Articles: hyperalgesia.
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Randomized Controlled Trial Clinical Trial
Postoperative morphine use and hyperalgesia are reduced by preoperative but not intraoperative epidural analgesia: implications for preemptive analgesia and the prevention of central sensitization.
The aim of this study was to evaluate the postoperative morphine-sparing effects and reduction in pain and secondary mechanical hyperalgesia after preincisional or postincisional epidural administration of a local anesthetic and an opioid compared with a sham epidural control. ⋯ Preincisional administration of epidural lidocaine and fentanyl was associated with a significantly lower rate of morphine use, lower cumulative morphine consumption, and reduced hyperalgesia compared with a sham epidural condition. These results highlight the importance of including a standard treatment control group to avoid the problems of interpretation that arise when two-group studies of preemptive analgesia (preincisional vs. postsurgery) fail to find the anticipated effects.
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Comparative Study
Antihyperalgesic and side effects of intrathecal clonidine and tizanidine in a rat model of neuropathic pain.
Although intrathecal clonidine produces pronounced analgesia, antinociceptive doses of intrathecal clonidine produce several side effects, including hypotension, bradycardia, and sedation. Intrathecal tizanidine, another alpha(2)-adrenergic agonist, has provided antinociception without producing pronounced hemodynamic changes in animal studies. However, it has been unclear whether antihyperalgesic doses of intrathecal clonidine and tizanidine produce hypotension and bradycardia in a neuropathic pain state. This study was designed to evaluate the antihyperalgesic effects and side effects of intrathecal clonidine and tizanidine in a rat model of neuropathic pain. ⋯ The antihyperalgesic dose of intrathecal clonidine and the antinociceptive doses produced several side effects. Intrathecal tizanidine at the dose that reversed hyperalgesia would be preferable for neuropathic pain management because of absence of hypotension and bradycardia and lower incidence of sedation.
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Comparative Study
A single dose of liposome-encapsulated oxymorphone or morphine provides long-term analgesia in an animal model of neuropathic pain.
An extended-release formulation of oxymorphone was produced by encapsulation into liposomes, using a novel technique. Liposome-encapsulated morphine was produced, using a standard technique These preparations were tested in an animal model of neuropathic pain. Male Sprague-Dawley rats (approx. 300 g) were allotted to control (non-loaded liposomes) and treatment (liposome-encapsulated oxymorphone or morphine) groups. ⋯ Non-ligated rats treated with liposome-encapsulated oxymorphone had a small, but significant increase in thermal withdrawal latency from day four through day seven. One subcutaneous injection of liposome-encapsulated oxymorphone or morphine was effective in preventing hyperalgesia in this pain model for up to seven days. These results suggest that liposome-encapsulation of oxymorphone offers a novel, convenient, and effective means to provide long-term analgesia.
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Comparative Study
Normal sensitivity to acute pain, but increased inflammatory hyperalgesia in mice lacking the nociceptin precursor polypeptide or the nociceptin receptor.
Nociceptin/orphanin FQ (N/OFQ) is the endogenous agonist of the N/OFQ peptide receptor (NOP receptor). It is released from a larger precursor polypeptide, called prepro-nociceptin (ppN/OFQ) from which, in addition to N/OFQ, other biologically active neuropeptides may be derived. Increasing evidence indicates that exogenous application of N/OFQ to the central nervous system of mice and rats induces pro- and antinociceptive effects depending on the dose and site of administration. ⋯ However, NOP-R-/-, ppN/OFQ-/- and double knockout mice showed markedly stronger nociceptive responses during prolonged nociceptive stimulation in the second phase of the formalin test and significantly lower thermal pain thresholds in inflamed tissue after zymosan A injection. These results indicate that N/OFQ contributes significantly to endogenous pain control during prolonged nociceptive stimulation but does not affect acute pain sensitivity. Among the three types of mutant mice nociceptive behaviour was nearly identical, indicating that the lack of other potential ppN/OFQ products in the ppN/OFQ-/- mice was apparently without effect on the nociceptive phenotype.
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Gabapentin, a gamma-aminobutyric acid analog anticonvulsant, has been shown to possess antinociceptive effects in animal models and clinical trials. An endogenous binding site of [3H]gabapentin has been revealed to be the alpha(2)delta subunit of voltage-dependent Ca2+ channels. Magnesium chloride, ruthenium red, and spermine have been shown to modulate [3H]gabapentin binding to this binding site in vitro. In this study, the authors examined whether intrathecal magnesium chloride, ruthenium red, or spermine could affect the antiallodynic effect of intrathecal gabapentin in a rat model of postoperative pain. ⋯ These results provide behavioral evidence to support that the alpha(2)delta subunit of Ca2+ channels may be involved in the antiallodynic action of intrathecal gabapentin in the postoperative pain model.