Articles: hyperalgesia.
-
We report a case of a patient with metastatic testicular cancer and intractable pain refractory to massive doses of oral, intravenous, and intrathecal (IT) opioids supported by analgesic adjuvants. During our efforts to control his pain, the patient exhibited opioid-induced hyperalgesia, an uncommon but important phenomenon seen with high-dose opioid therapy. With appropriate opioid adjustment--in this case reduction of intrathecal morphine dosage by a factor of 100--the condition rapidly resolved and the patient became pain-free and remained so until his death six weeks later. The keys to identifying this uncommon, but treatable, opioid side effect are recognizing it as a possibility when aggressive efforts to control pain with high doses of opioids, especially when administered neuraxially, are met with increasing pain.
-
Joint manipulation has long been used for pain relief. However, the underlying mechanisms for manipulation-related pain relief remain largely unexplored. The purpose of the current study was to determine which spinal neurotransmitter receptors mediate manipulation-induced antihyperalgesia. ⋯ NAN-190 also blocked manipulation-induced antihyperalgesia suggesting that effects of methysergide are mediated by 5-HT1A receptor blockade. However, spinal blockade of opioid or GABAA receptors had no effect on manipulation induced-antihyperalgesia. Thus, the antihyperalgesia produced by joint manipulation appears to involve descending inhibitory mechanisms that utilize serotonin and noradrenaline.
-
J. Pharmacol. Exp. Ther. · Oct 2003
Evidence for an involvement of supraspinal delta- and spinal mu-opioid receptors in the antihyperalgesic effect of chronically administered clomipramine in mononeuropathic rats.
The mechanisms of involvement of the opioidergic system in the antinociceptive effect of antidepressants remain to be elucidated. The present study was designed to determine what type of opioid receptors may be involved at the spinal and supraspinal levels in the antihyperalgesic effect of clomipramine, a tricyclic antidepressant commonly prescribed in the treatment of neuropathic pain. Its antihyperalgesic effect on mechanical hyperalgesia (paw pressure test) in rats induced by chronic constriction injury of the sciatic nerve was assessed after repeated administrations (five injections every half-life, a regimen close to clinical use). ⋯ The effect was inhibited by intrathecal administration of CTOP and intracerebroventricular administration of naltrindole, whereas nor-BNI was ineffective whatever the route of injection. These results demonstrate a differential involvement of opioid receptors according to the level of the central nervous system: delta-receptors at the supraspinal level and mu-receptors at the spinal level. Clomipramine could act via a neuronal pathway in which these two receptors are needed.
-
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.
-
Cannabinoid receptor agonists inhibit inflammatory hyperalgesia in animal models. Nonselective cannabinoid receptor agonists also produce central nervous system (CNS) side effects. Agonists selective for CB2 cannabinoid receptors, which are not found in the CNS, do not produce the CNS effects typical of nonselective cannabinoid receptor agonists but do inhibit acute nociception. The authors used the CB2 receptor-selective agonist AM1241 to test the hypothesis that selective activation of peripheral CB2 receptors inhibits inflammatory hyperalgesia. ⋯ Local, peripheral CB2 receptor activation inhibits inflammation and inflammatory hyperalgesia. These results suggest that peripheral CB2 receptors may be an appropriate target for eliciting relief of inflammatory pain without the CNS effects of nonselective cannabinoid receptor agonists.