Articles: hyperalgesia.
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To determine whether initial nociceptive inputs caused by subcutaneous injection of formalin into the hindpaw are necessary and/or sufficient for allodynic behavior and microglial activation observed at one week following behavior, we examined Sprague-Dawley rats under five test conditions. Test condition 1. Formalin alone group (six rats), 5% formalin was injected subcutaneously into the dorsal side of the right hind paw. ⋯ The lumbar spinal cord was immunohistochemically processed at one week to assess the expression of a marker for activated microglia. The results showed: (i) pre-treatment with bupivacaine blocked both phases of formalin-evoked pain behaviors and the mechanical allodynia that developed one week post-formalin injection, but did not block microglial activation; (ii) treatment with bupivacaine 1h after formalin injection reduced paw edema and prevented skin ulceration, but one week allodynia and microglial activation were still present; and (iii) prolonged spinal microglial activation was not dependent on acute formalin-induced nociceptor activity, but was strongly associated with the amount of tissue destruction. Our studies suggest that: (i) the central sensitization associated with the phase II of formalin-evoked behaviors and spinal microglial activation are both necessary to permit the development of the long-term hyperalgesia produced by the subcutaneous administration of formalin into the rat's hindpaw; and (ii) acute nociceptive inputs following formalin injection are not necessary for central microglial activation that may be triggered by nerve damage or prolonged signals from peripherally inflamed tissue
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Previous studies have shown that transection of the sciatic nerve induces dramatic changes in sodium currents of axotomized dorsal root ganglion (DRG) neurons, which are paralleled by significant changes in the levels of transcripts of several sodium channels expressed in these neurons. Sodium currents that are resistant to tetrodotoxin (TTX-R) and the transcripts of two TTX-R sodium channels are significantly attenuated, while a rapidly repriming tetrodotoxin-sensitive (TTX-S) current emerges and the transcripts of alpha-III sodium channel, which produce a TTX-S current when expressed in oocytes, are up-regulated. ⋯ Transcripts of NaN and SNS, two sensory neuron-specific TTX-R sodium channels, are significantly down-regulated as is the TTX-R sodium current, while transcripts of the TTX-S alpha-III sodium channel and a rapidly repriming TTX-S Na current are up-regulated in small diameter DRG neurons. These changes may provide at least a partial basis for the hyperexcitablity of DRG neurons that contributes to hyperalgesia in this model.
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Anesthesia and analgesia · Dec 1999
Randomized Controlled Trial Clinical TrialThe effects of intradermal fentanyl and ketamine on capsaicin-induced secondary hyperalgesia and flare reaction.
In this study, we evaluated the effects of intradermal fentanyl and ketamine on capsaicin-induced hyperalgesia and axon-reflex flare. In addition, we obtained dose-response curves for possible local anesthetic effects. Saline (200 microL) and either fentanyl (1 microg or 10 microg in 200 microL) or ketamine (100 microg or 1000 microg in 200 microL) were injected simultaneously into the central volar forearm of 12 healthy volunteers. Nine minutes later, capsaicin (10 microg in 20 microL) was injected intracutaneously exactly between the two injection sites. Areas of touch-evoked allodynia and pinprick hyperalgesia, as well as intensity of pinprick hyperalgesia at the injection sites and axon-reflex flare, were evaluated. Fentanyl did not affect the area or intensity of secondary hyperalgesia. Only the larger concentration of fentanyl locally diminished axon-reflex flare without affecting mechanical detection thresholds. Inhibitory effects of ketamine on intensity of secondary hyperalgesia and axon reflex flare were observed only in the larger concentration. However, this concentration also clearly elevated mechanical detection thresholds. No inhibitory effects of ketamine in the smaller concentrations were observed. We conclude that fentanyl inhibits neuropeptide release on peripheral application without modulating secondary hyperalgesia. Ketamine failed to inhibit both secondary hyperalgesia and axon reflex flare as long as nonlocal anesthetic concentrations were applied. ⋯ We investigated the peripheral effects of fentanyl and ketamine on capsaicin-induced hyperalgesia and axon-reflex flare. In large concentrations, the opioid diminished axon-reflex flare without effects on secondary hyperalgesia. We found no evidence for the involvement of endogenous glutamate in secondary hyperalgesia or axon reflex flare.