silver nitrate applicator stick (75% silver nitrate, 25% potassium nitrate) to produce a discrete lesion 1 mm in diameter. Edema of the corneal stroma and elevated immune cell counts became significant 4 h after cauterization, and were still evident after 48 h. ⋯ A significant increase in stimulus-induced blinking was evident 2 h after cauterization. Chemical sensitization peaked at 6 h, and was no longer significant at 12 h. We conclude that silver nitrate cauterization produces acute corneal inflammation and hyperalgesia, and may prove a useful model for the study of primary afferent nociceptors.
-
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. ⋯ 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 (CD>250 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.