Articles: hyperalgesia.
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Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological method for pain management. Commercial TENS units differ in their waveform characteristics. However, effects of different waveforms on analgesia produced by TENS are unknown. Therefore, we compared effects of high-frequency TENS with different waveforms--asymmetric biphasic square and symmetric biphasic square--on inflammatory hyperalgesia. Paw withdrawal latency to heat (PWL) was assessed prior to inflaming the knee joint with 3% carrageenan/kaolin in rats. Four hours after induction of inflammation, PWL significantly decreased in all groups, indicating development of hyperalgesia. High-frequency TENS was then applied to the inflamed knee joint for 20 minutes while the rat was lightly anesthetized with halothane. TENS treatment with either the asymmetric or symmetric waveform significantly increased the PWL when compared with sham TENS. Thus, differences in waveform characteristics do not affect the anti-hyperalgesia produced by TENS. ⋯ This study shows that different waveforms of TENS do not affect analgesic efficacy. This suggests that clinicians can select different waveforms to provide comfort during treatment but that reduction in pain is not a factor for waveform selection.
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Noxious C-fibre stimulation produces increased sensitivity within the injured area (primary hyperalgesia), and a surrounding zone of secondary hyperalgesia. As significant changes in nociceptive processing occur during development, we compared C-fibre induced primary and secondary hyperalgesia in rat pups aged 3, 10 and 21 postnatal (P) days. Hyperalgesia was measured by electromyography flexion reflex recordings following mustard oil or capsaicin at the site of (primary hyperalgesia), or distant to (secondary hyperalgesia) hindpaw mechanical stimuli. ⋯ These results provide evidence that primary and secondary hyperalgesia are differentially modulated during development. Furthermore, since ERK activation is required for secondary hyperalgesia, phosphoERK expression can be used to map the spatial distribution of neuronal activation in the spinal cord. Understanding changing responses to injury in the developing nervous system is important for clinical paediatric practice, and will enhance our ability to target the most effective site with a developmentally appropriate analgesic regime.
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Opioids have been successfully used for the management of acute and cancer-related pain. Concerns regarding side effects, tolerance, dependence, addiction, and hyperalgesia have limited the use of opioids for the management of chronic nonmalignant pain. This article will review updated information from both clinical and preclinical studies regarding opioid-induced hyperalgesia, tolerance, and dependence. The implications of these issues in clinical opioid therapy also will be discussed.
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Clinical Trial
Gabapentin activates spinal noradrenergic activity in rats and humans and reduces hypersensitivity after surgery.
Gabapentin has been reported to inhibit various acute and chronic pain conditions in animals and humans. Although the efficacy of gabapentin depends on the alpha2delta subunit of voltage-gated calcium channels, its analgesic mechanisms in vivo are still unknown. Here, the authors tested the role of spinal noradrenergic inhibition in gabapentin's analgesia for postoperative pain. ⋯ These data suggest that gabapentin activates the descending noradrenergic system and induces spinal norepinephrine release, which produces analgesia via spinal alpha2-adrenoceptor stimulation, followed by activation of G protein-coupled inwardly rectifying potassium channels. The authors' clinical data suggest that gabapentin activates the descending noradrenergic system after preoperative oral administration at the time of surgery. These data support a central mechanism of oral gabapentin to reduce postoperative pain and suggest that this effect could be magnified by treatments that augment the effect of norepinephrine release.
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Recently, it has been appreciated that in addition to their antinociceptive properties, opioid analgesics also can enhance pain sensitivity (opioid-induced hyperalgesia [OIH]). OIH may enhance preexisting pain and contribute to dose escalation, tolerance, and misuse/abuse of opioids. Better information is needed to determine which opioid or opioid combinations may be least likely to produce OIH and therefore possibly represent better choices for pain management. Herein the authors have examined the hyperalgesic and antinociceptive properties of racemic methadone and its enantiomers alone and in combination with morphine in rats. Methadone is of particular interest because it possesses both micro-receptor agonist and N-methyl-d-aspartate receptor antagonist activities. ⋯ The current findings with methadone are supportive of previous findings implicating mu-opioid and N-methyl-d-aspartate receptor mechanisms in OIH. Better understanding of OIH may help in choosing the most appropriate opioids for use in the treatment of pain.