Brain research
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Hyperalgesia following chronic morphine treatment is thought to be a response to opioid receptor activation and analgesia and contribute to the development of analgesic tolerance. Here, the relationship between these variables was studied in mice tested for nociceptive sensitivity on the tail-withdrawal test during chronic infusion of various morphine doses. Hyperalgesic onset was preceded by dose-dependent analgesia except for the lowest morphine dose, which caused hyperalgesia 6 h after the start of infusion. ⋯ In addition, acute injection of morphine-3beta-glucoronide (M3G) caused hyperalgesia that was cross-adaptive with the lower morphine dose only. The data demonstrate that morphine hyperalgesia is independent of prior or concurrent opioid receptor activity or analgesia and is unrelated to analgesic tolerance. Furthermore, the lack of hyperalgesic cross-adaptation between high and low morphine doses, and their differential cross-adaptation with M3G hyperalgesia, also suggests distinct morphine dose-dependent hyperalgesic systems.
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Comparative Study
Activation of p38 mitogen-activated protein kinase in spinal microglia mediates morphine antinociceptive tolerance.
Compelling evidence has suggested that spinal glial cells were activated by chronic morphine treatment and involved in the development of morphine tolerance. However, the mechanisms of glial activation were still largely unknown in morphine tolerance. In present study, we investigated the role of p38 mitogen-activated protein kinase (p38 MAPK) in the spinal cord in the development of chronic morphine antinociceptive tolerance. ⋯ Taken together, these findings suggested that p38 MAPK activation in the spinal microglia was involved in the development of morphine antinociceptive tolerance. Inhibition of p38 MAPK by SB203580 in the spinal cord attenuated but not reversed the tolerance to morphine analgesia. The present study provides the first evidence that p38 activation in spinal microglia played an important role in the development of tolerance to morphine analgesia.
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Our previous study has proven that hypothalamic paraventricular nucleus (PVN) played a role in the antinociception. The central bioactive substances involving in the PVN regulating antinociception were investigated in the rat. ⋯ There was a negative relationship between the PVN AVP concentration and the pain threshold; pain stimulation enhanced the AVP, not OXT mRNA expression in the PVN using in situ hybridization and RT-PCR; intraventricular injection of anti-AVP serum completely reversed L-glutamate sodium injection into the PVN-induced antinociception, and administration of naloxone - the opiate peptide antagonist, partly blocked this L-glutamate sodium effect, but anti-OXT serum pretreatment did not influence this L-glutamate sodium effect; L-glutamate sodium injection into the PVN-induced analgesia was inhibited by V2 receptor antagonist - d(CH2)5[D-Ile2, Ile4, Ala-NH2(9)]AVP, not V1 receptor antagonist - d(CH2)5Tyr(Me)AVP. The data suggested that the PVN was limited to the central AVP, not OXT, which was through V2, not V1 receptors influencing the endogenous opiate peptide system, to regulate antinociception.
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Clinical Trial
Affective modulation of somatosensory-evoked potentials elicited by tactile stimulation.
The present investigation was aimed to evaluate the influence of emotional valence on brain correlates of non-painful somatosensory processing. For this purpose, we examined changes on the somatosensory-evoked potentials (SEP) elicited by frequent and deviant tactile stimuli (probability 14%) when subjects were viewing affective pictures. Twenty healthy volunteers aged between 19 and 47 years old participated in the study. ⋯ Furthermore, larger SEP amplitudes were obtained in response to the deviant than to the frequent stimuli. In addition, unpleasant pictures elicited larger P200 amplitudes of the VEP than pleasant. Data suggest that affective stimuli may modulate the early processing of somatosensory information in the brain, probably reflecting the existence of an adaptive perceptual/attentional mechanism to motivationally relevant stimuli.