Articles: hyperalgesia.
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The present study was undertaken to determine the effects of intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) melatonin on mechanical allodynia and thermal hyperalgesia in mice with partial tight ligation of the sciatic nerve, and how the nitric oxide (NO) precursor l-arginine and the opiate antagonist naloxone influence this effect. A plantar analgesic meter was used to assess thermal hyperalgesia, and nerve injury-induced mechanical hyperalgesia was assessed with von Frey filaments. 1-5 weeks following the surgery, marked mechanical allodynia and thermal hyperalgesia developed in neuropathic mice. ⋯ These results suggest that although it has different effects on neuropathic pain-related behaviors, melatonin may have clinical utility in neuropathic pain therapy in the future. It is also concluded that l-arginine-NO pathway and opioidergic system are involved in the antihyperalgesic effect of melatonin in nerve-injured mice.
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Drug combinations have the potential advantage of greater analgesia over monotherapy. The present study was aimed to assess any possible interaction (additive or potentiation) in the antinociceptive effects of etoricoxib; a novel cyclooxygenase-2 inhibitor, and tramadol; a typical opioid agonist when administered in combination against mechanical hyperalgesia induced by spinal cord injury in rats. The nature of interaction was analyzed using surface of synergistic interaction (SSI) analysis and an isobolographic analysis. ⋯ The SSI was calculated from the total antihyperalgesic effect produced by the combination after the subtraction of the antihyperalgesic effect produced by each of the individual drug. In the isobolographic analysis, the experimental ED50 was found to be far below the line of additivity also indicating a significant (P < 0.05) synergistic antihyperalgesic effect when etoricoxib and tramadol was co-administered to rats. The synergistic antihyperalgesic effect of etoricoxib and tramadol combination suggests that these combinations may have clinical utility in mechanical hyperalgesia associated with spinal injury.
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Opioid analgesics are effective for treating many pain conditions. Opioid analgesic tolerance is a pharmacologic phenomenon that could affect the clinical use of opioid analgesics. ⋯ Thus, exposure to opioids could lead to two seemingly unrelated cellular processes (ie, the development of opioid tolerance and opioid-induced pain sensitivity). Their converging effects may be part of the mechanisms leading to the reduced opioid analgesic efficacy in chronic opioid therapy.
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Comparative Study
Erythropoietin reduces Schwann cell TNF-alpha, Wallerian degeneration and pain-related behaviors after peripheral nerve injury.
Chronic sciatic nerve constriction injury (CCI) induces Wallerian degeneration and exaggerated pain-like behaviors. These effects are mediated in large part by pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNF-alpha). In this study, we demonstrate that systemically administered recombinant human erythropoietin (rhEpo) facilitates recovery from chronic neuropathic pain associated with CCI in rats. ⋯ RhEpo inhibited TNF-alpha expression in response to lipopolysaccharide, supporting the conclusions of our in vivo CCI experiments. In addition, rhEpo directly counteracted Schwann cell death induced by exogenously added TNF-alphain vitro. These results indicated that rhEpo regulates TNF-alpha by multiple mechanisms; rhEpo regulates TNF-alpha mRNA expression by Schwann cells but also may directly counteract TNF-alpha signaling pathways that lead to injury, chronic pain and/or death.
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Comparative Study
Reliability of pain threshold measurement in young adults.
The objective was to examine reliability of pressure and thermal (cold) pain threshold assessment in persons less than 25 years of age, using intra-class correlation (ICC) and coefficients of repeatability and variability. We measured thresholds to pain from pressure algometry and ice placed at the hand and head in 10 healthy volunteers aged 18-25. Intra-rater reliability was examined with ICC. ⋯ Reliability of repeat assessments was high as assessed by ICC, although coefficients of repeatability and variation indicated considerable inter-individual variation in repeat measurements. Pressure algometry and strategically placed ice appear to be reliable techniques for assessing pain processing in young adults. Reliability studies employing ICC may benefit from complementary estimation of CR and CV.