Articles: hyperalgesia.
-
Several investigators have coupled toxins to neuropeptides for the purpose of lesioning specific neurons in the central nervous system. By producing deficits in function these toxin conjugates have yielded valuable information about the role of these cells. In an effort to specifically stimulate cells rather than kill them we have conjugated the neuropeptide substance P to the catalytic subunit of cholera toxin (SP-CTA). This conjugate should be taken up selectively by neurokinin receptor expressing neurons resulting in enhanced adenylate cyclase activity and neuronal firing. ⋯ The finding that stimulation of adenylate cyclase in neurokinin receptor expressing neurons in the spinal cord produces thermal hyperalgesia is consistent with the known actions of these neurons. These data demonstrate that cholera toxin can be targeted to specific cell types by coupling the catalytic subunit to a peptide agonist for a g-protein coupled receptor. Furthermore, these results demonstrate that SP-CTA can be used as a tool to study sensitization of central neurons in vivo in the absence of an injury.
-
Clinical studies of transcutaneous electrical nerve stimulation (TENS) have used a variety of outcome measures to assess its effectiveness, with conflicting results. It is possible that TENS is effective on some measures of pain and not on others. The purpose of this study was to test the hypothesis that TENS reduces primary hyperalgesia of the knee induced by joint inflammation. ⋯ These data suggest that TENS inhibits primary hyperalgesia associated with inflammation in a time-dependent manner after inflammation has already developed during both acute and chronic stages.
-
Using a new animal model of postoperative pain we recently developed, we investigated whether the selective cyclooxygenase-2 (COX-2) inhibitor parecoxib sodium, and the analgesic tramadol hydrochloride, attenuated mechanical primary hyperalgesia induced by minor surgery on the rat tail. ⋯ We have shown that the hyperalgesia in our model of postoperative pain is responsive to treatment with the analgesic tramadol, but it is not responsive to the selective COX-2 inhibitor parecoxib at the doses we used.
-
Neuroimmunomodulation · Jan 2007
Role of histamine H3 and H4 receptors in mechanical hyperalgesia following peripheral nerve injury.
Histamine is a chemical mediator that acts at four known types of histamine receptors and has been widely implicated in the development of nociception and neuropathic pain. Blocking histamine H(1) and H(2) receptors has been shown to reduce hyperalgesia following nerve injury, but the role of histamine H(3) and H(4) receptors in neuropathic pain has not been studied. Here, we used blockers of histamine H(3) and H(4) receptors to assess their effects on neuropathic pain behavior and mast cell numbers following peripheral nerve injury. In addition, we assessed the effect of activating H(4) receptors on neuropathic pain behavior. ⋯ We propose that the increase in mechanical hyperalgesia produced by thioperamide and JNJ 7777120 and the decrease in mechanical hyperalgesia produced by VUF 8430 may represent a direct effect of these agents on mechanospecific primary afferents, or an indirect effect of these agents via injury-induced inflammation.
-
Randomized Controlled Trial Comparative Study
Placebo-controlled comparison of a morphine/dextromethorphan combination with morphine on experimental pain and hyperalgesia in healthy volunteers.
In this double-blind, placebo-controlled, crossover study we compared the analgesic effect of a single oral dose of 30-mg dextromethorphan and 30-mg morphine combination (MS/DM) to 30 mg morphine (MS) alone and either placebo or 30 mg dextromethorphan (DM) on cutaneous sensitization induced by heat/capsaicin (topical) sensitization on the forearm and the brief thermal sensitization model on the thigh in 22 healthy volunteers. Outcome measures were areas of secondary hyperalgesia to brush and von Frey hair stimulation in both sensitization models and the painfulness of acute thermal noxious stimulation on the upper arm. Compared with placebo, both MS/DM and morphine had some effect on the secondary hyperalgesia and reduced the painfulness of a noxious thermal stimulus. The analgesic effect of MS/DM was not superior to that of morphine on any outcome measure. These results differ from preclinical studies with animal experimental pain models in which DM markedly potentiated the analgesic effects of opioids, but they are in accordance with recent clinical trials for chronic pain. ⋯ Adding dextromethorphan to morphine (1:1 ratio) did not enhance analgesia on measures of experimental cutaneous sensitization and acute noxious thermal stimulation in healthy volunteers. The results differ from preclinical studies but agree with clinical trials. Human experimental models of pain and neuronal sensitization, which are responsive to oral opioids, allow efficient study of opioid combination analgesics and simplify the process for determining the optimal dose and/or dose ratio.