Articles: hyperalgesia.
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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.
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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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Anesthesia and analgesia · Jun 2003
The effect of systemic zonisamide (Zonegran) on thermal hyperalgesia and mechanical allodynia in rats with an experimental mononeuropathy.
We studied the ability of zonisamide (Zonegran) to relieve thermal hyperalgesia and/or mechanical allodynia in the chronic constriction injury model of neuropathic pain. Zonisamide (25, 50, or 100 mg/kg) or saline was administered in a blinded, randomized manner by intraperitoneal injection on postoperative days (PODs) 4, 5, and 6. Paw withdrawal latency (PWL) to heat, paw withdrawal response to von Frey monofilaments, and pain scores based on weight-bearing were tested: before surgery; before and after zonisamide or saline (PODs 4, 5, and 6); and on POD 9. Systemic zonisamide relieved thermal hyperalgesia in a dose-dependent manner. All PWLs were significantly increased after zonisamide administration compared with pre-zonisamide measurements, except with the 100 mg/kg dose on POD 5. After zonisamide 100 mg/kg administration, there was a sustained increase in PWL on PODs 5 and 9, with significant carryover effect from the previous dose. However, zonisamide had little effect on mechanical allodynia, except at the 100 mg/kg dose, which was sedating in the rat. At the 100 mg/kg dose, paw withdrawal response was increased on PODs 4 and 5, whereas pain scores were reduced on PODs 4, 5, and 6. Pain scores were inconsistently reduced after 50 mg/kg or 25 mg/kg doses. ⋯ Zonisamide causes a dose-related decrease in heat sensitivity in a rat model of neuropathic pain, but relieves mechanical sensitivity only in a dose that is sedating to the rat. Zonisamide may be useful in the treatment of some types of neuropathic pain.
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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.