Articles: hyperalgesia.
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Randomized Controlled Trial
Effects of intraoperative high-dose vs low-dose remifentanil for postoperative epidural analgesia after gynecological abdominal surgery: a randomized clinical trial.
To evaluate whether intraoperative high-dose remifentanil infusion increased local anesthetic consumption in postoperative epidural analgesia and postoperative pain scores compared with low-dose remifentanil infusion. ⋯ Intraoperative high-dose remifentanil infusion increased local anesthetic consumption in postoperative epidural analgesia relative to low-dose remifentanil.
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The treatment of neuropathic pain remains a clinical challenge because of its unclear mechanisms and broad clinical morbidity. Matrix metalloproteinase (MMP)-9 and MMP-2 have previously been described as key components in neuropathic pain because of their facilitation of inflammatory cytokine maturation and induction of neural inflammation. Therefore, the inhibition of MMPs may represent a novel therapeutic approach to the treatment of neuropathic pain. ⋯ The administration of NAC blocked the maturation of interleukin-1β, which is a critical substrate of MMPs, and markedly suppressed the neuronal activation induced by CCI, including inhibiting the phosphorylation of protein kinase Cγ, NMDAR1, and mitogen-activated protein kinases. Finally, NAC significantly inhibited CCI-induced microglia activation but elicited no notable effects on astrocytes. These results demonstrate an effective and safe approach that has been used clinically to alleviate neuropathic pain through the powerful inhibition of the activation of MMPs.
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Review
Muscle Triggers as a Possible Source of Pain in a Sub-group of Tension Type Headache Patients?
Tension-type headache (TTH) is a common condition but the underlying etiology is not understood. Episodic TTH may develop into chronic TTH, and some possible triggers may be involved in generation and maintenance. Nociceptive generators and hyperexcitable spots in neck and shoulder regions may to some degree contribute to TTH. The current paper highlights some of the possible triggers and associated pain mechanisms involved in TTH and discusses whether inhibition of these possible triggers may provide new treatment options. ⋯ Understanding the possible triggers in TTH, muscle hyperalgesia, and widespread pain sensitization, may help to develop better management regimes and possibly prevent TTH from developing into more chronic conditions. Currently, there is a striking difference between the clinical observational studies favoring the role of muscle triggers in TTH and the intervention studies generally not supporting the role of muscle triggers in TTH.
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Oxidative stress is generated in several peripheral nerve injury models. Nuclear factor erythroid 2-related factor 2 (Nrf2) is activated to have a role in antioxidant effect. After nerve injury, the severely painful behavior is also performed. ⋯ Therefore, in this study, we compared the effects of Nrf2 antibody administration following sciatic nerve-pinch injury on painful behavior induced in young mice and neurochemical changes in dorsal root ganglion neurons. After pinch nerve injury, we found that the magnitude of the thermal allodynia was significantly decreased after application of Nrf2 antibody (5ul, 1mg/ml) in such injured animals and phosphorylated ERK(p-ERK) as well as the apoptotic protein (i.e., Bcl-6) in DRG neurons were also down-regulated in the anti-Nrf2-treated injured groups compared to the saline-treated groups. Taken collectively, these data suggested that the Nrf2 antibody reduced thermal hyperalgesia via ERK pathway and the down regulation of Bcl-6 protein from the apoptosis pathway might be protecting against the protein deletions caused by anti-Nrf2 effect and suggested the new therapeutic strategy with Nrf2 inhibitor following nerve injury.
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The transient receptor potential cation channel subfamily M 8 (TRPM8) agonist L-menthol has been used traditionally for its topical counterirritant properties. Although the use of topical L-menthol for pain is casuistically established, evidence regarding its efficacy is negligible. This study aimed to characterize the effect of L-menthol as a counterirritant on cutaneous pain and hyperalgesia provoked by topical application of the transient receptor potential cation channel, subfamily A, member 1 (TRPA1) agonist trans-cinnamaldehyde (CA). In a randomized, double-blinded study CA was applied to a 3 × 3-cm area of the volar forearm evoking neurogenic inflammation, pain, mechanical, and thermal hyperalgesia in 14 healthy volunteers. In different sessions, 10% CA alone or 40% L-menthol applied simultaneously with 10% CA were administered for 20 minutes, throughout which the subjects rated the pain intensity on a visual analogue scale of 0 to 10. Extensive quantitative sensory testing was conducted and superficial blood flow (neurogenic inflammation) was recorded. Administration of CA evoked spontaneous pain, neurogenic inflammation, thermal hyperalgesia, and primary and secondary mechanical hyperalgesia. Coadministration of topical L-menthol reduced spontaneous pain intensity (P < .01), neurogenic inflammation (P < .01), primary mechanical hyperalgesia (P < .05), secondary mechanical hyperalgesia (P < .05), and heat hyperalgesia (P < .05), but not cold hyperalgesia. L-menthol exhibited inhibitory effects on simultaneously established pain, hypersensitivity, and neurogenic inflammation in a human TRPA1-induced pain model. Potent TRPM8 agonists could be useful as topical antihyperalgesics. The study and the trial protocol is registered and approved by the local research ethics committee under the jurisdiction of the Danish Medicines Agency number N-20130005. The protocol also is registered at Clinicaltrials.gov under NCT02653703. ⋯ Drugs interacting with transient receptor potential channels are of great therapeutic potential. In the present study we established cutaneous pain and hyperalgesia using the TRPA1 agonist CA. Subsequently, we showed that the frequently used topical counterirritant and TRPM8 agonist, L-menthol, decreased evoked pain, hyperalgesia, and inflammation, indicating direct and indirect antinociceptive mechanisms.